En esta memoria se presenta la Tesis Doctoral que lleva por título: DESARROLLO DE UNA PLATAFORMA DE TILLING EN MELÓN (Cucumis melo L.) Escrita por Mireia González To Director: Jordi Garcia Mas Tutora: Mª Carme Espunya Esta Tesis ha sido realizada en el Programa de Genòmica i Biotecnologia del IRTA que pertenece al Centre de Recerca en Agrigenòmica (CRAG) y dentro del programa de doctorado del Departamento de Bioquímica de la UAB. A Enero de 2014 T T A la meva mare que mha ensenyat a estimar i a mantenir lalegria "Dijo Tennyson que si pudiéramos comprender una sola flor sabríamos quiénes somos y qué es el mundo" Jorge L. Borges Ara tot just intento pensar en el principi d’aquesta aventura i me n’adono que jo era una persona totalment diferent. Els agraïments moltes vegades es queden curts, les paraules tants cops no poden copsar tot el que ha significat un gest o la companyia d’una persona. Per això vull començar dient que, segurament, aquestes paraules mai diguin tot el que volen dir. Aquest només és un intent de reconèixer i sobretot, agrair-vos a tots els que m'heu acompanyat en aquesta aventura de 8 anys. En primer lloc vull agrair a les persones que han fet possible aquest periple: a la Carme Espunya per ser la professora que em va descobrir el meu amor científic cap a les plantes. Al Jordi Garcia-Mas per confiar en una estudiant de pràctiques que arribava a l'IRTA de Cabrils amb moltes ganes d’aprendre i al Pere Arús per recolzar-lo en aquesta decisió. Vull agrair als que han col.laborat en aquest projecte perquè sense ells no s'hagués pogut dur a terme: a Fitó i al COMAV. En especial a la Belén Picó per aconseguir publicar un article d'aquest treball amb la seva dedicació i persistència. L'època a l’IRTA ha estat un dels períodes més feliços de la meva vida. Tots els que hi éreu hi vau contribuir; cadascú a la seva manera i durada. Els becaris (Edu (i les guerres privades d'aigua al laboratori quan ja no hi quedava ningú), Ibo, Iria, Juan (¡Ánimo, ya no queda nada!), Julio, Alí, Claudio, Roger, Eudald...). A tots ells els hi agraeixo la companyia, el fet de poder compartir la mica de desesperació que tantes vegades pateix un becari i poder riure dels nostres errors. Si un no s'equivoca, no aprèn. Des d’aquí, d'aquest petit espai meu i propi, vull fer un reconeixement a tots els tècnics, sense vosaltres els laboratoris no avançarien. És d'aquestes coses que tothom sap, però que crec que a vegades cal dir en veu alta i clara. Ells són: Fuensi (gràcies per ensenyar-me tant i per tenir tanta paciència amb el nostre estimat LICOR), Àngel (gràcies per la teva disposició i la teva alegria incondicional) Joana, Ana, Patricia, Alicia, Dani, Manoli... En especial a la Vane, sempre al meu costat, inseparables companyes de "poyata". Gràcies per fer-me riure (i a vegades fer-me plorar), per fer-me ballar i treballar, per ensenyar-me les tècniques i perquè fora de la feina m’has cuidat igual que cuides als teus. Gràcies per fer-me sentir tan estimada. Als companys de caseta (Montse, Francesc, Olga, Ainoha, Jonatan...) perquè allà vam ser autodidactes, vam compartir cafès i coneixements. Potser la ciència no cal que sigui tan seria, a vegades. A la Puri, pel “cachondeo” que m’animava les tardes com a gairebé ningú, encara que li trepitgés els "fregaos". A tots els investigadors (Werner, Jordi, Amparo, Momo, Montse M., Montse S., Wim, Txose, Gisela, Torben, Toni M.) i especial al Mourad per ensenyar-me que la ciència pot ser molt creativa, plena de colors inesperats (¡Esa eterna discusión con el salmón de los geranios!) i, sobretot, per acompanyarme en tantes tardes i nits de petita solitud a Arenys en les que em cuinaves cous-cous i peix al forn com si fos la seva pròpia germana. Al Santi Vilanova, perquè sempre m'ha cuidat i perquè en els moments que queia ell sempre m'oferia la mà per ajudar-me a aixecar. A la Marta Pujol, no només per tot el que l’admiro com a professional i el que he après amb ella, sinó també com a persona. Marta, sense tu, segur, que no hagués acabat aquest projecte. Gràcies Marta. Un dels aventatges que té la investigació és que et permet viatjar i fer estades a laboratoris d’altres països. A Evry vaig poder treballar al costat de l'Abdelhafid Bendahmane al qui vull agrair l’ensenyament de la tècnica del TILLING. També a la Christelle Troadec, amb qui vam compartir hores d'aprenentatge, llargues xerrades en franco-català-anglès i molts caramels. Merci beaucoup Christelle. La estancia en Evry fue como un "mini Erasmus" gracias a dos latinos: Nilo y Silvia. A ellos quiero agradecer que me acogieron en su piso como una más, me cocinaron a la italiana y me prepararon Pisco-Sour para olvidarnos entre todos de los diseños de cebadores y de las plantas de tomate. Nilo y Silvia siempre os recuerdo, gracias. A pesar de haber acabado las prácticas de doctorado en Marzo de 2010 y de no haber presentado la tesis, conseguí una beca en Italia, más concretamente en Roma para trabajar con Giovanni Giuliano en el ENEA. Considero ese período como una ampliación del doctorado y de mi aprendizaje. Per questo non vorrei lasciare di ringraziare a Marco, Silvia, Killy, Sara, Patrizia, Elio (DT!) e Giulia l'incredibile esperienza di vivere e lavorare a Roma. Lavorare divertendomi così tanto: ballare e bere la birra in laboratorio con Silvia al termine di lunghe giornate di lavoro tra i pomodori e PCR. Grazie a Giuliano per la fiducia in me e nelle mie capacità. E a tutti per rendere questo periodo uno dei giorni più felici della mia vita. Voglio tanto bene all'Italia e gli italiani!. Finalment i no menys important, vull agrair als amics que m’acompanyeu des de sempre i que m'heu vist créixer i madurar en aquest projecte. Que heu aguantat les llargues i constants (i segurament pesades ;-) converses sobre aquest tema i sempre heu confiat en mi. Crec que si confies en algú aquella persona també confia més amb ella mateixa per això vull dir-vos que és un regal preciós el que m'heu fet: Club Bikini (Marta, Anna P., Anna A.), PSFs!! (Martina, Jess, Raquel B. -gràcies també pel increïble disseny de la portada, sabia que faries alguna cosa que la sentiria pròpia, gràcies artista!- Raquel Ll., Nayibe, Isa, Nurieta, Alba, Tere...), Claudia sempre aprop estiguis on estiguis, Humanistes! (Marta, Eva, Laia) que m'heu acompanyat i juntes hem descobert tantes coses fantàstiques de la vida com per exemple que el coneixement és poder. Sou totes fantàstiques, dones increïbles. Us admiro a totes i de totes he après lliçons imprescindibles per créixer. Sou l'orgull del gènere femení! ;-). Al Jordi Carreras perquè sense ell probablement mai hagués iniciat aquesta aventura. Gràcies per ajudar-me tant a creure en mi. I a tants amics que sempre em feu riure, pensar, imaginar, crear, superar-me: Jorge, Aleix, Belén, La Peña!!!, Carme, Manolo, Chelo, Marisa, Alexis...Papa, gràcies per ensenyar-me la disciplina, la constància i el sacrifici que han estat realment indispensables per projectes com aquest. Per acabar, vull agrair a la meva família tot l'esforç que han fet des de sempre i sobretot perquè sou els meus fans incondicionals i em cuideu com ningú. Mama no tinc paraules, ets fantàstica, la meva heroïna sense dubte. Marc, simplement t'adoro. Àvis (Eulàlia i Quimet) sou el meu exemple a seguir, no he conegut persones més bones que vosaltres. Patrick, tempiternament, gràcies per TOT, per la VIDA i per ensenyar-me que si un vol pot aconseguir els seus somnis. Nada por obligación, todo por ilusión. Gràcies, Gracias, Grazie, Thanks, Merci, Mireia González To Barcelona, 07/01/2014 T ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,. ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,0 .,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,2 .,.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,2 E@E@E@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@I E@E@F@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@I E@E@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@J E@E@H @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@L E@E@I @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ED E@E@I@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ED C!-!0%+71(#,0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ED C/!+0&,/*!#(:+%+71(#!@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EE C0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EF C0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EF C(#/,*!1/(#%0$%@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EG C @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EG E@E@I@F@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EH E@E@I@GA @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EH .,/,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.3 E@F@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EJ E@F@E@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EJ C @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EK @E%"($,0!)!0&,/*!01!21,*7/(#!0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EK @F +0%/#(,+%04$%)%#(,+%0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EL C @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EL @E%0!*(+!#(:+@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EL @F%0-2/(+(5!#(:+@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EM @G3($!#(:+@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EM .,0,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,/- E@G@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FD E@G@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FD E@G@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FE E@G@G@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FF C!0%0!+6),'!0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FF C'%+1%0.28*(#,0*,$(&(#!$,/%0$%"!0%0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FG C'%+1%0(+1%/#!)!+1%0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FH E@G@G@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FH C!$(!#(,+%0%)%#1/,*!'+71(#!0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FH C!$(!#(,+%0(,+(5!+1%0@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FH E@G@G@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FJ C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FJ CAB$%1/!+0&%/%+#(!C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FJ C @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FJ C21!'7+%0(0$(/('($!@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FK .,1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,/6 E@H@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@FM E@H@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@GD E@H@F@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@GF E@H@F@F@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@GI E@H@F@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@GJ E@H@F@H @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@HE E@H@F@I @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@HG .,2,,,,,,,,,,,,,,,13 E@I@E B(1,%+,%0!12/!0!C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@HJ E@I@F$B HC4!"$@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@HL E@I@G E@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@II ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,3. /,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,30 +,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,30 /,.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,30 F@E@E BDC@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@JG F@E@F EF@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@JI F@E@F@E E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@JI F@E@F@F F@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@JJ F@E@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@JJ F@E@G@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@JJ F@E@G@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@JK F@E@G@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@JL /,/,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,36 F@F@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KD F@F@E@E BC@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KD F@F@E@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KE F@F@E@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KF F@F@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KF F@F@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KF F@F@G@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KG F@F@H @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KG F@F@I @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KH F@F@I@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KH F@F@I@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KH F@F@I@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KH F@F@J @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KI F@F@J@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KI F@F@J@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KJ F@F@J@G ? @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KK F@F@K @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@KM F@F@L @@@@@@@@@@@@@@@@@@@@@KM /,0,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,5- F@G@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@LD F@G@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@LD +,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,5. /,1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,5. /,2,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,5. F@I@EB C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@LE F@I@F 0BC@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@LF F@I@G 0 @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@LG /,3 ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,50 F@J@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@LH F@J@F B C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@LH 0,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,54 0,.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,54 G@E@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@LK G@E@E@E JFAEEG@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@LK G@E@E@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@MD G@E@E@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@MF G@E@E@H @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@MG G@E@E@H@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@MG G@E@E@H@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@MH G@E@E@H@G @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@MH G@E@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@MK 0,/ ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,66 G@F@E B C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EDD G@F@E@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EDE G@F@E@F > @@@@@@@@@@@@@@@@@@@@@@@@EDI G@F@E@G GLHEEEI@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EDL G@F@F$B C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EEG G@F@F@E > $ @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EEH G@F@F@F G$@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EEK G@F@G!"$B HC@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EFE G@F@G@E > @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EFG G@F@H#B EC@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EFG G@F@H@E > @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EFH G@F@I @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EFI 0,0 %,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,./5 G@G@E #, $@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EFL G@G@F #, #@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EGJ 0,1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.1- G@H@E @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EHE G@H@F @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EHF G@H@G@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EHG G@H@H @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EHI 1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.22 1,.,,,,,,,,,,,,,,,,,.22 1,/,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.3. H@F@E B C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EJE H@F@F% HB HC@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EJF H@F@G!"$@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EKD H@F@H#B C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EKE H@F@I @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EKF 1,0 %,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.41 H@G@E% HB C@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EKH H@G@F#B EC@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@EKL 1,1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.50 ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.56 #$#%"&!',,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.6/ ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,/.. ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,/16 ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,/24 T TTTTT m '%30mGYG[m09$'!-m!-,m*-1m.0',!'.*#1m.0-"3!2-0#1m"#m+#*A,mm,'4#*m+3,"'*YYmYYYYYYYYYYYYYYYYYYYYYYYYYYmMm '%30mGYH[m09$'!-m"#m*-1m.>1#1m!-,m+91m#6.-02!'A,m"#m+#*A,mm,'4#*m+3,"'*mmYYYYYYYYYYYYYYYYYYYYYYYmNm '%30mGYI[m$#!2-m"#*mmm,'4#*m+-*#!3*0mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmHIm '%30mGYJ[m0-2-!-*-m#+.*#"-m.0m#*m+<2-"-m"#mmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmIHm '%30mGYK[m#2#!!'A,m"#m3,m+32!'A,m#,m3,m.- *!'A,m"#mm#,m+#*A,m#,m3,m%#*m"#m !0'*+'"m4#02'!*m"#mjmJIFFYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmINm '%30mGYL[m(#+.*-m"#m!304m"#m"'1-!'!'A,m"#m$0%+#,2-1m+.*'$'!"-1m7m0#,230*'8"-1YmYmJFm '%30mGYM[m32m"#m1>,2#1'1m"#m!0-2#,-1m#,m.*,21YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmJMm '%30mGYN[m#.0#1#,2!'A,m"#*m1'12#+m"#m0#1'12#,!'m#,m.*,21m 1"-m#,m*m',2#0!!'A,m%#,j j%#,m^*-0ZmGOMG_YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmJOm '%30mGYO[m3,!'-,+'#,2-m"#*m','!'-m"#m*m20"3!!'A,mmmmmmmmmmmmmmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmKHm '%30mGYGF[m3,!'-,#1m.-123*"1m.0m#*mI#-)J>YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmKKm '%30mGYGG[m1/3#+m"#*m!'!*-m"#m,%mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmKLm '%30mGYGH[m1/3#+m"#*m;mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmKMm '%30mHYG[m0-!#"'+'#,2-m.0m- 2#,#0m#*mm"#m*m.- *!'A,m"#mYmYYYYYYYYYYYYYYYYYYYYYYYYYYmLLm '%30mHYH[m'1#@-mm"#m*1m.*!1m.--*YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmLMm '%30mHYI[m1/3#+m"#*m.0-2-!-*-m"#mmmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmMIm '%30mHYJ[m-,2(#m%#*mjJIFFmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmMLm '%30mHYK[m'13*'8!'A,m"#m*1m+3#1201m#,m#*m%#*m"#mYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmMMm '%30mHYL[m*,2'**m.0m*m"#!-,4-*3!'A,YYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmMNm '%30mIYG[m-1'!'A,m"#m*-1m1m,*'8"-1m#,m*m*>,#mLHjGGIYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmOFm '%30mIYH[m-0!#,2(#1m"#m%#0+',!'A,YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmOGm '%30mIYI[mm1/3#+m"#*m$0%+#,2-m1#!3#,!'"-m"#*m%#,m>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmOKm '%30mIYJ[m1/3#+m"#m*m0#%'A,m"#mm"#m+#*A,mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFHm '%30mIYK[m#!3#,!'m.0-2#'!m"#*m%#,m"#m*mm#,m+#*A,mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFIm '%30mIYL[m0 -*m$'*-%#,<2'!-m"#*m%#,m"#m*mm"#m+#*A,mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFJm '%30mIYM[m1/3#+m"#*m$0%+#,2-m"#m*mm,*'8"-m+#"',2#mYmYYYYYYYYYYYYYYYYYYYYYYYYYYmGFKm '%30mIYN[m0-+2-%0+1m"#m*1m"-1m$+'*'1m!-,m+32!'-,#1m#,m*m8-,m#6A,'!m"#m*m mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFLm '%30mIYO[m#.0#1#,2!'A,m"#m*m.02#m1#!3#,!'"m"#m*mmYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFMm '%30mIYGF[m#.0#1#,2!'A,m"#m*-1mHFm+',-9!'"-1YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFNm '%30mIYGG[m+%#,m"#m20#1m$032-1m"#m.*,21mHmmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFOm '%30mIYGH[m*9,23*1mHm"#m*m$+'*'m+32,2#mINJYYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGGm '%30mIYGI[m0-+2-%0+1m"#m*mmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGHm '%30mIYGJ[m#.0#1#,2!'A,m"#*m%#,m>m#,m+#*A,m^(-0_YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGIm '%30mIYGK[m0 -*m$'*-%#,<2'!-m"#*m%#,m>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGJm '%30mIYGL[m*',#+'#,2-m#,20#m*1m.0-2#>,1m"#m>m7m#*mI#-)J>m"#m+#*AmmYYYYYYYYYYYYYYYYYYYYYYYYmGGLm '%30mIYGM[m-"#*(#m"#m*m.0-2#>,m>m"#*m+32,2#mHYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGNm '%30mIYGN[m-"#*(#m"#m*m.0-2#>,m>m#,mIm!-,m.-1' *#m*'%,"-m^+-*<!3*mKdm"#*m +_YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGNm '%30mIYGO[m-"#*(#m"#m*m.0-2#>,m>m#,mIm+#"',2#m#*m/.*/.O"#*m.0-%0+m7m"#*m +32,2#mKYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGOm '%30mIYHF[m/.*/.O"#*m.0-%0+m7m"#*m+32,2#mKmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGOm '%30mIYHG[m-"#*(#m"#m*m.0-2#>,m>m#,mIm+#"',2#m#*m32.32m"#*m.0-%0+m7m "#*m+32,2#mNmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHFm '%30mIYHH[m-"#*(#m"#m*m.0-2#>,m>m#,mIm+#"',2#m#*m/.*/.O"#*m.0-%0+m7m"#*m +32,2#mOmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHFm '%30mIYHI[m-"#*(#m"#m*m.0-2#>,m#,mIm"#*m%#,m>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHGm '%30mIYHJ[m1/3#+m"#*m%#,mI#-)J>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHHm '%30mIYHK[m0 -*m$'*-%#,<2'!-m"#*m%#,mI#-)J>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHIm '%30mIYHL[m1/3#+m"#*m%#,m;mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHIm '%30mIYHM[m0 -*m$'*-%#,<2'!-m"#*m%#,m;mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHJm '%30mIYHN[m#*m"#m!-m.0m#*m.0'+#0m+.*'!A,m"#m>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHOm '%30mIYHO[m0-+2-%0+m"#m*1m40'#""#1mJMJm7mLHjGGImYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGIFm '%30mIYIF[m#*m"#m!-m.0m#*m1#%3,"-m+.*'!A,m"#m>YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGIIm '%30mIYIG[m0-+2-%0+1m"#mLHjGGIm7mmKFKLFHYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGILm '%30mIYIH[m#*m"#m!-m.0m#*m+.*'!A,m"#*m%#,m;mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGIMm '%30mIYII[m0-+2-%0+m"#*mmGm"#*m.0'+#0m#6A,m"#*m%#,m;mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGINm '%30mIYIJ[m0-!#"'+'#,2-m.0m*m1#*#!!'A,m"#m+#*-,#1m!-,m$#,-2'.-1mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGJJm '%30YJYG[m*9,23*m!-,m$#,-2'.-m* ',-mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGLHm '%30mJYH[m*',#+'#,2-m+#"',2#m&/-.&m"#m*m.0-2#',m#JmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGLJm '%30mJYI[m/.*/.O"#*m.0-%0+mm"#*m%#,m#JmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGLMm '%30mJYJ[m*',#+'#,2-m+#"',2#m*312*m"#m>m7mI#-)J>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGMGm '%30mJYK[m0"3!!'A,mm.0-2#>,m"#*m+m"#*m%#,m#JYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGMMm '%30mJYL[m1203!230m"#m*-1m"-+','-1m'"#,2'$'!"-1m#,m;m"#m,#)*-#-mYYYYYYYYYYYYYYYYYYYYYYYYYYYmGMNm '%30mJYM[m*',#+'#,2-m+B*2'.*#m"#m*-1m%#,#1m;m#,m,#)*-#-Zm2-+2#m7m+#*A,m7m*-1m %#,#1m>Fm?m7mm"#m2-+2#YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGNGm '%30mJYN[m!!#1'-,#1m#,m*1m/3#m1#m&,m"#2#!2"-m#*mmGmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGNHm '%30mJYO[m,$-0+!'A,m"'1.-,' *#m#,m*m 1#m"#m"2-1m" mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGNJm '%30mJYGF[m#,-2'.-1m"#m$032-m',2#0#1,2#1mm,'4#*m!-+#0!'*mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGNKm '%30mJYGG[m#,-2'.-1m'"#,2'$'!"-1m#,m.*,2m#,m-201m.- *!'-,#1m"#mYmYYYYYYYYYYYYYYYYYYmGNMm '%30mJYGH[m#,-2'.-1m'"#,2'$'!"-1m#,m$032-m#,m-201m.- *!'-,#1m"#mmmYYYYYYYYYYYYYYYYYYYYYmGNNm m *mGYG[m#.0#1#,2!'A,m"#m*1m$-0+1m232-+<0'!1mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGMm *mGYH[m#13+#,m"#m*-1m+329%#,-1m+91m& '23*#1mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmHHm *mGYI[m- *!'-,#1m"#mm"#100-**"1m#,m,'+*#1m7m.*,21mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmIJm *mHYG[m-1'1m"#mm32'*'8"1m.0m+320m*m.- *!'A,mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmLJm *mIYG[m-!*'8!'A,m"#m1YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmNNm *mIYH[m-1'1m"#mm31"1m.0m+320m*1m1#+'**1YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmOHm *mIYI[m *m!-+.02'4YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmOJm *mIYJ[m2-1m32'*'8"-1m.0m- 2#,#0m*1m1#!3#,!'1m"#m*-1m%#,#1m!,"'"2-1mYYYYYYYYYYYYYYYYYYYYYmGFFm *mIYK[m32,2#1m#,!-,20"-1m#,m#*m$0%+#,2-m"#mGGNNm. m"#*m%#,mmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFMm *mIYL[m#0+',!'A,m"#m*m1#+'**1mHm#,m*1m$+'*'1mINJm7mGGGKYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGFOm *mIYM[m#13*2"-1m"#m*m1#%0#%!'A,m"#m*m+32!'A,m#,m*1m$+'*'1m+32,2#1m"#m*mYYmGGHm *mIYN[m32,2#1m"#*m.0'+#0m"#*m%#,m>YYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGKm *mIYO[m32,2#1m#,m#*m1#%3,"-m+.*'!A,m"#*m%#,m>YYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGGKm *mIYGF[m0!2#0>12'!1m"#*m+32,2#m#,!-,20"-m#,m#*m%#,mI#-)J>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHIm *mIYGG[m$'!'#,!'m"#m+32!'A,m"#m.- *!'-,#1m"#mm+#*A,YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHKm *mIYGH[m11m"#m+32!'A,m"#mm"#*mm7m#*mYmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGHMm *mIYGI[m1m"#2#!2"-1m#,m#*m.0'+#0m+.*'!A,m"#*m%#,m>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGIGm *mIYGJ[m1m"#2#!2"-1m#,m#*m1#%3,"-m+.*'!A,m"#mO>mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGIJm *mIYGK[m.*-2'.-1m#,!-,20"-1m+#"',2#m#*m,9*'1'1m.-0m!-mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGIKm *mIYGL[m-*'+-0$'1+-1m"#2#!2"-1m#,m#*m.0'+#0m#6A,m"#*m%#,m;mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGINm *mIYGM[m *m!-,m*-1m&.*-2'.-1m"#2#!2"-1m.0m#*m%#,m;mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGIOm *mIYGN[m-0!#,2(#1m"#m%#0+',!'A,m#,m*1mJFFm$+'*'1mHm- 1#04"1YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGJGm *mIYGO[m#,-2'.-1m#,!-,20"-1m#,m#12"'-m"#m.*9,23*mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGJHm *mIYHF[m#,-2'.-1m#,!-,20"-1m#,m#12"'-m"#m.*,2m"3*2mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGJIm *mIYHG[m#,-2'.-1m#123"'"-1m#,m$032-1mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGJKm *mJYG[m-0!#,2(#m"#m 1#1m131!#.2' *#1m*m+329%#,-mmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGKMm *mJYH[m *m0#13+#,m"#m*-1m+32,2#1m#,!-,20"-1m#,m!"m.- *!'A,mYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGKOm *mJYI[m#13*2"-1m"#*m#123"'-m"#m1#%0#%!'A,m"#*m%#,m#JmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGLOm *mJYJ[m *m!-+.02'4m"#m*-1m.-*'+-0$'1+-1m!-YmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGMKm *mJYK[m#,-2'.-1m"#m*1m!!#1'-,#1m/3#m.0#1#,2,m#*mGmYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYmGNHm T TTT m [m!'"-m#1-6'00' -,3!*#'!-m [m+.*'$'#"m0%+#,2m#,%&2m-*7+-0.&'1+m [m!2#0'*m02'$'!'*m&0-+-1-+#m [m1'!m-!*m*'%,+#,2m#0!&m--*m [m-"-,1m.2'+'8#"m2-m'1!-4#0m#*#2#0'-31m#1'-,1m [m#,20-m"#m-,1#04!'A,m7m#(-0m"#m*m%0-"'4#01'""m*#,!',m [m#,20#m"#m#!#0!m#,m%0'%#,A+'!Zm0!#*-,m >[m!2-0m"#m','!'!'A,m"#m*m20"3!!'A,mJm [m2'*m#2,-m3*$-,2-m [m6.0#11#"m#/3#,!#m%m [m2&7*#,#m#!#.2-0m [m--"m,"m%0'!3*230#m0%,'82'-,m [m>,#1m- *#m.*-'"#1m [m','12#0'-m"#m%0'!3*230Zm#1!m7m*'+#,2!'A,Ym [m#*-,m#!0-2'!m.-2m'031m F[m#+'**1m+32%#,#'8"1m.0m%#0+',0m7m.0-"3!'0m*m%#,#0!'A,mGm G[m0'+#0m%#,#0!'A,m"#m.*,21m!0#!'"1mm.02'0m"#m*1m1#+'**1mFm H[m#%3,"m%#,#0!'A,m"#m.*,21m!0#!'"1mm.02'0m"#m*1m1#+'**1m"#m*1m.*,21mG [m2'-,*m#,2#0m$-0m'-2#!&,-*-%7m,$-0+2'-,m 1[m>,#1m!1'm1-%<,'!1m^#0m1-%#,'!m',#1_mm . [m.0#1m"#m 1#1m [m#!!'A,m#,m!"#,m"#m*m.-*'+#01m^-*7+#01#m&',m#!2'-,_m [m'2-#,-m#12301m [mmGLGIMKm&-,%5,m&0+'m [m'#*m"#m.-mGGGm [m3,2'22'4#m0'2m-!31m [m,"-+m+.*'$'#"m-*7+-0.&'!mm [m#120'!2'-,m0%+#,2m#,%2&m-*7+-0.&'1+m [m-02',%m,2-*#0,2m0-+m-*#0,2m [m',%*#m3!*#-2'"#m-*7+-0.&'1+m [m'+.*#m#/3#,!#m#.#2m [m0%#2',%m,"3!#"m-!*m#1'-,1mm#,-+#1m [m,'2<m"#m#!&#0!&#m#,m<,-+'/3#m<%#2*#Zm407m^0,!'_m G m Hm T m *m20 (-m"#1!0'2-m#,m#12m2#1'1m"-!2-0*m1#m#,+0!m"#,20-m"#*m.0-7#!2-mm ^HFGIjHFHIMZm HFFJjHFFM_m 3,-m "#m !37-1m - (#2'4-1m #0m *m !-,1203!!'A,m "#m 3,m .*2$-0+m"#mm#,m+#*A,Ym m "'1.-,' '*'""m "#m 0#!301-1m %#,<2'!-1m 7m %#,A+'!-1m .0m #*m +#*A,m 1#m &m ',!0#+#,2"-mm*-m*0%-m"#m*-1mB*2'+-1m@-1m#m',!*31-m*m1#!3#,!'m"#*m%#,-+m#129m "'1.-,' *#Ym ',m #+ 0%-Zm *1m &#00+'#,21m %#,A+'!1m .0m "#2#0+',0m *m $3,!'-,*'""m "#m *-1m %#,#1m #,m #12m #1.#!'#m 1-,m 2-"4>m *'+'2"1Ym *m m ^0%#2',%m ,"3!#"m -!*m #1'-,1m m #,-+#1_m #1m 3,m +<2-"-m "#m %#,<2'!m ',4#01m +#"',2#m #*m !3*m 1#m .3#"#,m !0#0m #m '"#,2'$'!0m ,3#41m +32!'-,#1m #,m %#,#1m !,"'"2-1m 7m - 1#040m 13m #$#!2-m $#,-2>.'!-Ym "#+91Zm 2+ '<,m 1#m .3#"#,m "#2#!20m $#,-2'.-1m "#m ',2#0<1m .0m .-12#0'-0+#,2#m '"#,2'$'!0m *m +32!'A,m 0#1.-,1 *#m "#m *-1m +'1+-1Ym ,m #12#m 20 (-m 1#m &m "#100-**"-m 3,m .- *!'A,m "#m m #,m //'#-O '&)m m .02'0m "#m *m *>,#m "- *#m &.*-'"#m "#*m 2'.-m b'#*m "#m .-cm LHjGGIYm .*'!,"-m ','!'*+#,2#m#*m+329%#,-m/3>+'!-mm^2'*m#2,-m3*$-,2-_m1- 0#mGMYFFFm1#+'**1m 1#m &m "#100-**"-m 3,m !-*#!!'A,m "#m +32,2#1m !-+.3#12m .-0m IYHLNm $+'*'1m HYm m .02'0m "#m JFFm $+>*'1m Hm 1#m - 1#040-,m "'4#01-1m $#,-2'.-1m +32,2#1m #,m *1m "'$#0#,2#1m #2.1m "#m !0#!'+'#,2-m "#m *m .*,2Ym *%3,-1m "#m #12-1m +32,2#1m 1#m &,m "#1!0'2-m !-,m "#2**#m %#,#0,"-m 3,m !29*-%-m "#m *-1m $#,-2'.-1m - 1#04"-1m #,m !"m $+'*'Zm*%3,-1m"#m*-1m!3*#1m.3#"#,m2#,#0m',2#0<1m!-+#0!'*Ymm 0m +#"'0m *m 21m "#m +32!'A,m "#m *m .- *!'A,m 1#m &,m ,*'8"-m !320-m %#,#1Zm *m $'2-#,-m"#12301mZm*-1m$!2-0#1m"#m','!'!'A,m"#m*m20"3!!'A,m>m3OI#-)J>O 7m#*m0#!#.2-0m"#m#2'*#,-m;Ym-1m+32,2#1m"#2#!2"-1m&,m.#0+'2'"-m!*!3*0m*m21m "#m +32!'A,m "#m *m .- *!'A,Zm 3,m +32!'A,m !"m GZKm Ym ,m #*m !1-m "#m m 1#m &m .-"'"-m- 2#,#0m3,m+32,2#m!-,m$#,-2'.-m* ',-Zm"#+-120,"-m1>m*m#$#!2'4'""m"#*m +<2-"-mm#,m+#*A,Ym"#+91Zm.0*#*+#,2#m1#m,*'80-,m*-1m+'1+-1m%#,#1m #,m-20m.- *!'A,m+32%#,'8"m',"#.#,"'#,2#Ym m+ '<,m 1#m 0#*'8Am 3,m #123"'-m "#m !-m !-,m GGIm !!#1'-,#1m "#m +#*A,7m 1#m '"#,2'$'!0-,m GOm &.*-2'.-1m "'12',2-1m #,m #*m %#,m>Zm 3,-m "#m #**-1Zm !-,m 3,m m /3#m .0-4-!m3,m!+ '-m"#m+',-9!'"-m7m/3#m1A*-m1#m#,!3#,20m#,m*m!!#1'A,mmKFKLFHm7m "-1m &.*-2'.-1m #,m #*m %#,m ;Zm 3,-m "#m *-1m !3*#1m 2+ '<,m !-,2'#,#m 3,m m /3#m .0-4-!m3,m!+ '-m"#m+',-9!'"-Ymm I *m m $!'*'209m *-1m #123"'-1m "#m %#,<2'!m ',4#01m #,m +#*A,m 7m 0#m *m .3#02m m $3230-1m #123"'-1m "#m %#,A+'!m $3,!'-,*m #,m 3,m %#,-+m 0#!'#,2#+#,2#m 1#!3#,!'"-Ym 12#m20 (-m&m0#.0#1#,2"-m2+ '<,m#*m.0'+#0m.1-m.0m.-"#0m"#100-**0m,3#41m .- *!'-,#1m"#mm#,m+#*A,m!-,m+7-0#1m211m"#m+32!'A,m7m#,m-20-1m$-,"-1m %#,<2'!-1Ym T Jm &O'&9(O3O&O!(9'#O&O'&9(O (.,)/#9(O T T BMTT T BMBTTT T BMBMBTT m #1.#!'#m //'#-O '&)m Em .#02#,#!#m m *m $+'*'m "#m *1m 3!30 '29!#1Zm m *m 20' 3m #*-2&0'##Zm 13 20' 3m 3!3+#0',#Zm %<,#0-m //'#-Ym m .02#m "#m #12#m %<,#0-m /3#m ',!*37#m 2+ '<,m #*m .#.',-m ^//'#-O -.#0/-JO ^ #$$0#7Zm GOOF_Zm #,!-,20+-1m -20-1m "-1m %<,#0-1m /3#m %03.,m #1.#!'#1m "#m '+.-02,!'m #!-,A+'!m m ,'4#*m +3,"'*m !-+-m #.,/&&/-O &(./-m ^1,">_m 7m //,#.O **)m ^!* 8m 7m !* !>,_m ^ #$$0#7Zm GOOF_Ym *m %<,#0-m //'#-O 1#m "'4'"#m #,m "-1m 13 %<,#0-1m /3#m 1#.0,m 91'!+#,2#m *1m #1.#!'#1m $0'!,1m "#m *1m 1'92'!1Ym *m .0'+#0m 13 %<,#0-Zm "#,-+',"-m &)Zm ',!*37#Zm #,20#m -20-1Zm *m +#*A,Ym *m 1#%3,"-m 13 %<,#0-Zm //'#-Zm ',!*37#Zm #,20#m -20-1Zm *m .#.',-m ^ #$$0#7Zm GOOF_Ym 6'12#,m "'12',21m !*1'$'!!'-,#1m "#*m +#*A,Zm 1',m #+ 0%-Zm 3,m "#m *1m +91m !-+.*#21m #1m *m .0-.3#12m .-0m '202m 7m !-* -0"-0#1m ^HFFF_m /3#m "'4'"#m *m #1.#!'#m#,mGLm%03.-1ZmKm"#m*-1m!3*#1m1#m%03.,m#,m*m13 #1.#!'#O!,-.#-m7mGGm#,m*m 13 #1.#!'#m'&)Ym *m+#*A,m#1m3,m#1.#!'#m!-,m3,m%0,m40' '*'""m%#,<2'!m7m#62#,1+#,2#m!3*2'4"m #,m2-"-m#*m+3,"-Ym,m0#!'#,2#m#123"'-m"#m1#!3#,!'1m"#mm,3!*#0m7m.*1+>"'!1m #,m GFFm !!#1'-,#1m "#m //'#-m "#m "'12',21m 8-,1m %#-%09$'!1m ^$0'!Zm 3120*'m 7m 1'_m &m 13%#0'"-m /3#m #*m +#*A,m 2'#,#m 3,m -0'%#,m 1'92'!-m 7m /3#m .0- *#+#,2#m 13m ,2#!#1-0m1'*4#120#m1#m-0'%',Am#,m*m,"'m^# 12',ZmHFGF_Ymm T BMBMCTT m .*,2m "#*m +#*A,m #1m ,3*m 7m &#0 9!#m 7m .3#"#m 1#0m "#m .-02#m 0120#0-m -m 20#."-0m "#.#,"'#,"-m "#m *1m !-,"'!'-,#1m "#m !3*2'4-m m *1m !3*#1m 1#m 1-+#2Ym 3m 1'12#+m 0"'!3*0m #1m 3,",2#Zm +37m 0+'$'!"-m 7m "#m 09.'"-m "#100-**-Ym -1m 2**-1m .0',!'.*#1m#129,m0#!3 '#02-1m"#m$-0+!'-,#1m.'*-11m7m.0#1#,2,m,3"-1m#,m*-1m/3#m1#m "#100-**,m &-(1Zm 80!'**-1m 7m $*-0#1Ym -1m ,3#4-1m 2**-1m 0-2,m "#m *1m 6'*1m "#m *1m &-(1Ym m &-(m 2'#,#m $-0+m "#m *'+ -m -4"-Zm & '23*+#,2#m .#,2%-,*m 7m !-,m *-1m +90%#,#1m "#,2"-1Ym 1m &-(1m 2+ '<,m 1-,m 4#**-11m .-0m #*m #,4<1Ym 1m $*-0#1m 1-,m "#m !-*-0m+0'**-m7m.3#"#,m1#0m+1!3*',1Zm$#+#,',1m-m&#0+$0-"'21Ym1m.0'+#01m#,m K (.,)/#9( El melón y la genómica de melón "#100-**01#m1-,m*1m$*-0#1m+1!3*',1m#,m*-1m#,20#,3"-1m.0'+0'-1m+'#,201m/3#m*1m $#+#,',1m7m&#0+$0-"'21m.0#!#,m+91m20"#m#,m*1m0+'$'!!'-,#1m.-12#0'-0#1Ymm .-*','8!'A,m #1m #,2-+A$'*_m 7m +7-0'20'+#,2#m 0#*'8"m .-0m #(1m ^,"#*Zm GONH\m -,$-02#m7m!-*YZmHFFJ_Ym m $-0+m "#*m $032-m #1m +37m 40' *#m ^#1$<0'!Zm #*>.2'!m 3m -4"_Ym #m &,m .-"'"-m '"#,2'$'!0m %#,#1m /3#m .0#!#,m #120m 0#*!'-,"-1m !-,m *m $-0+m "#m $032-m .-0m 13m '+.*'!!'A,m#,m*m"#2#0+',!'A,m"#m*m$-0+m"#m*m$*-0m-m"#*m-40'-Zm#,20#m#**-1Zm#*m%#,m m^+-,-'!-_m7m#*m%#,m*m^.#,29+#0-_m^#0',m7m!-*ZmHFFH_Ym 0m *m !-02#8m "#*m $032-m #6'12#m 2+ '<,m 3,m %0,m 40' '*'""m 2,2-m "#m !-*-0#1m ^4#0"#Zm +0'**-Zm ,0,("-m -m *,!-_m !-+-m "#m 2#62301Ym ,!-,20+-1m .'#*#1m *'11Zm 0#2'!3*"1m-m#120'"1Ymm.3*.m.3#"#m1#0m *,!Zm+0'**Zm,0,("m-m4#0"-1Ym*m $032-m "#*m +#*A,m .3#"#m +"300m "#m +,#0m !*'+2<0'!m -m ,-m !*'+2<0'!m 1#%B,m *m 40'#""m +"30!'A,m !*'+2<0'!m 1#m !0!2#0'8m .-0m 3,m 3+#,2-m "#m *m 21m "#m 0#1.'0!'A,m7m#1m','!'"m.-0m3,m.'!-m#,m*m!-,!#,20!'A,m"#m#2'*#,-Ym',m#+ 0%-Zm*m +"30!'A,m,-m!*'+2<0'!m1#m!0!2#0'8m.-0m3,m"'1+',3!'A,m!-,2',3m#,m*m21m"#m 0#1.'0!'A,m 7m #,m *m .0-"3!!'A,m "#m #2'*#,-m ^--0#m 7m !-*Zm HFFH_Ym m '"#,2'$'!!'A,m "#m *%3,-1m /(.#..#0O ,#.O )/-O ^1_m 0#1.-,1 *#1m "#m #12#m !09!2#0m (3,2-m !-,m *m *-!*'8!'A,m "#m %#,#1m !,"'"2-1m "#m $'0+#8m "#*m $032-m #,m *>,#1m "#m ',20-%0#1'A,m ^1_m - 2#,'"1m "#m *-1m .0#,2*#1m m GLGIMKm 7m GGGZm #,20#m -20-1m #123"'-1Zm &,m .#0+'2'"-m !-+#,80m m !-+.0#,"#0m !A+-m $3,!'-,m #12#m +#!,'1+-m ^-0#,-m 7m !-*YZm HFFN_Ym121m!0!2#0>12'!1m&,m&#!&-m/3#m#*m+#*A,m1#m!-,1'"#0"-m!-+-m3,m"#m*1m #1.#!'#1m +-"#*-m .0m .-"#0m !-+.0#,"#0m #*m .0-!#1-m "#m +"30!'A,m "#*m $032-m 1>m !-+-m13m0#%3*!'A,mm,'4#*m%#,<2'!-m7m+-*#!3*0Ym T BMBMDTTTTT *m +#*A,m 1#m!3*2'4m #,m 8-,1m 20-.'!*#1m 7m 13 20-.'!*#1m 1#!1Ym,m 30-.Zm 1#m !3*2'4m #12!'-,*+#,2#m#,m4#0,-m7m.0'+4#0Ym#%B,m*-1mB*2'+-1m"2-1m"#m*mZm#,mHFGGm &',m #0m #*m .0'+#0m .0-"3!2-0m +3,"'*m !-,m GIYFNKYKFFm 2-,#*"1Zm 1#%3'"-m .-0m 09,m !-,m GYNFGYNIFm 7m .-0m 30/3>m !-,m GYLJMYOOFZm +'#,201m /3#m 1.@m /3#"m #,m 1<.2'+-m *3%0m!-,m3,m.0-"3!!'A,m"#mNLOYJMKm2-,#*"1m^'%30mGYG_Ym Lm &O'&9(O3O&O!(9'#O&O'&9(O (.,)/#9(O m m (&30 TBMBOT09$'!-m!-,m*-1m.0',!'.*#1m.0-"3!2-0#1m"#m+#*A,mm,'4#*m+3,"'*Ym1.@m1#m#,!3#,20m#,m#*m 1<.2'+-m*3%0m^,2mGFFFW[m.0#!'-m+#"'-m"#m2-"1m*1m+-,#"1m',2#0,!'-,*#1m2-+,"-m#*m"A*0m+#0'!,-m !-+-m0#$#0#,!'\m[m-,#*"m+#20'!_Ym3#,2#mZm&22.[ii$-122Y$-Y-0%i1'2#iIJHi"#$3*2Y1.6m^HFGI_Ym m m 'm ,*'8+-1m *1m #6.-02!'-,#1Zm 1.@m #1m #*m .0'+#0m #6.-02"-0m +3,"'*m !-,m IMLYGFIm 2-,#*"1Zm 1#%3'"-m "#m 32#+*m 7m -,"301m ^'%30m GYH_Ym 12#m "2-m !-00- -0m #*m &#!&-m "#m /3#m #,m 1.@m #*m +#*A,m #1m 3,m .0-"3!2-m ,-m 1A*-m +37m "#+,""-m .-0m .02#m "#*m !-,13+'"-0Zm 1'm ,-m /3#m "#+91Zm 2'#,#m +3!&m "#+,"m m ,'4#*m ',2#0,!'-,*Zm 7m .-0m *-m 2,2-Zm 3,m '+.-02,2#m ..#*m #,m *m #!-,-+>m "#*m .>1Ym #m "#!'0m /3#m #,m 1.@m #*m +#*A,m #1m *m 1#%3,"m #1.#!'#m &-02>!-*m +91m !3*2'4"m "#1.3<1m "#*m 2-+2#Ym ,m #*m HFGGm 1#m !3*2'40-,m IHYFFFm m 7m 1#m .0-"3(#0-,m NLOYJMKm 2-,#*"1m"#m+#*A,Ymm+7-0m.02#m"#m*m13.#0$'!'#m!3*2'4"m"#m+#*A,m1#m#,!3#,20m #,m*1m0#%'-,#1m"#m30!'Zm12'**m*m,!&m7m,"*3!>m^&22.[ii$-122Y$-Y-0%_Ym M (.,)/#9( El melón y la genómica de melón m m (&30 TBMCOT09$'!-m"#m*-1m.>1#1m!-,m+91m#6.-02!'A,m"#m+#*A,mm,'4#*m+3,"'*Ym1.@m1#m#,!3#,20m#,m .0'+#0m*3%0Ymm3#,2#mZm&22.[ii$-122Y$-Y-0%i1'2#iIJHi"#$3*2Y1.6m^HFGI_Ym m BMBMET TTTT m'+.-02,!'m#!-,A+'!m"#*m+#*A,m#,m,3#120-m.>1m(312'$'!m/3#m#6'12,m#+.0#11m .0-"3!2-01m "#m 1#+'**1m ',2#0#1"1m #,m +#(-00m #12m #1.#!'#m 7m ".20*m m *1m ,#!#1'""#1m"#m*-1m.0-"3!2-0#1m7m*-1m!-,13+'"-0#1Ym*%3,-1m"#m*-1m- (#2'4-1m"#m#12m +#(-0m %#,<2'!m 1-,m - 2#,#0m .0-"3!!'-,#1m !-,m 3,m *2-m 0#,"'+'#,2-Zm ',!-0.-00m 0#1'12#,!'1m m .*%1m -m #,$#0+#""#1m 7m *m +#(-0m "#*m $032-m 2,2-m #,m !0!2#0#1m +-0$-*A%'!-1m ^.-0m #(#+.*-m *m $-0+m "#*m $032-_m !-+-m -0%,-*<.2'!-1m ^.-0m #(#+.*-m #*m 0-+m -m *m "3*830_Ym 1m 0#1'12#,!'1m 31!"1m 1-,m .0',!'.*+#,2#m $0#,2#m m 4'031m !-+-m.-0m#(#+.*-Zm#*m4'031m"#*m+-1'!-m"#*m.#.',-Zm//',O)-#O#,/-m^_m-m #*m 4'031m "#m *1m +,!&1m ,#!0A2'!1m #*m +#*A,Zm &)(O ,).#O *).O #,/-m ^_m 7m $0#,2#m m &-,%-1m !-+-m #*m ->"'-m ^))-*",O 2(."##FO)&)0#()'3-O #"),,/'_m -m m 310'3+m ^/-,#/'O )23-*),/'O $Ym 1.Ym '&)(#-_Ym 1'+'1+-Zm 1#m .0-!30m -.2'+'80m *m .0-"3!!'A,m !-,m 40'#""#1m /3#m -$0#8!,m 3,m *2-m 0#,"'+'#,2-m #,m !-,"'!'-,#1m "4#011m "#m 1#/3>m 7m #*#4"m 1*','""m -m /3#m .#0+'2,m 3,m "#!3"m !*'""m #,m .-12!-1#!&Y ,2#1m "#*m "#1!3 0'+'#,2-m "#m *-1m +0!"-0#1m +-*#!3*0#1m #12#m 2'.-m "#m +#(-0m "#.#,">m "'0#!2+#,2#m "#m *m #4*3!'A,m +#"',2#m *m - 1#04!'A,m "'0#!2m "#*m $#,-2'.-Ym ',m #+ 0%-Zm *m #6.0#1'A,m $#,-2>.'!m #1m .0-"3!2-m "#m *m ',2#0!!'A,m "#*m Nm &O'&9(O3O&O!(9'#O&O'&9(O (.,)/#9(O %#,-2'.-m !-,m #*m + '#,2#m 7m ,-m 2-"-1m *-1m $!2-0#1m + '#,2*#1m .3#"#,m 1#0m !-,20-*"-1Zm&#!&-m/3#m"'$'!3*2m#*m.0-!#1-m"#m1#*#!!'A,m^**0"ZmGOOO_Ym 0!'1m m *1m ,3#41m 2#!,-*-%>1m #,m '-*-%>m +-*#!3*0m 1#m &,m "#100-**"-m &#00+'#,21m !-+-m *-1m +0!"-0#1m +-*#!3*0#1m /3#m .#0+'2#,m *m 1#*#!!'A,m 1'12'"Ym ,m*>,#1m%#,#0*#1Zm*-1m+0!"-0#1m%#,<2'!-1m.#0+'2#,m0120#0m!-,m0.'"#8m#*mm "#m*m.*,2m/3#m1#m#129m1#*#!!'-,,"-m.#0+'2'<,"-,-1m1 #0m1'm#*m*#*-m"#m3,m%#,m1#m #,!3#,20m-m,-m#,m*m.*,2Ymm -1m +0!"-0#1m %#,<2'!-1m 1-,m .-*'+-0$'1+-1m &#0#" *#1m "#m $-0+m +#,"#*',m 1#,!'**m^20!&,m7m#"ZmGOOO_Ym3m40' '*'""m.3#"#m1#0m"#2#!2"m7m32'*'8"m#,m#*m #123"'-m "#m "'4#01-1m !0!2#0#1m %#,<2'!-1Ym ,m *m +#(-0m !*91'!m 1#m 32'*'8 ,m *-1m +0!"-0#1m +-0$-*A%'!-1m /3#m ,-0+*+#,2#m 1#m .0-"3!>,m m .02'0m "#m 3,m +32!'A,m "#m3,m%#,m","-m!-+-m0#13*2"-m#*m$#,-2'.-m"'$#0#,!'"-Ym-12#0'-0+#,2#m1#m310-,m *-1m +0!"-0#1m 1"-1m #,m '1-#,8'+1m -m 40',2#1m +-*#!3*0#1m "#m 3,m +'1+m .0-2#>,m ^2# ',1m 7m --"7Zm GONO\m !'**',m 7m !,"*'-1Zm GONI_Ym "-m /3#m !"m '1-#,8'+m2'#,#m3,m"'12',2m!-+.-1'!'A,m#,m+',-9!'"-1m2+ '<,m0#13*2m"'12',2m13m !0%m #*<!20'!Ym 12m !0!2#0>12'!m 1#m 31 m .0m 1#.00*1m +#"',2#m #*#!20-$-0#1'1m 4'13*'8,"-m #*m .20A,m "'$#0#,!'*m "#m !"m ',"'4'"3-Ym -12#0'-0+#,2#Zm 1#m "#100-**0-,m *-1m +0!"-0#1m +-*#!3*0#1m 1"-1m #,m *-1m .-*'+-0$'1+-1m "#m Ym -1m-.,#.#)(O,!'(.O(!".O)&3'),*"#-'O^1_m1-,m+0!"-0#1m 1"-1m#,m*1m "'$#0#,!'1m"#m*-,%'23"m"#m$0%+#,2-1m"#mm- 2#,'"-1mm.02'0m"#m*m"'%#12'A,m"#*m %#,-+Ym-1m$0%+#,2-1m1#m"'%'#0#,m!-,m"'12',21m#,8'+1m"#m0#120'!!'A,m/3#m!-02,m #*mm.-0m*3%0#1m#1.#!>$'!-1m"#m*m1#!3#,!'m^"',1m"#m0#120'!!'A,_Ymm.0#1#,!'m "#m.-*'+-0$'1+-1m.3#"#m$#!20mm*1m"',1m"#m0#120'!!'A,m'+.'"'#,"-m/3#m*m#,8'+m "'%'#0m !-00#!2+#,2#m 7m .-0m *-m 2,2-m /3#m !"m %#,-2'.-m +3#120#m 3,m .20A,m "'$#0#,!'*m^3"0!!-j0,1ZmGOOL\m*'4#0ZmHFFG_Ymm 1'+'1+-Zm *-1m +0!"-0#1m 1"-1m #,m *m 2<!,'!m "#m *m #!!'A,m #,m "#,m "#m *m -*'+#01m ^_m &,m 1#04'"-Zm #,20#m -201m 32'*'""#1Zm .0m 1#%3'0m !-,12037#,"-m 7m 1230,"-m *-1m +.1m %#,<2'!-1Ym 7m +3!&-1m 2'.-1m "#m +0!"-0#1m "#0'4"-1m "#m *m 2<!,'!m "#m *m Zm !-+-m *-1m '*&# #O ,!'(.O (!".O )&3'),*"#-'O ^1_Zm *-1m ()'O '*&# #O )&3'),*"#O m ^1_Zm *-1m +'!0-12<*'2#1m -m #'*&O +/(O *.-m^1_m-m*-1m1m^#(!&O/&).#O)&3'),*"#-'JEO-1m1m1#m 1,m#,m*m "'%#12'A,m !-,m #,8'+1m "#m 0#120'!!'A,m "#*m m %#,A+'!-m 7m .-12#0'-0+#,2#m 13m +.*'$'!!'A,m +#"',2#m m ^-1m 7m !-*YZm GOOK_Ym -1m 1m 1#m %#,#0,m .-0m *m +.*'$'!!'A,m*#2-0'm"#m1#%+#,2-1m"#mm%#,A+'!-mm.02'0m"#m3,m1-*-m!# "-0m "#m 1#!3#,!'m !-02m 7m 0 '200'm ^'**'+1Zm GOOF_Ym -1m 1m 1-,m $0%+#,2-1m "#m 1#!3#,!'1m "-,"#m &7m 3,m 0#.#2'!'A,m #,m 29,"#+m "#m HjLm ,3!*#A2'"-1Zm 3,/3#m #12m O (.,)/#9( El melón y la genómica de melón *-,%'23"m.3#"#m40'0m#,m$3,!'A,m"#m*m40'#""Ym0!'1mm#12m40'!'A,m1#m.3#"#,m "#100-**0m +0!"-0#1m 1"-1m #,m *m "#2#!!'A,m "#*m ,B+#0-m "#m 0#.#2'!'-,#1m .0#1#,2#1m#,m*-1m%#,-2'.-1m,*'8"-1m^+"m7m!-*YZmGONH\m-,8*-m7m!-*YZmHFFK_Ym m.#10m"#m#6'12'0m3,m%0,m40'#""m"#m+0!"-0#1m+-*#!3*0#1Zm#,m*-1mB*2'+-1m@-1m 1#m &m &#!&-m 3,m 31-m +91m #6&312'4-m "#m *-1m +0!"-0#1m 1Ym 12#m 2'.-m "#m .-*'+-0$'1+-m #1m +37m 3,",2#m #,m #*m m ^0--)#1Zm GOOO_m 7m #6'12#,m 40'1m 2#!,-*-%>1m 09.'"1m 7m #$'!'#,2#1m /3#m .#0+'2#,m 13m "#1!3 0'+'#,2-m 7m 13m %#,-2'."-m ^+'2&m 7m !-*YZm HFGH_Ym *%3,-1m #(#+.*-1m "#m 2<!,'!1m .0m 13m "#1!3 0'+'#,2-m 1-,m *m &' 0'"!'A,m+#"',2#m+'!0-+20'!#1m^-0#4'28m7m!-*YZmHFFI_Zm#*m,9*'1'1m#(O-#&#)mm.02'0m "#m 1#!3#,!'1m "#m 1m ^2*,--O +/(O !_m ^#&'1m 7m !-*YZm HFGH_m -m *m 0#1#!3#,!'!'A,m "#m +.*'!-,#1m ^&-'m 7m !-*YZm HFFM_Ym !23*+#,2#Zm #,m #1.#!'#1m !-,m #*m %#,-+m 1#!3#,!'"-m 1#m .3#"#,m - 2#,#0m !'#,2-1m "#m +'*#1m "#m 1m m .02'0m "#m 0#1#!3#,!'!'A,m "#m 40'#""#1Ym 0m 13m %#,-2'."-m 1#m &,m "#100-**"-m 2<!,'!1m !-+-m#*m31-m"#m1-,"1m/,Zm#,20#m+3!&1m-201Ym#!'#,2#+#,2#m1#m&m1230"-m#*m +.m %#,<2'!-m "#m +#*A,m 201m #*m "#100-**-m "#m +0!"-0#1m +-*#!3*0#1m 2'.-m 1m ^0!'j1m7m!-*YZmHFGH_Ym m BMBMFTTTTTT BMBMFMBTTTTT ,m#*mHFFKm1#m0#*'8Am*m.0'+#0m0#3,'A,m',2#0,!'-,*m"#m%#,A+'!m"#m3!30 '29!#1m #,m0!#*-,Zm"-,"#m1#m#12 *#!'Am#*m(.,(.#)(&O//,#.O()'#-O(#.#.#0m^3_Zm /3#m 2-+Am "#!'1'-,#1m "#m !'#02m 0#*#4,!'m .0m *m ',4#12'%!'A,m #,m #12m #1.#!'#Ym ,m "#m #**1m $3#m - 2#,#0m 3,m #6&312'4m !-*#!!'A,m "#m 1#!3#,!'1m "#m 1Ym 20m "#!'1'A,m 0#*#4,2#m$3#m3,'$'!0m*-1m+.1m%#,<2'!-1m/3#m&12m#,2-,!#1m1#m& >,m"#100-**"-m "#m3,m+-"-m',"#.#,"'#,2#m#,m"'12',2-1m* -02-0'-1Ym#m#12#m+-"-m1#m- 2#,"0>m3,m +.m %#,<2'!-m !-,1#,1-m +3!&-m +91m 1230"-m ^'8m 7m !-*YZm HFGG_Ym ',*+#,2#Zm 1#m "#!'"'Am#* -00m3,mB,'!m.9%',m5# m"-,"#m2-"-1m*-1m"2-1m%#,<2'!-1m7m%#,A+'!-1m $3#0,m"#m!!#1-m.B *'!-m^&22.[ii555Y'!3%'Y-0%_Ym m _mmmm ,m +.m %#,<2'!-m -m +.m "#m *'%+'#,2-m #1m 3,m +.m "#m +0!"-0#1m .-*'+A0$'!-1m "-,"#m1#m"#$',#,m*1m"'12,!'1m#,20#m*-1m+0!"-0#1m#,m$3,!'A,m"#m*m$0#!3#,!'m"#m 0#!-+ ',!'A,m /3#m &m & '"-m #,20#m #**-1Ym #.0-"3!#,m *m #1203!230m "#m *-1m !0-+-1-+1m+-120,"-m*1m.-1'!'-,#1m"#m*-1m%#,#1m^#,m!1-m"#m/3#m#*m+0!"-0m#12<m GF &O'&9(O3O&O!(9'#O&O'&9(O (.,)/#9(O ,!*"-m#,m3,m%#,_m-m"#m+0!"-0#1m,A,'+-1m 1"-1m#,m$0%+#,2-1m"#m1#!3#,!'1m ,-m!-"'$'!,2#1Ymm ,m +.m %#,<2'!-m 1#m - 2'#,#m %#,#0*+#,2#m m .02'0m "#m .- *!'-,#1m 1#%0#%,2#1m - 2#,'"1m "#m !038+'#,2-1m #,20#m "-1m *>,#1m .0#,2*#1Ym 3,2-m +91m *#("-1m $'*-%#,<2'!+#,2#m1#,m*-1m.0#,2*#1Zm+91m',$-0+2'4-m.-"09m1#0m#*m!038+'#,2-Zm7m /3#m #*m %0"-m "#m .-*'+-0$'1+-m 1#09m +91m #*#4"-Ym 6'12#,m "'12',2-1m +.1m %#,<2'!-1m "#m +#*A,m ^3"0!!-j0,1Zm GOOL\m <0',m 7m !-*YZm HFFH_Ym #0-m !"m +.m %#,<2'!-m &m 1'"-m #* -0"-m !-,m "'12',21m *>,#1m .0#,2*#1m -m "'12',2-1m 2'.-1m "#m .- *!'-,#1Ym -1m 2'.-1m "#m +0!"-0#1m /3#m 1#m &,m .-1'!'-,"-m #,m !"m +.m %#,<2'!-m 2+ '<,m 1-,m "'12',2-1Ym*'4#0m7m!-*Ym^HFFG_m#* -00-,m3,m+.m%#,<2'!-mm.02'0m"#m3,m.- *!'A,m Hm- 2#,'"m"#*m!038+'#,2-m#,20#m"-1m*>,#1m.0#,2*#1Zm3,m#*m2'.-m()),/-mb'#*m"#m 1.-cmGGGm7m*m!!#1'A,m!-0#,m-,%5&,m&0+'ZmmGLGIMKYm12#m+.m1#m%#,#0Am ','!'*+#,2#m !-,m JGGm +0!"-0#1m 1Ym -12#0'-0+#,2#m -,8*-m 7m !-*Ym ^HFFK_m %#,#00-,m 3,m .- *!'A,m "#m *>,#1m "- *#m &.*-'"#1m ^1_Zm m .02'0m "#*m +'1+-m !038+'#,2-m ,2#0'-0Ym m 4#,2(m "#m *1m 1m #1m /3#m !-,12'237#,m 3,m .- *!'A,m ',+-02*m 7m /3#m 1-,m 2-2*+#,2#m &-+-!'%A2'!1m 7m .-0m *-m 2,2-Zm #,m *1m %#,#0!'-,#1m .-12#0'-0#1m - 2#,'"1m .-0m 32-$#!3,"!'A,Zm 1#m - 2'#,#,m .*,21m '"<,2'!1m m *1m .0#,2*#1m ^-,8*-m 7m !-*YZm HFFK_Ym m .02'0m "#m #12m .- *!'A,m 1#m %#,#0Am 3,m ,3#4-m +.m %#,<2'!-m 1"-m #,m #*m ,2#0'-0Zm 7m $',*+#,2#m 1#m $31'-,Am *m ',$-0+!'A,m "#m + -1m +.1Ym *m 0#13*2,2#m !-,2#,>m .0-6'+"+#,2#m JMOm +0!"-0#1m !-,m 3,m "#,1'""m "#m HYKm !i+0!"-0m ^-,8*-m 7m !-*YZm HFFK_Zm *m !3*m 1#m @"'#0-,m ,3#4-1m +0!"-0#1m2'.-m1m7m1m#,m.-12#0'-0#1m20 (-1m^#*#3m7m!-*YmHFFOZm#0,9,"#8j '*4m 7m !-*YZm HFFN_Ym 30,2#m #*m HFGGm 7m "#,20-m "#*m 3m 1#m .3 *'!Am 3,m ,3#4-m +.m !-,1#,1-m 1"-m #,m *m $31'A,m "#m *m ',$-0+!'A,m /3#m & >,m .-02"-m -!&-m +.1m %#,<2'!-1m .3 *'!"-1m ,2#0'-0+#,2#Ym 12#m ,3#4-m +.m !-,1#,1-m !-,2'#,#m GKOHm +0!"-0#1m ^LJFm 1Zm IIFm 1Zm HKHm 1Zm HIOm 1Zm NOm 1m 7m GGm !0!2#0#1m +-0$-*A%'!-1Zm#,20#m-20-1_m!-,m3,m"#,1'""m+#"'m"#mFZMHm!+i+0!"-0m^'8m7m!-*YZm HFGG_Ym,m#12#m+.m!-,1#,1-m2+ '<,m1#m&,m.-1'!'-,"-m2-"-1m*-1m1m"#1!0'2-1m #,m+#*A,m&12m*m$#!&YYm m _mmm 20m &#00+'#,2m $0#!3#,2#+#,2#m 31"m #,m '-2#!,-*-%>m #1m *m 20,1$-0+!'A,m %#,<2'!m.0m*m- 2#,!'A,m"#m.*,21m20,1%<,'!1Ym,m#*m!1-m"#*m+#*A,Zm3,/3#m1#m &m !-,1#%3'"-m *m 20,1$-0+!'A,m !-,m !,).,#/'O ./' #(-FO #1m 3,m +<2-"-m ',#$'!'#,2#Ym m 20,1$-0+!'A,m #,m +#*A,m 1#m 32'*'8Am .-0m .0'+#0m 4#8m !-,m <6'2-m .-0m ,%m 7m 03+#2m #,m GOOFm .#0-m *m 21m "#m #$'!'#,!'m $3#m +37m (Ym ,-m "#m *-1m GG (.,)/#9( El melón y la genómica de melón ',!-,4#,'#,2#1m #,m *m 20,1$-0+!'A,m "#m *1m .*,21m "#m +#*A,m $3#m #*m "#1!3 0'+'#,2-m "#m /3#m !'#02-1m #6.*,2#1m .0-"3!>,m ,'4#*#1m +91m *2-1m "#m #2'*#,-m "30,2#m *m ',-!3*!'A,m!-,m!,).,#/'O^830m7m!-*YZmHFFF_Ym12m.0-"3!!'A,m"#m#2'*#,-m',&' >m *m#6.0#1'A,m"#*m%#,m0#,m7m!-,1#!3#,2#+#,2#m*m20,1$-0+!'A,m^-,)m7m!-*YmHFFN_Ym !23*+#,2#m2-"4>m1#m#129,m'"#,2'$'!"-m*-1m$!2-0#1m.-0m*-1m!3*#1m*m#$'!'#,!'m"#m 20,1$-0+!'A,m#,m+#*A,m#1m (m^&-4#*-,m7m!-*YZmHFGG_Ymm _mm 0m .-"#0m 0#*'80m #6.#0'+#,2-1m !-+-m #*m !*-,(#m .-1'!'-,*m "#m %#,#1m 7m .0- 0m *m $3,!'-,*'""m "#m !'#02-1m %#,#1Zm &m 1'"-m ',"'1.#,1 *#m "'1.-,#0m "#m !-*#!!'-,#1m "#m 1m ^0-+-1-+1m 02'$'!'*#1m !2#0',-1_Ym -1m 1m 1-,m 2+ '<,m "#m %0,m 32'*'""m.0m.-"#0m"#100-**0m+.1m$>1'!-1Zm-m&!#0m#123"'-1m"#m+'!0-1',2#,'m!-,m -201m #1.#!'#1Zm #,20#m -201m .*'!!'-,#1m ^3"'+,m 7m !-*YZm HFFF\m #*#3m 7m !-*YZm HFFM\m -,89*#8m 7m !-*YZm HFGF_Ym 1m .0'+#01m %#,-2#!1m "#m 1m #,m +#*A,m $3#0-,m !-,1203'"1m m .02'0m "#m *m *>,#m jGm ^3-m 7m !-*YZm HFFG_Ym -12#0'-0+#,2#m 1#m &,m %#,#0"-m -201m %#,-2#!1m /3#m 1#m &,m 31"-m .0m "#2#!20m %#,#1m "#m ',2#0<1m /3#m !-,$'#0#,m0#1'12#,!'1mm.2A%#,-1m^'#2-m7m!-*YZmHFFL_m-m%#,#1m/3#m"#2#0+',,m#*m1#6-m #,m *1m $*-0#1m "#m *1m .*,21m "#m +#*A,m ^-3*#+m 7m !-*YZm HFFN_Ym "#+91Zm *-1m 1m .#0+'2#,m *-!*'80m +0!"-0#1m +-*#!3*0#1m "#m 3,m +.m %#,<2'!-m 7m "#m #12#m +-"-m 0#*'80m+.1m$>1'!-1m"#m*m#1.#!'#Zm.0-.-0!'-,,"-m,!*(#1m.0m*m*-!*'8!'A,m"#m %#,#1m !,"'"2-1m 7m .0m #*m #,1+ *(#m "#m %#,-+1m ^-,89*#8m 7m !-*YZm HFGF _Ym #"',2#m!*-,(#m.-1'!'-,*m1#m&,m'1*"-m*-1m%#,#1m"#m0#1'12#,!'m.FO(-0m7m)'N<m $0#,2#mm*%3,1mm#,$#0+#""#1m/3#m13$0#m#*m!3*2'4-m"#*m+#*A,m^20,1+'1'A,m"#m4'031m .-0m 9$'"-1Zm m ^&)(O ,).#O *).O #,/-_m 7m /-,#/'O )23-*),/'O EO -*Em +#*-,'1m 08m FZGZm 0#1.#!2'4+#,2#_m ^3/3#2m 7m !-*YZm HFFJ\m '#2-m 7m !-*YZm HFFL\m -- #30m 7m !-*YZm HFFJ_Ym _mm *m!-,-!'+'#,2-m"#m1#!3#,!'1m"#m1m#1m!*4#m.0m*m1#*#!!'A,m"#m%#,#1m!,"'"2-1m .0m !0!2#0#1m "#m ',2#0<1m %0-,A+'!-Ym -,8*#8j #1m 7m !-* -0"-0#1m #,m HFFMm ^,#6-m_m.3 *'!0-,mIFYFFFm,3#41m1#!3#,!'1m"#m1m- 2#,'"1mm.02'0m"#m-!&-m %#,-2#!1m"#m!m#* -0"1mm.02'0m"#m+m#620>"-m"#m+3#1201m"#m$032-m#,m "'12',2-1m #12"'-1m "#m "#100-**-m 7m "#m 2#('"-1m ',$#!2"-1m !-,m .2A%#,-1Ym -,m *m - 2#,!'A,m "#m 1#!3#,!'1m "#m 1m 1#m .3"'#0-,m "#2#!20m ,3#4-1m .-*'+-0$'1+-1m 7m m .02'0m"#m#**-1m"#100-**0m,3#4-1m+0!"-0#1m+-*#!3*0#1m3+#,2,"-m*m1230!'A,m "#*m+.m%#,<2'!-m^#*#3m7m!-*YZmHFFO_m^,#6-m _Ym,mHFGGm-20-m#123"'-mm.02'0m"#mGKm %#,-2#!1m "#m !m "#m $032-1Zm $*-0#1Zm &-(1Zm 0>!#1Zm !-2'*#"-,#1Zm 7m !**-1m "#m !320-m GH &O'&9(O3O&O!(9'#O&O'&9(O (.,)/#9(O %#,-2'.-1m"#m+#*A,Zm.#0+'2'Am- 2#,#0mMGYKMMm1mm.02'0m"#m%#,-2#!1m#,0'/3#!'"1mm 7mHHYGMOm1mm.02'0m"#m%#,-2#!1m"#m!m#129,"0Ymm',2#%0!'A,m"#m#12-1m1m (3,2-m !-,m *-1m 1m "'1.-,' *#1m ,2#0'-0+#,2#m .#0+'2'Am - 2#,#0m 3,m 2-2*m "#m HJYJJJm 3,'%#,#1m ^*#.#2m 7m !-YZm HFGG_Ym #!'#,2#+#,2#m 1#m &,m %#,#0"-m 2+ '<,m "2-1m "#m j1#/m m .02'0m "#m "'12',2-1m %#,-2'.-1m 7m 2#('"-1m "#m +#*A,Zm 32'*'8,"-m .'0-1#!3#,!'!'A,m JKJm ^*,!m 7m !-*YYm HFGG\m -0 !&-m 7m !-*YYm HFGI\m -02,-7m 7m !-*YZm HFGG_m-m1#!3#,!'!'A,m+#"',2#m'm^*,!m7m!-*YZmHFGH_Ym _mmmmm m#* -0!'A,m"#m+'!0-m+20'!#1m"#mm^'#,),,3-_m&m1'"-m-20m&#00+'#,2m/3#m 1#m&m"#100-**"-m#,m+#*A,m7m/3#m.-02m',$-0+!'A,mm,'4#*m20,1!0'.2A+'!-m-m"#m #6.0#1'A,m"#m%#,#1m#,m2#('"-1m7m!-,"'!'-,#1m#1.#!>$'!1Ymm+'!0-m+20'8m"#m+#*A,m1#m "'1#@Am!-,mGMYKGFm3,'%#,#1m"#0'4"-1m"#mIIYJGNm1m^1!0#**j0#31m7m!-*YZmHFFO_Ym 12-1m1m$3#0-,m'1*"-1mm.02'0m"#m"'12',2-1m#12"'-1m"#m"#100-**-m"#m*m.*,2m-m #,m 1'23!'-,#1m + '#,2*#1m #1.#!>$'!1m ^-,89*#8j #1m 7m !-*YZm HFFM_Ym 0m 4*'"0m *m +'!0-m+20'8m1#m0#*'80-,m20#1m#6.#0'+#,2-1m!-,m"'12',21m+3#1201m"#m+#*A,Ym,m*m .0'+#0Zm 1#m !-+.0Am *m #6.0#1'A,m #,m $032-m ',+"30-m ^GKm ">1m "#1.3<1m "#m *m .-*','8!'A,_m!-,m*m#6.0#1'A,m"#m3,m+3#120m"#m$032-m+"30-m^JLm">1m"#1.3<1m"#m *m .-*','8!'A,_m #,m *m 40'#""m GGGm /3#m .#0+'2'Am !-+.00m *-1m !+ '-1m 20,1!0'.!'-,*#1m "30,2#m #*m "#100-**-m "#m $032-Ym ,m 3,m 1#%3,"m &' 0'"!'A,m 1#m !-+.0Am 2#('"-m "#m 0>8m "#1.3<1m "#m *m ',-!3*!'A,m !-,m #*m &-,%-m )()-*),-/-O (()(&&/-m!-,m2#('"-m"#m0>8m,-m',$#!2"-m#,m*m40'#""m0#1'12#,2#m//'#-m'&)O--*O %0#12'1m 2NGEm ',*+#,2#m #,m *m 2#0!#0m &' 0'"!'A,Zm 1#m !-+.0Am 3,m +3#120m "#m 2#('"-m"#m!-2'*#"-,#1m',$#!2"-1m.-0m#*m4'031m"#*m+-1'!-m"#*m.#.',-m^_m!-,m3,m +3#120m"#m2#('"-m,-m',$#!2"-m"#m*m40'#""m#,"0*Ym^1!0#**j0#31m7m!-*YZmHFFO_Ym #!'#,2#+#,2#m *m +'!0-m +20'8m "#m m 1#m &m 32'*'8"-m .0m "#1!3 0'0m !+ '-1m 20,1!0'.!'-,*#1m1-!'"-1mm*m0#1'12#,!'m*m4'031m"#*m+-1'!-m"#m*m1,">m^_m #,m*m!!#1'A,mjGKKGm^-,8*#8j #1m7m!-*YZmHFGH_m-m*m0#1'12#,!'mm)()-*),-/-O (()(&&/-m^-'%m#2m*mHFGI_Ym _mm ,m *-1m B*2'+-1m @-1m 1#m &,m "#100-**"-m 3,m !-,(3,2-m "#m 2<!,'!1m .*'! *#1m m *m %#,A+'!m$3,!'-,*Ym,m"#m*1m+91m'+.-02,2#1m#1m#*m"#100-**-m"#m.*2$-0+1m.0m *m!0!2#0'8!'A,m"#m+32,2#1m+#"',2#mYm1m.- *!'-,#1m"#mm1-,m .- *!'-,#1m"#m+32,2#1m#* -0"1mm.02'0m"#m*m+32%#,'8!'A,m"#m*1m1#+'**1m-m #*m .-*#,Zm !-,m 3,m %#,2#m +329%#,-Ym m .0'+#0m .03# m "#m +32%#,#'8!'A,m m %0,m #1!*m #,m +#*A,m 1#m &'8-m #,m *m *>,#m -7m '80#j#*Zm 3,m +#*A,m 2'.-m *'Zm "#m *m /3#m 1#m GI (.,)/#9( El melón y la genómica de melón - 234'#0-,m IFFFm $+'*'1m HYm -1m #123"'-1m $#,-2>.'!-1m "#2#!20-,m +32!'-,#1m #,m "'12',2-1m#12"'-1m"#m"#100-**-m7m2#('"-1Zm',!*3'"-1m!-2'*#"-,#1Zm&-(1Zm$*-0#1m7m$032-1m ^"+-0m 7m !-*YZm HFFM_Ym ',m #+ 0%-Zm *m .0'+#0m .- *!'A,m "#m m %#,#0"m #,m #12m#1.#!'#m#1m*m/3#m1#m.0#1#,2m#,m#12#m20 (-Zm- 2#,'"mm.02'0m"#m3,m*>,#m"- *#m &.*-'"#m LHjGGIm "#m +#*A,m 2'.-m b'#*m "#m .-cm !-,m 3,m 2-2*m "#m IHLNm $+'*'1m Hm ^-,8*#8j-m 7m !-*YZm HFGG_Ym ,m HFGFm 1#m .3 *'!Am 3,m ,3#4m .- *!'A,m #,m *m !3*m 1#m 32'*'8Am 3,m 40'#""m "#m +#*A,m 2'.-m ",(.#-m ^&0-,-_m .0m "#100-**0m 3,m .*2$-0+m "#m m "#m JFHIm $+'*'1m HYm ,m #12m .- *!'A,m 1#m 31!0-,m +32,2#1m #,m GGm %#,#1Zm '+.*'!"-1m #,m #*m .0-!#1-m "#m +"30!'A,m "#m $032-m 7m #,m *m "#2#0+',!'A,m"#*m1#6-m"#m*1m$*-0#1m^&+,'m7m!-*YZmHFGF_m T BMBMFMCTTTTT *m +#*A,m #1m 3,m #1.#!'#m "'.*-'"#m !-,m 3,m ,B+#0-m 91'!-m "#m !0-+-1-+1m ,SGHm ^H,SH6SHJ_m^&'2)#0ZmGOML_Ym*m2+@-m"#*m%#,-+m#1m"#m.0-6'+"+#,2#mJKFm m ^03+3%,2&,ZmGOOG_Zm2+@-m1'+'*0m*m%#,-+m"#*m00-8m^JGOm _m7m!1'm!320-m 4#!#1m#*m%#,-+m"#m,#)*-#-O."&#(m^GHKm _Ym,m#*m@-mHFFOm1#m','!'Am#*m.0-7#!2-m m!-,m#*m- (#2'4-m"#m- 2#,#0m3,m -00"-0m"#m*m1#!3#,!'m"#*m%#,-+m "#*m +#*A,Ym !23*+#,2#Zm #*m %#,-+m "#*m +#*A,m 7m &m 1'"-m .3 *'!"-Zm & '<,"-1#m .-"'"-m #,1+ *0m .0-6'+"+#,2#m 3,m NIZIPm "#*m %#,-+Zm /3#m !-,2'#,#m HMYJHMm %#,#1m^0!'j1m7m!-*YZmHFGH_Ymm m BMBMFMDTTTST ,m *m B*2'+m "<!"Zm 1#m &m .-"'"-m - 2#,#0m *m 1#!3#,!'m "#*m %#,-+m "#m "'12',2-1m -0%,'1+-1m ^&22.[iim 555Y,! 'Y,*+Y,'&Y%-4i#,-+#1_Ym ',m #+ 0%-Zm 2-"4>m &-7m 1#m #129,m "#100-**,"-m &#00+'#,21m .0m .-"#0m #6.*-20m #12m ',$-0+!'A,Ym -1m %#,-+1m#129,m1#!3#,!'"-1m.#0-m2-"4>m,-m1#m1 #m!-,m#6!2'23"m!A+-m'"#,2'$'!0m *m $3,!'-,*'""m "#m 2-"-1m *-1m %#,#1m /3#m &,m 1'"-m ,-2"-1Ym -0m *-m 2,2-Zm #,m *m +7-0>m "#m *-1m %#,-+1m 1#!3#,!'"-1m #6'12#m 3,m *2-m .-0!#,2(#m "#m %#,#1m ,-2"-1m '-',$-0+92'!+#,2#m 1',m $3,!'A,m "#+-120"Zm "#,-+',"-1m b.322'4#cm -m b3,),-5,cm ^A.#8j0m 7m !-*YZm HFFL_Ym 0m .-"#0m ,-20m 3,m %#,-+m 1#m !-+ ',,m 91'!+#,2#m20#1m+<2-"-1[mG_m<2-"-1mO#(#.#)m"#m.0#"'!!'A,m"#m%#,#1m/3#m.#0+'2#,m .0#"#!'0m *m .0#1#,!'m "#m 3,m %#,Ym H_m #"',2#m &-+-*-%>m !-,m 1m "#m *m +'1+m #1.#!'#YmI_m#"',2#m&-+-*-%>m!-,m.0-2#>,1m"#m*1m!3*#1m7m1#m&m"#2#0+',"-m13m $3,!'A,m7m/3#m#129,m.0#1#,2#1m#,m*1m 1#1m"#m"2-1Ymm0m**#%0mm"#1!'$00m*m$3,!'A,m "#m !"m %#,m ,-2"-m #,m #*m %#,-+m &!#m $*2m "#100-**0m -20-1m +<2-"-1m !-+-m .3#"#,m1#0m*1m2<!,'!1m"#m%#,<2'!m',4#01Ymmm GJ &O'&9(O3O&O!(9'#O&O'&9(O (.,)/#9(O "#+91Zm!-,m*m1#!3#,!'!'A,m"#m%#,-+1m1#m&m.-"'"-m- 1#040m/3#m3,m%0,m.02#m "#*m %#,-+m !-,2'#,#m 1#!3#,!'m ,-m !-"'$'!,2#Ym -0m #(#+.*-Zm #,m #*m %#,-+m &3+,-m 1A*-m #*m GZKPm #1m !-"'$'!,2#m .0m .0-6'+"+#,2#m HKYFFFm %#,#1m ^-*$1 #0%Zm HFGG_Ym 12-m**#4Am&!#m3,-1m@-1mm"#$','0m#*mbm 130cm-m#*mb(3,)mcYm#mm"#,-+',Am 1>m m 2-"1m /3#**1m 1#!3#,!'1m "#*m %#,-+m /3#m ,-m !-"'$'!,m .0m 3,m .0-2#>,m -m 1#!3#,!'1m 0#%3*"-01Zm +7-0'20'+#,2#m 20,1.-1-,#1m -m #*#+#,2-1m 0#.#2'2'4-1Ym ,'!'*+#,2#Zm 1#m .#,1 m /3#m #12m .02#m "#*m %#,-+m ,-m 2#,>m ,',%3,m $3,!'A,Zm 1',m #+ 0%-Zm1#m&m"#+-120"-m/3#m.02#m"#m#121m1#!3#,!'1m1#m20,1!0' #,m7m*%3,1m"#m #**1m 0#%3*,m *m #6.0#1'A,m "#m *-1m %#,#1m ^&#m m ^7!*-.#"'m $m m *#+#,21_m 0-(#!2m -,1-02'3+Zm HFFJ_m -m /3#m 1-,m '+.-02,2#1m .0m #12 '*'80m !'#021m #1203!2301m!-+-m1-,m*-1m2#*A+#0-1m7m*-1m!#,20A+#0-1m^#$$#0,'!)ZmHFFO_Ymm GK (.,)/#9( Mutaciones en el ADN m T BMCTTT T BMCMBTTTT #$','+-1m +32!'A,m !-+-m 3,m !+ '-m #,m *m ',$-0+!'A,m %#,<2'!m ^_Ym 1m +32!'-,#1m 2'#,#,m '+.-02,!'m .-0/3<m .-02,m 40',2#1m *<*'!1m 7m 40',2#1m $3,!'-,*#1m.0-4-!,"-m$#,-2'.-1m"'12',2-1m"#*m$#,-2'.-m1'*4#120#Ymm+32!'-,#1m1-,m &#0#" *#1Zm 3,/3#m #,m -0%,'1+-1m +3*2'!#*3*0#1m &7m /3#m "'12',%3'0m #,20#m +32!'-,#1m.0-"3!'"1m#,m*-1m%+#2-1m7m*1m.0-"3!'"1m#,m*1m!<*3*1m1-+92'!1Ym1m +32!'-,#1m .0-"3!'"1m #,m *-1m %+#2-1m 1#m 20,1$#0'09,m m *m 1'%3'#,2#m %#,#0!'A,m +'#,201m/3#m*1m.0-"3!'"1m#,m*1m!<*3*1m1-+92'!1m1A*-m$#!20,m*m',"'4'"3-m/3#m *1m."#!#m7m,-m2#,"09,m3,m#$#!2-m&#0#"'20'-Ym m$0#!3#,!'m"#m+32!'A,m#,m*-1m%#,#1m"#.#,"#m"#m40'-1m$!2-0#1Zm3,/3#m*-1m+91m '+.-02,2#1m 1#,m *m *-,%'23"m "#*m %#,m 7m #*m &#!&-m "#m !-,2#,#0m 8-,1m !-,m +91m .0- '*'""m"#m1#0m+32"1m^.-0m2#,#0m3,m*2m.0- '*'""m"#m+32!'A,m"# '"-mm 13m !-+.-1'!'A,m /3>+'!_Zm !-+-m 1-,m *1m 0#%'-,#1m .m ^03#, 3+m 7m !-*YZm GONGZm -,2#*-,#Zm GOON_Ym m $0#!3#,!'m !-,m *m /3#m *m m .-*'+#01m ',1#02m 3,m 1#m #/3'4-!"m #,m ++>$#0-1m #1m "#m G6GFjOm ^3+0m 7m !-*YZm HFFM_m +'#,201m /3#m *m $0#!3#,!'m #,m *-1m 4'031m "#m m #1m "#m G6GFjLm^0-+1m 7m *#,Zm HFGF_Ym ,m .*,21m ,-m .0#!#m& #0m3,m#123"'-m.0#!'1-m"#m#12-1m4*-0#1Ymm 1m +32!'-,#1m ,230*#1m .-02,m 40',2#1m *<*'!1m /3#m .3#"#,m .-020m ,3#41m .0-.'#""#1m m 3,m #1.#!'#Ym ,m #(#+.*-m +.*'+#,2#m #123"'"-m #,m .*,21m 1-,m *1m 40',2#1m*<*'!1m"#*m%#,m>Ym,m+#*A,Zm1>m!-+-m#,m.'+'#,2-m^3$$#*m7m!-*YZmHFFH_Zm %3'1,2#m^-m7m!-*YZmHFFJ_m7m-201m#1.#!'#1m1#m&,m"#2#!2"-m+32!'-,#1m,230*#1m#,m #*m %#,m >m 0#1.-,1 *#1m "#m *m 0#1'12#,!'m m "'12',2-1m 4'031Zm !-+-m 4#0#+-1m +91m "#*,2#Ym ,m 2-"-1m *-1m !1-1m #*m 4'031m ,-m .3#"#m ',2#0!!'-,0m !-,m #*m $!2-0m "#m ','!'!'A,m"#m*m20"3!!'A,mJm7m.-0m*-m2,2-m,-m.3#"#m0#.*'!01#m#m',$#!20m*m.*,2m ^'#2-m7m!-*YZmHFFL_Ymm T BMCMBMBTTTTT 1m 1#1m ,'20-%#,"1m 1-,m 131!#.2' *#1m m 13$0'0m *#1'-,#1m #1.-,29,#1m #,m 13m !-,$-0+!'A,m /3>+'!Ym 121m *2#0!'-,#1m .3#"#,m .0-"3!'0m 40'-1m #$#!2-1m #,m *m !"#,m +-*"#m $#!2,"-m m *m !-+.*#+#,20'#""m "#m *m +'1+m -m .0-4-!,"-m -20-1m 2'.-1m"#m*2#0!'-,#1m!-+-m*1m',1#0!'-,#1m-m*1m"#*#!'-,#1Ymm m GL /.#)(-O(O&OOO (.,)/#9(O _mmmm MBT$!(#.1T T+ 1T%.0, 1T2 32.,:0(" 1T "m 3,m "#m *1m 1#1m "#*m m .3#"#m #6'12'0m #,m *m ,230*#8m #,m "-1m $-0+1m 232-+<0'!1Ym 1m "'$#0#,!'1m /3>+'!1m #,20#m *1m "-1m $-0+1m 232-+<0'!1m !-,1'12#,m #,m #*m "#1.*8+'#,2-m "#m 92-+-1m "#m &'"0A%#,-m /3#m +'%0,m &!'m .-1'!'-,#1m +91m ',#12 *#1Ym -0+*+#,2#Zm #,m #*m m 1#m #,!3#,20m *m $-0+m .)Zm +'#,201m /3#m *1m $-0+1m#'#()m-m()&m1-,m&12mGFYFFFm4#!#1m+91m',#12 *#1m^-,2#*-,#ZmGOON_Ym6'12#,m "-1m2'.-1m"#m0#!!'-,#1m232-+<0'!1Zm*m#2-k#,A*'!m^"-,"#m3,m%03.-m!#2-m^S_m1#m !-,4'#02#m#,m3,m%03.-m#,-*m^j__m-m+',j+',m^"-,"#m#*m%03.-m+',m^S_m1#m !-,4'#02#m #,m 3,m %03.-m +',-m ^jH__Ym 1m $-0+1m 232-+<0'!1m ',#12 *#1m 2'#,#,m #1.#!>$'!+#,2#m *2#0"1m *1m .0-.'#""#1m "#m !-+.*#+#,20'#""m #,m *m !"#,m "#m m$#!2,"-m#,m13m0#.*'!!'A,Ym,m*m *mGYGm.3#"#m- 1#0401#m!-+-m!+ 'm*m !-+.*#+#,20'#""m"#m*1m 1#1Y T !+ T BMBOT #.0#1#,2!'A,m "#m *1m $-0+1m 232-+<0'!1m "#m !"m 1#m /3#m $-0+m #*m m 7m "#m *m !-+.*#+#,20'#""m/3#m"/3'#0#,Ym m m -0+m 32-+<0'!m "-.2m .0-.'#""#1m "#m -+.*#+#,2m !-,m gm m m gm m m gm m m gm m m m 'm#,m*m!"#,m+-*"#m/3#m1#m#129m0#.*'!,"-m&7m3,m$-0+m232-+<0'!m"#m3,m 1#m 1#m.3#"#m.0-"3!'0m3,m#00-0m"#m!-+.*#+#,20'#""m.0-4-!,"-m*m',!-0.-0!'A,m"#m 3,m 1#m /3#m ,-m #1m *m !-00#1.-,"'#,2#m m *m 1#!3#,!'m -0'%',*m 7m #,m !-,1#!3#,!'m .0-"3!'0m3,m+32!'A,Ym12-1m!+ '-1m.3#"#,m1#0m20,1'!'-,#1m 1"-1m#,m#*m!+ '-m "#m3,m.30',mm-20m.30',m^Z_m-m"#m3,m.'0'+'"',mm-20m.'0'+'"',m^Zm_Ym1m !-,1#!3#,!'1m"#m#12-1m!+ '-1m"#.#,"#,m"#m*m.-1'!'A,m7m"#*m2'.-m"#m!+ '-m/3#m1#m .0-"38!m 1>m !-+-m "#m 13m *-!*'8!'A,m ^#,m 0#%'A,m #6A,'!m -m ',20A,'!_Ym 'm *m 1#m !+ '"m1#m#,!3#,20m#,m0#%'A,m#6A,'!m7m,-m.0-4-!m3,m!+ '-m"#m+',-9!'"-m#,m *m 20"3!!'A,m "#*m !-"A,Zm <12#m 1#09m 3,m !+ '-m 1'*#,!'-1-Ym -0+*+#,2#Zm #12#m 2'.-m "#m !+ '-m 1#m .0-"3!#m !3,"-m +32m *m 2#0!#0m 1#m "#*m !-"A,m .3#12-m /3#m #*m !A"'%-m GM (.,)/#9( Mutaciones en el ADN %#,<2'!-m#1m"#%#,#0"-Ym'm#*m!+ '-m"#m 1#m.0-4-!m3,m!+ '-m"#m+',-9!'"-m1#m "#,-+',m !+ '-m 1312'232'4-m -m ,-m 1',A,'+-EO ',*+#,2#Zm 1'm #*m !+ '-m "#m 1#m .0-"3!#m3,m!-"A,m12-.m1#m"#,-+',m!+ '-m1',m1#,2'"-m""-m/3#m.-"0>m"#2#,#01#m *m20"3!!'A,m**>m"-,"#m1#m"#m*m+32!'A,m7m#,m!-,1#!3#,!'Zm,-m.-"#0m1',2#2'80m*m .0-2#>,m #,m 13m 2-2*'""Ym -1m !+ '-1m 1312'232'4-1m 7m 1',m 1#,2'"-O1-,m *-1m +91m %04#1m 7m/3#m.3#"#,m$#!20m1#0'+#,2#mm*m#1203!230m7m.-0m*-m2,2-mm*m$3,!'-,*'""m"#m *m.0-2#>,Ym MCT-1$0"(.-$1T7T#$+$"(.-$1T ,m "#m *1m +32!'-,#1m #1.-,29,#1m +91m & '23*#1m #,m 1#!3#,!'1m 0#.#2'"1m *0%1m 1-,m*1m"#*#!'-,#1m"#m$0%+#,2-1Ym20#'1',%#0m7m5#,m^GONK_m$-0+3*0-,m3,m+-"#*-m /3#m #6.*'!m *-1m !+ '-1m "#m $1#m "30,2#m *m 1>,2#1'1m "#m Zm *-1m !3*#1m !+ ',m *m .32m "#m *m *#!230m "#m *m .0-2#>,Ym 'm "30,2#m *m 0#.*'!!'A,m #,m *m !"#,m +-*"#m 2#,#+-1m3,m1#!3#,!'m!-,m3,m0#.#2'!'A,m"#m,3!*#A2'"-1m.3#"#,m-!300'0m"-1m!1-1Ym *m .0'+#0-m #1m /3#m "30,2#m *m 0#.*'!!'A,m 1#m !0##m 3,m *8-m #,m *m !"#,m 0#.*'!"Ym m 0#.*'!!'A,m 1#%3'09m 13m !301-m 7m $',*+#,2#Zm .3#12-m /3#m #*m *8-m &m .0-4-!"-m 3,m !-00'+'#,2-m"#m*m!"#,m0#.*'!"Zm1#m@"'09m3,m,3!*#A2'"-m+91m"#m*-1m/3#m&7m#,m *m!"#,m+-*"#Ym*m1#%3,"-m!1-m#1m1'm#*m*8-m-!300#m#,m*m!"#,m+-*"#Ym*m!0#01#m 3,m !-00'+'#,2-m #,m *m !"#,m +-*"#Zm *m !"#,m /3#m 1#m #129m 0#.*'!,"-m 2#,"09m 3,m ,3!*#A2'"-m+#,-1m.3#12-m/3#m"-,"#m1#m&m.0-"3!'"-m#*m*8-m,-m1#m&m@"'"-m*m 1#m !-+.*#+#,20'Ym ,m #*m .0'+#0m !1-m 1#m - 2#,"09m 3,m !"#,m !-,m 3,m ,3!*#A2'"-m "#m +91Zm .-0m *-m 2,2-m 1#m & 09m .0-"3!'"-m 3,m ',1#0!'A,Ym ,m #*m 1#%3,"-m !1-m *m !"#,m 2#,"09m3,m,3!*#A2'"-m"#m+#,-1m7m.-0m*-m2,2-m1#m& 09m.0-"3!'"-m3,m"#*#!'A,Ym m _mmmmmm T MBT$1 ,(- "(>-T -1m ,3!*#A2'"-1m .3#"#,m .#0"#0m #*m %03.-m +',-m .-0m "#1+',!'A,m -6'"2'4m .0-4-!,"-m 3,m !-+.*#+#,20'#""m #00A,#m #,m *m 0#.*'!!'A,m "#*m Ym "-m /3#m *m "#1+',!'A,m "#m !'2-1',m .0-"3!#m 30!'*-Zm *m !<*3*m 2'#,#m 1'12#+1m "#m 0#.0!'A,m .0m0#.00m#12#m#00-0Ym1m%*3!-1'*11m"#m30!'*-m"#mm0#!-,-!#09,m*-1m30!'*-1m #,m *m !"#,Zm *-1m #1!',"'09,m 7m #*m &3#!-m 1#09m 0#**#,"-m .-0m *m m .-*'+#01m m 7m $',*+#,2#m*'%"-m.-0m3,m*'%1Ym'm#*m1'12#+m"#m0#.0!'A,m,-m"#2#!2m7m0#.0m#12#m #00-0Zm #,m *m !"#,m +-*"#m .0#!#09m 3,m 30!'*-m /3#m .-12#0'-0+#,2#m #+.0#(09m !-,m 3,m"#,',m#,m4#8m"#m*m%3,',m/3#m*#m!-00#1.-,"#0>m^* #021m7m!-*YZmHFFL_Ym T GN /.#)(-O(O&OOO (.,)/#9(O T MCT$1/30(-(8 "(>-T m"#1.30','8!'A,Zm'+.*'!m*m',2#003.!'A,m"#*m#,*!#m%*3!-1>"'!-m#,20#m*m 1#m7m*m "#1-6'0' -1m7m*m.<0"'"m.-12#0'-0m"#m3,m0#1'"3-m"#m%3,',m-m"#,',m"#*mYm'm #12m *#1'A,m .#01'12#Zm !-,"3!#m m 3,m "@-m %#,<2'!-m '+.-02,2#m .-0/3#m *-1m 1'2'-1m 1',m .30',m /3#m 1#m -0'%',,m ,-m .3#"#,m #,*80m !-,m 13m 1#m !-+.*#+#,20'm "30,2#m *m 0#.*'!!'A,Ym ',m #+ 0%-Zm 1'12#+1m "#m 0#.0!'A,m #$'!!#1m #*'+',,m *-1m 1'2'-1m 1',m .30',1Ym(-m!'#021m!'0!3,12,!'1m1#m.3#"#m',1#020m3,m 1#m#,m3,m1'2'-m1',m.30',\m !-,m$0#!3#,!'m#12-m"m!-+-m0#13*2"-m3,m+32!'A,m^* #021m7m!-*YZmHFFL_Ym MDT6(# "(>-T *m +#2 -*'1+-m #0- '-m %#,#0Zm !-+-m 13 .0-"3!2-Zm !'#021m #1.#!'#1m !2'41m "#m -6>%#,-Zm!-+-m0"'!*#1m13.#0A6'"-m^Hj_Zm.#0A6'"-m"#m&'"0A%#,-m^HH_m7m0"'!*#1m &'"0-6'*-m^j_Ym-"1m#**1m!31,m*#1'-,#1m-6'"2'41m#,m#*mm/3#m",m*3%0mm +32!'-,#1Zm*1m+91m$0#!3#,2#1m1-,mmmm.-0m-6'"!'A,m"#m*m%3,',m^* #021m7m!-*YZm HFFL_YT m GO (.,)/#9( Mutagénesis inducida m m BMDTTT m BMDMBTTTT #m "#,-+',m +32%<,#1'1m m *m .0-"3!!'A,m ',2#,!'-,"m "#m 40' '*'""m %#,<2'!m m 204<1m "#m +<2-"-1m $>1'!-1m -m /3>+'!-1Ym m 32'*'8!'A,m "#m #12-1m +<2-"-1m .0-4-!m !+ '-1m *m 80m #,m #*m Zm 7m #,m !-,1#!3#,!'Zm 2+ '<,m #,m *-1m %#,#1m 7m #,m #*m -0%,'1+-Ym,m.*,21Zm*m+32%<,#1'1m%#,#0*+#,2#m1#m.*'!m#,m*1m1#+'**1m3,/3#m #,m *%3,1m #1.#!'#1m !-+-m #*m +>8m 1#m &m .*'!"-m #,m #*m .-*#,Ym 12#m +<2-"-m '+.*'!m /3#m &!#m $*2m #1.#00Zm *m +#,-1Zm m *m 1#%3,"m %#,#0!'A,m .0m - 1#040m #$#!2-1m $#,-2>.'!-1m^-"7+m7m$8ZmHFFI_Ymm m +32%<,#1'1m .3#"#m 1#0m "'0'%'"m -m ',"3!'"Ym *m .0'+#0m 2<0+',-m &!#m 0#$#0#,!'m m /3#**1m +32!'-,#1m .0#!'11m /3#m 1#m .0-4-!,m #,m 3,m %#,m "#1#"-Ym *m 1#%3,"-Zm #,m !+ '-Zm&!#m0#$#0#,!'mm*m+32%<,#1'1m',"3!'"m.-0m+329%#,-1m/3>+'!-1m-m$>1'!-1m /3#m.0-4-!,m!+ '-1m*m80m7m"#m3,m+,#0m%#,#0*'8"m#,m2-"-m#*m%#,-+Ym-1m .0'+#0-1m ',4#12'%"-0#1m /3#m .0-"3(#0-,m 02'$'!'*+#,2#m +32!'-,#1m #,m #*m m $3#0-,m 3**#0m 7m 2"*#0m #,m #*m GOHMm 7m GOHNm 0#1.#!2'4+#,2#m !-,m *m "#+-120!'A,m "#*m #$#!2-m+32%<,'!-m"#m*-1m07-1mm#,m+>8Zm!# "m7m,)-)*"#&O'&()!-.,m^* #021m7m !-*YZmHFFL_Ym m BMDMCTTTTT TT m +#(-0m %#,<2'!m 1#m 1m #,m - 1#040m 7m 1#*#!!'-,0m *-1m +#(-0#1m ',"'4'"3-1m #,m $3,!'A,m "#m *-1m !0!2#0#1m "#m ',2#0<1m .0m .-12#0'-0+#,2#m $'(0m #1#m !09!2#0m #,m 3,m .- *!'A,Ym#m#12#m+-"-m1#m"#100-**,m.- *!'-,#1m!-,m!0!2#0#1mA.2'+-1m.0m3,m - (#2'4-m!-+#0!'*Ymm+#(-0m%#,<2'!m31m!-+-m&#00+'#,2m*m40' '*'""m%#,<2'!m #6'12#,2#m#,20#m.- *!'-,#1m7m#,20#m',"'4'"3-1Ym12m$3#,2#m"#m40' '*'""m1#m%#,#0m #1.-,29,#+#,2#m!A+-m0#13*2"-m"#m#00-0#1m.0-4-!"-1m#,m*m"'4'1'A,m!#*3*0m7m#,m #*m 1'12#+m "#m 0#.0!'A,m "#*m m ^*m 0"'!'A,m 1-*0m 2'#,#m 3,m '+.-02,2#m ..#*m #,m #12-1m #00-0#1_Ym 1m +32!'-,#1m ,230*#1m ,-m 1-,m 3,",2#1m 7m +#,-1m 3,m !3,"-m **#%,mm$#!20mm*m$3,!'-,*'""m"#m*1m.0-2#>,1m^#,m&3+,-1m*m21m"#m+32!'A,m #1m "#*m -0"#,m "#m GFjLm +32!'-,#1i*-!31i%#,#0!'A,Zm 3,/3#m .3#"#m 40'0m "#,20-m "#*m 0,%-m"#mGFjJm&12mGFjMm"#.#,"'#,"-m"#*m2+@-m"#*m%#,m^-*%',ZmHFFO__Ym1m.-0m#**-m /3#m m .0',!'.'-1m "#*m 1'%*-m m 1#m #+.#80-,m m .*'!0m 2<!,'!1m "#m +32%<,#1'1m .0m .0-"3!'0m+91m40' '*'""m7m"#m3,m+-"-m+91m09.'"-Ymm.0',!'.'-1m"#m*-1m@-1mKFm1#m HF /.!6(-#-O#(/#O (.,)/#9(O #+.#80-,mm310m!-+#0!'*+#,2#m!3*2'4-1m+#(-0"-1mm204<1m"#m*m+32%<,#1'1Ymm m ^))O (O !,#/&./,O ,!(#4.#)(_m #+.#8Am m "-!3+#,20m 2-"-1m *-1m !3*2'4-1m - 2#,'"-1m .-0m +32%<,#1'1m 7m #,m GOOJm *m *'12m !-,2#,>m +91m "#m GNFFm !3*2'40#1m ^555Y$-Y-0%_Ym!23*+#,2#m*m+7-0>m"#m!3*2'4-1m#6.*-2"-1m#,m#*m+3,"-m1-,m7i-m .0-4'#,#,m"#m!038+'#,2-1m"#m*-1m.0'+#0-1m!3*2'40#1m+32"-1Ym-0m#(#+.*-Zm#,mGOOJm *m m "#2**Am /3#m #*m MFPm "#m 20'%-m "30-m ^,#.#/'O -.#0/'_m !3*2'4"-m #,m 2*'m .0-4#,>m"#m!3*2'4-1m+32"-1Ymm m+32%<,#1'1m/3>+'!m7m*m0"'!'A,m'-,'8,2#m&,m1'"-m32'*'8"1m#$'!'#,2#+#,2#m .0m%#,#00m40' '*'""m%#,<2'!m/3#m.-12#0'-0+#,2#m&m1'"-m32'*'8"m#,m*m+#(-0m %#,<2'!Ym 121m +#2-"-*-%>1m 2'#,#,m *m 4#,2(m "#m 1#0m +91m #!-,A+'!1m 7m *m +'1+-m 2'#+.-Zm +91m !#.2"1m 1-!'*+#,2#m /3#m *m 2#!,-*-%>m 20,1%<,'!Ym !23*+#,2#Zm m 204<1m "#m #12-1m +<2-"-1m #6'12#,m HYJHNm 40'#""#1m "#m !3*2'4-1m +32%#,'8"-1m #,m #*m +3,"-ZmKFGm"#m#**-1m#,m00-8m^&22.[ii555j+4"Y'#Y-0%i_Ym T BMDMDTTTTT ,m+329%#,-m#1m3,m.0-"3!2-m,230*m-m#* -0"-m.-0m#*m&-+ 0#m/3#m.3#"#m*2#00m*m #1203!230m -m *m 1#!3#,!'m "#*m Ym -"#+-1m !*1'$'!0m #12-1m %#,2#1m +329%#,-1m #,m $3,!'A,m "#m !A+-m .0-"3!#,m *1m *#1'-,#1m 7m 1#m +#"',2#m 3,m +#!,'1+-m $>1'!-m -m /3>+'!-Ymm+32%<,#1'1m+#"',2#m+32,2#1m/3>+'!-1m7m0"'!'-,#1m'-,'8,2#1m1#m&m 31"-m #,m .*,21m #,m %#,<2'!m "'0#!2m ^&'0*#7m 7m !-*YZm GOOH_Ym 12#m 2'.-m "#m +<2-"-1m 2'#,#,m !'#021m 4#,2(1m #,m !-+.0!'A,m !-,m *m +32%<,#1'1m ',1#0!'-,*Zm 7m /3#m %#,#0,m "'4#011m 1#0'#1m *<*'!1Zm ',"3!#,m +32!'-,#1m !-,m *2m $0#!3#,!'m 7m 1-,m .*'! *#1m m "'4#011m #1.#!'#1m ^."&77m 7m !-*Zm HFGG_Ym -0m *-m %#,#0*Zm *m +32%<,#1'1m/3>+'!m.0-"3!#m+32!'-,#1mm"'12',2-1m,'4#*#1Zm7m1#,m+32!'-,#1m1',m 1#,2'"-m -m +32!'-,#1m 1312'232'41Ym ,m !+ '-Zm *m +32%<,#1'1m +#"',2#m 0"'!'A,m '-,'8,2#m!-123+ 0mm.0-"3!'0m"#*#!'-,#1m!0-+-1A+'!1Ym-0m*-m2,2-Zm*m1#*#!!'A,m "#*m +329%#,-m "# #m 101#m #,m *m #$'!'#,!'m 7m *m #1.#!'$'!'""m .0m ',"3!'0m +32!'-,#1m 7m #,m *m *2m .0- '*'""m "#m #,!-,200m #*m 2'.-m "#m +32!'A,m "#1#"m ^ *m GYH_Ym + '<,m #1m '+.-02,2#m !-,-!#0m #*m 2'.-m "#m +32!'A,m /3#m .0-"3!#m #*m +329%#,-m.0m.-"#0m1#*#!!'-,0m#*m+<2-"-m"#m"#2#!!'A,m+91m#$'!'#,2#m^--0,,##$m7m !-*ZmGONH_Ymm m m m m HG (.,)/#9( Mutagénesis inducida m !+ TBMCOm#13+#,m"#m*-1m+329%#,-1m+91m& '23*#1m!-,m13m+#!,'1+-m"#m!!'A,m7m#*m2'.-m"#m+32!'A,m /3#m.0-"3!#,Ym m 31 R,329&$-.T $" -(1,.T (/.T#$T,32 "(>-T/0.#3"(# T 00-0#1m"#m0#.*'!!'A,m7m"#m 1.-,29,#m *-1m+#!,'1+-1m"#m -"-m2'.-m"#m+32!'-,#1m 0#.0!'A,m"#*mm Hj+',-.30',m 1#m,9*-%m jmmjm7mjmmjm20,1'!'-,#1m Kj 0-+30-30!'*-m 1#m,9*-%m jmmjm7mjmmjm20,1'!'-,#1m 2'*m#2,-m %#,2#m*/3'*,2#Zm%#,#0m 3*$-,2-m^_m Lj+#2'*%3,',m ^H_m jmmjm20,1'!'-,#1m 7-0+#,2#m!+ '-1mjmmjm "'!'A,mm >+#0-1m"#m.'0'+'"',m 20,1'!'-,#1Zm"#*#!'-,#1Zm!+ '-1m"#m .32m"#m*#!230m^+#,-1m$0#!3#,2#_mm 7-1mm "'!'A,m'-,'8,2#m 0-+30-m"#m#2'"'-m %#,2#m',2#0!*,2#m #*#!'-,#1m!0-+-1A+'!1m + '-1m"#m.32m"#m*#!230Zm "3.*'!!'-,#1m7m"#*#!'-,#1m m m m BMDMDMBTTT #.#,"'#,"-m "#*m +-"-m "#m !!'A,m -m +#!,'1+-1m "#m *-1m %#,2#1m /3>+'!-1m +32%<,'!-1Zm.-"#+-1m"'12',%3'0m20#1m%03.-1m"'12',2-1[m _mmm 1m 1#1m ,9*-%1m 1-,m #1203!2301m /3>+'!1m +37m 1#+#(,2#1m m *1m 1#1m ,'20-%#,"1m 7m 1#,m .30',1m -m .'0'+'"',1m 7m /3#m .-0m *-m 2,2-m m .3#"#,m 1312'23'0m m <121m#m',!-0.-001#m#,m#*mm"30,2#m*m0#.*'!!'A,m7m.-12#0'-0+#,2#m.0-4-!0m3,m +*m #+.0#(+'#,2-m "#m 1#1Zm .#0.#23,"-m 3,m +32!'A,m #,m *m 1#!3#,!'Ym -1m #(#+.*-1m"#m#12-1m%#,2#1m1-,[m jKj 0-+30-30!'*-[m !-+.3#12-m 02'$'!'*m 31"-m #,m ',4#12'%!'A,Ym 3m 1#+#(,8mm*m 1#m,'20-%#,"m2'+',m&!#m/3#m#+.0#(#m!-,m"#,',Ym jHj+',-.30',[m +-*<!3*m 1#+#(,2#m m *m "#,',m 7m .-0m *-m 2,2-m .0-4-!m #+.0#(+'#,2-m!-,m2'+',m-mm4#!#1Zm+#,-1m$0#!3#,2#+#,2#Zm!-,m!'2-1',m ^* #021m7m!-*YZmHFFL_Ym m m HH /.!6(-#-O#(/#O (.,)/#9(O _mmmmmm 6'12#,m 40'-1m %#,2#1m /3#m .0-4-!,m *2#0!'-,#1m #,m *m #1203!230m 7i-m #,m #*m #+.0#(+'#,2-m"#m*1m 1#1m,'20-%#,"1Ym'20#+-1m*-1m#(#+.*-1m"#m/3#**-1m+91m 31"-1[mm j!'"-m ,'20-1-[m .0-4-!m "#1+',!'A,m "#m !'2-1',m m 30!'*-Zm "#m +#2'*!'2-1',mm2'+',m7m"#m%3,',mm-20m 1#m,'20-%#,"m*-m/3#m.0-4-!m 20,1'!'-,#1mYm j%#,2#1m */3'*,2#1[m *-1m %#,2#1m */3'*,2#1m $3#0-,m *m .0'+#0m !*1#m "#m +329%#,-1m #,m 1#0m "#1!3 '#02-1m !3,"-m 3#0 !&m 7m - 1-,m ^GOJL_m "#1!3 0'#0-,m *-1m #$#!2-1m +32%<,'!-1m "#*m b%1m +-128cm 7m 131m !-+.-,#,2#1m "30,2#m *m 1#%3,"m 3#00m 3,"'*Ym 6'12#,m 40'-1m %#,2#1m */3'*,2#1m !-+-m #*m +#2'*+#2,-m 13*$2-m ^_Zm 2'*m #2,-m 3*$-,2-m ^_Zm 7m *m ,'20-1-%3,'"',m /3#m $#!2,m *m Ym 12-1m %#,2#1m 1-,m #$'!'#,2#1m +329%#,-1m 7m "#m $9!'*m 32'*'8!'A,Ym 1m .-0m #**-m /3#m 1-,m & '23*+#,2#m 31"-1m #,m .*,21Zm #,m #1.#!'*m #*m Ym *m m */3'*m *1m %3,',1Zm &!'#,"-m /3#m m #*m #+.0#(+'#,2-m 1#m !-,m *m 2'+',m 7m ,-m !-,m *m !'2-1',m 7m .-0m *-m 2,2-m .0-4-!m 20,1'!'-,#1m "#*m 2'.-m ijim ^#%Zm GONJ_m ^'%30mGYI_Ym m m m m (&30 TBMD[m$#!2-m"#*mmm,'4#*m+-*#!3*0Ym1m%3,',1m7m*1m2'+',1m1#m+#2'*,m7m#1#m!+ '-m/3>+'!-m &!#m /3#m 1#m !-+.-02#,m !-+-m 3,m "#,',m 7m 3,m !'2-1',m 0#1.#!2'4+#,2#m 7m #,m !-,1#!3#,!'m !-+.*#+#,2,m !-,m 1#1m "'12',21m m *1m /3#m "# #0>,m !-+.*#+#,201#m ^$3#,2#[m &22.[ii555Y3!+Y#1i',$-i%#,#2'!i%03.-"i32!'-,i+32!'-,Y&2+_YT m HI (.,)/#9( Mutagénesis inducida m _mmm -1m %#,2#1m ',2#0!*,2#1m 1-,m +-*<!3*1m /3#m 2'#,#,m ,*-%>m !-,m *-1m ,3!*#A2'"-1m 7m .-0m *-m 2,2-Zm 1-,m !.!#1m "#m "#1*'801#m #,20#m <12-1m #m ',2#0!*01#m #,m *m "- *#m &<*'!#m &!'#,"-m/3#m*m.-*'+#01m1#m#/3'4-/3#m7m@"m-20m 1#m.0-"3!'#,"-m"#*#!'-,#1m -m!-00'+'#,2-1m"#m*#!230Ym,m#(#+.*-m"#m#12-1m%#,2#1m1-,m*m.0-$*4',m7m*m,0,(m "#m!0'"',Zm1>m!-+-m#*m 0-+30-m"#m#2'"'-m^* #021m7m!-*YZmHFFL_Ym T BMDMDMCTTT T _mmm 1m 0"'!'-,#1m #*#!20-+%,<2'!1m #129,m $-0+"1m .-0m *m !-+ ',!'A,m "#m !+.-1m +%,<2'!-1m7m#*<!20'!-1m7m1#m.0-.%,mm204<1m"#*m#1.!'-m20,1.-02,"-m#,#0%>Ymm 0"'!'A,m#*#!20-+%,<2'!Zm!37m*-,%'23"m"#m-,"m#129m#,20#m*-1mJFFm7m*-1mGKm,+m1#m "#,-+',mm^3*204'-*#2_Ymm*-,%'23"m"#m-,"m"#*mm!#0!,-m#129m#,20#m*-1mHFFj JFFm,+Ym12m#1m*m+'1+m*-,%'23"m"#m-,"m/3#m 1-0 #m#*mZm!-,m3,mA.2'+-m#,m HKJm ,+m /3#m #1m *m 1-0!'A,m +96'+Ym 12m !0!2#0>12'!m &!#m /3#m #*m m .3#"m .0-4-!0m *#1'-,#1m #,m #*m Ym 1m +32!'-,#1m .0-"3!'"1m +91m !-+B,+#,2#m 1-,m ">+#0-1m "#m '+',1m 7m #121m "3.*'!!'-,#1m .0-4-!,m /3#m #,m *m 0#.*'!!'A,m *m m .-*'+#01m',1#02#m3,m,3!*#A2'"-m',!-00#!2-m#,m#1m.-1'!'A,Ymm _mmm 1m 0"'!'-,#1m '-,'8,2#1m 1-,m /3#**1m 0"'!'-,#1m !.!#1m "#m '-,'80m *m +2#0'Zm #6207#,"-m *-1m #*#!20-,#1m "#m 131m #12"-1m #*#!20A,'!-1m /3#m *#1m +,2#,>,m *'%"-1m *m 92-+-Ym ,20#m *1m .-2#,2#1m #1.#!'#1m /3>+'!1m $-0+"1m .-0m *m 0"'!'A,m '-,'8,2#m 1#m #,!3#,20,m*-1m0"'!*#1m*' 0#1Zm1'#,"-m#*m+91m'+.-02,2#m#*m0"'!*m&'"0-6'*-m^j_Zm /3#m 0#!!'-,m !-,m +!0-+-*<!3*1Zm !-+-m #*m Zm 7m *1m ',!2'4m .0-"3!'#,"-m 0-2301m /3#m .3#"#,m "0m *3%0m m !+ '-1m #1203!230*#1m '+.-02,2#1Zm !-+-m 1-,m *1mm +32!'-,#1m!0-+-1A+'!1m^&'0*#7ZmGOOH_Ym m0"'!'A,m'-,'8,2#m&m1'"-m+.*'+#,2#m32'*'8"m.0m',"3!'0m+32!'-,#1m#,m*m +#(-0m %#,<2'!m ^03%%#+,,m 7m !-*YZm GOOL\m #!!&','m 7m !-*YZm GOON\m &')8-,-m 7m !-*YZm GOONm 7m HFFG_Ym ,m .*,21m 1#m &m - 1#04"-m /3#m #*m 31-m "#m 0"'!'-,#1m '-,'8,2#1m .0-"3!#m +7-0+#,2#m "#*#!'-,#1m 7m +-"'$'!!'-,#1m !0-+-1A+'!1Ym 1m 0"'!'-,#1m '-,'8,2#1m .3#"#,m .0-4#,'0m "#m 1312,!'1m /3#m #+'2#,m #121m 0"'!'-,#1m "#m $-0+m #1.-,29,#m-m '#,m"#m%#,#0"-0#1m02'$'!'*#1m!-+-m.-0m#(#+.*-m*-1m%#,#0"-0#1m"#m 07-1mm-m*-1m!#*#0"-0#1m"#m.02>!3*1Ym HJ /.!6(-#-O#(/#O (.,)/#9(O j"'!'-,#1m++m7m07-1j[m1m0"'!'-,#1m!-,m07-1m%++j^v_m7m07-1j m .0-"3!#,m "#*#!'-,#1m 7m -201m +32!'-,#1m !0-+A+'!1Zm 3,/3#m 1A*-m *%3,1m "#m#**1m&,m1'"-m!0!2#0'8"1mm,'4#*m+-*#!3*0m^..#,&#'+#0m7m!-*YZmGOOG\m &'0*#7m7m!-*YZmGOOH\m+ 0m7m!-*YZmGOOJ_Ym-1m07-1m%++j^v_m7m*-1m07-1jm &,m1'"-m31"-1m.0m.0-"3!'0m+32,2#1m#,m,#)*-#-m^<"#'m7m-,!8ZmGOOH_m 7m#,m00-8m^,8--0m7m&##+ZmHFFI_Ym3m7m!-* -0"-0#1m^HFFK_m310-,m"-1m "-1'1m "'$#0#,2#1m "#m 07-1m %++j^v_m ^HKFm 7m KFFm 7_m .0m .0-"3!'0m 3,m !-*#!!'A,m "#m +32,2#1m #,m LJm ^40'#""m #(#m "#*m 00-8_m #,m *-1m !3*#1m +'"'#0-,m #*m 2+@-m "#m *1m "#*#!'-,#1m ^#,m '*- 1#1_m !-+.0- ,"-m *1m *2#0!'-,#1m!0-+-1A+'!1m^3m7m!-*YZmHFFK_Ym m j#320-,#1m 09.'"-1[m *m +<2-"-m "#m %#,<2'!m ',4#01m 1"-m #,m #*m -.O (/.,)(m ^',"3!2-0m"#m"#*#!'-,#1_m&m1'"-m"#100-**"-m.0m'"#,2'$'!0m7m'1*0m%#,#1m"#m ',2#0<1m #,m .*,21m ^'m 7m !-*YZm HFFG\m 'm 7m &,%Zm HFFH\m 3m 7m !-*YZm HFFK_Ym #m !3#0"-m!-,m'm7m!-*Ym^HFFG_Zm#12#m+<2-"-m.0-"3!#m"#*#!'-,#1m!-,m#$'!'#,!'m7m 2+ '<,m 1#m .3#"#,m .0-"3!'0m *>,#1m +32,2#1m !-,m 3,m !- #0230m "#m +32!'A,m +91m #$'!'#,2#m /3#m !-,m *m +32%<,#1'1m ',1#0!'-,*m /3#m -$0#!#m *m2#!,-*-%>m "#*m jYm 12#m +<2-"-m &m 1'"-m 31"-m #,m 00-8Zm .0-"3!'#,"-m NZFFFm *>,#1m +32,2#1m#,m*m40'#""m#(#mLJm^3m7m!-*YZmHFFK_Ymm m j-,#1m!#*#0"-1[m1,"-m'-,#1m"#m!0 A,m'-,'8"-1Zm1#m&,m!-,1#%3'"-m'1*0m ,3#4-1m+32,2#1m#,m,#)*-#-m^-.FO ,&;FO/0#;FO-/0;FO..;AZm7m..;B_m^,)m7m!-*YZm GOOM\m 1#m 7m !-*YZm HFFF\m )+-2-m 7m !-*YZm HFFI\m &')8-,-m 7m !-*YZm HFFI_Ym ,*'8,"-m *m 1#!3#,!'m ,3!*#-2>"'!m "#m *-1m +32,2#1m 1#m "#1!3 0'Am /3#m *1m +32!'-,#1m .0-"3!'"1m #0,m ',4#01'-,#1Zm 20,1*-!!'-,#1Zm 7m .#/3#@1m "#*#!'-,#1m ^&')8-,-m 7m !-*YZm GOONZm HFFIZm )+-2-m 7m !-*YZm HFFI_Ym 123"',"-m !-,m"#2**#m*m$0#!3#,!'m"#m#12-1m!+ '-1Zm1#m- 234-m/3#m*m$0#!3#,!'m"#m*1m "#*#!'-,#1m #0m "#m LYGm Rm GFjKZm $0#!3#,!'m !-+.0 *#m m *m ',"3!'"m .-0m *-1m ,#320-,#1m 09.'"-1m ^'m 7m !-*YZm HFFG_Ym 12-1m 0#13*2"-1m ',"'!0-,m /3#m *m +32%<,#1'1m+#"',2#m'-,#1m!#*#0"-1m.-">m1#0m31"m2,2-m.0m*m%#,<2'!m "'0#!2m!-+-m.0m*m%#,<2'!m',4#01m"#m.*,21Ymm m T T T T T HK (.,)/#9( Mutagénesis inducida BMDMDMDTTTTT m _mm -1m #*#+#,2-1m 20,1.-,' *#1m 2'#,#,m *m !.!'""m "#m "#1.*801#m .-0m #*m %#,-+m #m ',2#%001#m#,m3,m0#%'A,Ym'm*m0#%'A,m"-,"#m1#m',2#%0,m#1m3,m%#,Zm<12#m.3#"#m.#0"#0m 13m $3,!'-,*'""m "# '"-m m /3#m 1#m *2#0m 13m 1#!3#,!'Ym -1m 20,1.-1-,#1m 1-,m +-*<!3*1m "#m m !-,m !.!'""m +A4'*Ym '#,#,m *m !.!'""m "#m 1*20m "#m 3,m .-1'!'A,m m -20m "#*m %#,-+Ym -1m 20,1.-1-,#1m 1#m &,m !*1'$'!"-m #,m $3,!'A,m "#m 13m +#!,'1+-m "#m 20,1.-1'!'A,Zm "#.#,"'#,"-m "#m 1'm #12#m .0-!#1-m 1#m "m !-,m 3,m .1-m ',2#0+#"'-m"#m20,1!0'.!'A,m^0#20-20,1.-1-,#1_m-m1'm1'+.*#+#,2#m1#m"#1.0#,"#,m7m1#m !-.*,m#,m0#%'-,#1m"'4#011m"#*m%#,-+mI20,1.-1-,#1m"#mJEmm32'*'8!'A,m"#m 20,1.-1-,#1m !-+-m +<2-"-m "#m +32%<,#1'1m ',1#0!'-,*m &m 1'"-m 31"m !-+-m 2#!,-*-%>m"#m%#,<2'!m',4#01m^'0-!&')m7m!-*YZmHFFJ\m!027m7m!-*YZmHFFK_Ymm m _mjm^mm_m !,).,#/'O./' #(-O#1m3,m !2#0'm/3#m.3#"#m',$#!20mm+91m"#mIIFm%<,#0-1m"#m "'!-2'*#"A,#1m ^8/3'#0"-m 7m !-*YZm HFFG_Ym m !2#0'm .3#"#m ',$#!20m m 204<1m "#m 3,m &#0'"m -m 3,m ',!'1'A,m 20,1$'0'#,"-m #,m #**m #*m .*91+'"-m #m ^',"3!2-0m "#m 23+-0#1_m 7m .0-4-!9,"-*#m m *m .*,2m 3,m 23+-0m !**-1-m "#,-+',"-m b23+-0m "#m *m !-0-,cYm *m .*91+'"-m#m+'"#m#,20#mGKFjHFFm m"#m*1m!3*#1mHFjHIm1#m',2#%0,m*#2-0'+#,2#m#,m 40'-1m *3%0#1m "#*m %#,-+m &3<1.#"Ym m #12#m m 1#m *#m "#,-+',m jm ^m 20,1$#0'"-_m^8/3'#0"-m7m!-*YZmHFFG_Em12m.0-.'#""m"#m',2#%0!'A,m#,m#*m%#,-+m1#m &m31"-m.0m#*m'1*+'#,2-m"#m%#,#1m#,m.*,21Ym*mjm',20-"3!#m+32!'-,#1m*m 80m **#%,"-m m ',!2'40m *m $3,!'A,m "#m 3,m %#,Ym #"',2#m #12m 2#!,-*-%>m #1m .-1' *#m '1*0m#*m%#,m/3#m#1m0#1.-,1 *#m"#m*m$*2m"#m$3,!'A,m!-,m1-,"1m#1.#!>$'!1m.0m#*m jm7m*m+'1+-m2'#+.-Zm0#*!'-,0*-m!-,m3,m$#,-2'.-m+32,2#m^8/3'#0"-m7m!-*YZm HFFG_Em12m2#!,-*-%>m"#m+32%<,#1'1m',1#0!'-,*m1#m&m32'*'8"-m2,2-m#,m,#)*-#-O ."&#(Zm !-+-m #,m 00-8m ^&22.[ii1'%,*Y#"3i!%'j ',i2",#6.0#11m 7m &22.[ii1'%,*Y1*)Y#"3i!%'j ',i'!#_m 7m #,m +3!&1m -201m #1.#!'#1m ^,m 7m !-*YZm HFFI_Zm #,20#m #**1m #,m 1,">Zm .0m - 2#,#0m 0#1'12#,!'1m m 4'031m !-+-m #*m 4'031m "#*m +-1'!-m +0'**-m"#*m!* !>,m^_m^3m7m!-*YZmHFGG_Ymm _mm -1m 4'031m 1-,m +-*<!3*1m ',$#!2'41m /3#m .3#"#,m !*1'$'!01#m #,m $3,!'A,m "#m *m ,230*#8m "#m 13m +2#0'*m %#,<2'!-m ^+-,-m -m '!"#,m "#m m -m m 1#%B,m *m !*1'$'!!'A,m"#m*2'+-0#m^*2'+-0#m7m+-0#ZmGOMG__Ym-1m4'031m',$#!2,mm*1m.*,21m m 204<1m "#m .*%1m ^',1#!2-1_m 3m &-,%-1Ym m 32'*'8!'A,m "#m 4'031m #,m .*,21m !-+-m HL /.!6(-#-O#(/#O (.,)/#9(O 4#!2-0#1m .3#"#m -$0#!#0m %0,"#1m 4#,2(1Ym #m +3*2'.*'!,m 09.'"+#,2#m 7m .3#"#,m .0-"3!'0m3,m%0,m,B+#0-m"#m!-.'1m"#*m20,1%<,m^',1#02"-m.0#4'+#,2#m#,m#*m4'031_m *!,8,"-m 4*-0#1m +96'+-1m #,m 3,m -m "-1m 1#+,1m "#1.3<1m "#m *m ',$#!!'A,m ^8/3'#0"-m 7m !-*YZm HFFG_Ym 3,/3#m 1#m &,m "#1!3 '#02-m 40'-1m 4'031m #,m .*,21m /3#m .3#"#,m 3101#m !-+-m 4#!2-0#1m ^.-0m #(#+.*-m #*m 4'031m "#*m (1.#"-m "#*m 2 !-m ^_m ^%3"#*-j-+#0-m 7m !-*YZm HFFN__m 13m 32'*'8!'A,m ,-m #1m +37m $0#!3#,2#Ym *m +7-0m .0- *#+m /3#m .0#1#,2,m *-1m 4'031m #,m .*,21m #1m /3#m 1'm #*m %#,m ',1#02"-m 13.#0m *m '*- 1#Zm13m',#12 '*'""m#1m+37m*2m7m*m.*,2m*-m#*'+',m^8/3'#0"-m7m!-*YZmHFFG_Zm ^0'%&2m7m-721ZmGOON_Ym 0!'1m *m +#!,'1+-m ',$#!2'4-m "#m *-1m 4'031m !-+ ',"-m !-,m *-1m +#!,'1+-1m "#m "#$#,1m "#m *1m .*,21m 1#m &m .-"'"-m "#100-**0m *m 2<!,'!m "#,-+',"m '*#,!'+'#,2-m<,'!-m,"3!'"-m.-0m'031m^_m^3m7m!-*YZmHFFI_Ym3,"-m#*m4'031m ',$#!2m m *m .*,2m <12m "#1#,!"#,m 3,m +#!,'1+-m "#m "#$#,1m 1"m #,m *m ',2#0!!'A,m !-,m #*m +m "#*m 4'031m 7m #,m !-,1#!3#,!'m 1#m *-/3#m 13m 20,1!0'.!'A,Ym ',m #+ 0%-Zm 1'm 1#m 31m #*m 4'031m !-+-m 4#!2-0m ',1#029,"-*#m 3,m %#,m "#m *m .*,2m &-1.#""-0m#*m.0-!#1-m'09m"'0'%'"-m!-,20m*-1m+m"#*m+'1+-m%#,m1'*#,!',"-m1>m 13m#6.0#1'A,m^3m7m!-*YZmHFFK_Ymm _mmm Una de las recientes tecnologías descritas de mutagénesis dirigida en plantas es la denominada tecnología TALENs (Transcription Activator-Like Effector Nucleases). Existen patógenos bacterianos del género Xanthomonas que infectan a una amplia gama de especies y que durante la infección, proporcionan a las células de la planta una serie de proteínas conocidas como Transcription Activator-Like Effectors (Boch y Bonas, 2010). Estas proteinas se unen a promotores de genes diana de la planta y de este modo modifican el transcriptoma de la planta huésped. Para unirse al ADN de la planta, TALE contiene un dominio de unión compuesto por varias repeticiones de monómeros de 34 aminoácidos cada uno de los cuales sólo dos residuos, que están localizados en las posiciones 12 y 13, son hipervariables. Cada motivo hipervariable TALE reconoce un par de bases en una secuencia de ADN. TALENs se ha creado mediante la fusión de un dominio de unión (TALE) con una nucleasa FokI. De este modo el complejo puede reconocer una secuencia concreta y producir un corte de doble cadena en un sitio específico para inducir mutagénesis dirigida, como por ejemplo la inserción de un fragmento exógeno de doble cadena induciendo a la represión o activación del gen dependiendo de la función del HM (.,)/#9( Mutagénesis inducida dominio donde se ha localizado la inserción de TALENs. Esta tecnología de mutagenesis dirigida ya se ha usado con éxito en varias especies como por ejemplo en Arabidopsis thaliana (Cermak y col., 2011). m HN O (.,)/#9(O m m BMETT m BMEMBTT *m m ^,!.#(!O (/O )&O -#)(-O O ()'-_m #1m 3,m 2<!,'!m "#m %#,<2'!m ',4#01m/3#m!-+ ',m*m%#,#0!'A,m"#m+32!'-,#1m.3,2'$-0+#1m^-m1_m',"3!'"1mm 204<1m "#m 3,m %#,2#m +329%#,-m !-,m 3,m #$'!'#,2#m 2<!,'!m "#m 0120#-m +-*#!3*0Zm /3#m .#0+'2#m '"#,2'$'!0m *-1m .-*'+-0$'1+-1m m ,'4#*m "#m 1#!3#,!'m ,3!*#-2>"'!m #,m "'4#011m #1.#!'#1m 4#%#2*#1m ^!**3+m 7m !-*YZm HFFFm Zm _Ym 0!'1m m #12m 2<!,'!m #1m .-1' *#m *-!*'80Zm#,m3,m.- *!'A,m!-,12'23'"m.-0m+'*#1m"#m',"'4'"3-1Zm3,m1#0'#m*<*'!m"#m +32!'-,#1m.3,2'$-0+#1m',"3!'"1m#,m%#,#1m"#m',2#0<1m^'**m7m!-*YZmHFFI_Ym m 2<!,'!m "#*m m $3#m 32'*'8"m .-0m .0'+#0m 4#8m .-0m !**3+m #,m *m .*,2m +-"#*-m ,#)*-#-O ."&#(m ^!**3+m 7m !-*YZm HFFF_m 7m "#1"#m #,2-,!#1m &m 1'"-m 3,m 2<!,'!m32'*'8"m!-,m<6'2-m#,m40'-1m-0%,'1+-1m7m1#,m4#%#2*#1m^20'%-m"30-m^*"#m 7m !-*YZm HFFJ_\m !# "m ^*+=m 7m !-*YZm HFFN_\m 00-8m ^'**m 7m !-*YZm HFFM_\m +>8m ^'**m 7m !-*YZm HFFJ_\m1-(m^--.#0m7m!-*YZmHFFN_\m%3'1,2#m^*+'1m7m!-*YZmHFFN_\m+#*A,m^&+,'j 0"1m 7m !-*Zm HFGF\m -,8*#8j-m 7m !-*YZm HFGG_\m )./-O $*)(#/-m ^#007m 7m !-*YZm HFFI\m '*!&0'12m7m3%&,ZmHFFK__m-m,'+*#1m^.#8j8# 0m^'#,&-*"1m7m!-*YZmHFFI_\m,)-)*"#&O '&()!-.,O ^',)*#0m 7m !-*YZm HFFK_\m (),"#.#-O &!(-m ^'*!&0'12m 7m !-*YZm HFFL__Zm ',"#.#,"'#,2#+#,2#m"#m*1m"'+#,1'-,#1m"#m*-1m%#,-+1Ymm 12m 2<!,'!m 2'#,#m *%3,1m !0!2#0>12'!1m /3#m *m &!#,m .#!3*'0m 7m 4#,2(-1Ym #12!0#+-1m 20#1m .-0m 13m 0#*#4,!'Ym m .0'+#0Zm #1m /3#m ,-m 1#m 0#/3'#0#m #*m 31-m "#m 20,1$-0+!'A,m%#,<2'!m7m.-0m*-m2,2-m*-1m+32,2#1m- 2#,'"-1m,-m1-,m20,1%<,'!-1Ym 12m !0!2#0>12'!m #1m 3,m 4#,2(m .3#12-m /3#m *-1m 20,1%<,'!-1m ,-m #129,m !#.2"-1m 1-!'*+#,2#m #,m 30-.m 7m #12-m .#0(3"'!m *m !-+#0!'*'8!'A,m "#*m .0-"3!2-m "#m -0>%#,m 20,1%<,'!-Ym m 1#%3,"m #1m /3#m #1m 3,m 2<!,'!m /3#m .3#"#m 1#0m 32-+2'8"m 7m -.2'+'8"m .#0+'2'#,"-m ,*'80m 3,m %0,m ,B+#0-m "#m +3#1201m #,m 3,m 2'#+.-m +>,'+-Ym ',*+#,2#Zm %0!'1m m #12#m +<2-"-m 1#m .3#"#,m - 2#,#0m ,-m 1A*-m +32!'-,#1m 1',m1#,2'"-Zm1',-m2+ '<,m+32!'-,#1m"#*m2'.-m1312'232'4-m*1m!3*#1m.3#"#,m$#!20mm *m$3,!'A,m"#*m%#,m1',m**#%0mm',!2'40*-Zm#1m"#!'0Zm!0#,"-m1#0'#1m*<*'!1Ym #1"#m 3,m .3,2-m "#m 4'12m 2#A0'!-Zm *m 2<!,'!m m !-,1'12#m #,m ',"'4'"3*'80m *1m 40',2#1m *<*'!1m /3#m !-,2'#,#,m 3,m +32!'A,m 1'%,'$'!2'4m ^.-0m #(#+.*-Zm /3#m .0-"38!,m !+ '-1m "#m +',-9!'"-_m +#"',2#m 3,m 0120#-m +-*#!3*0Ym "#+91Zm 1#m HO (.,)/#9(O O .3#"#,m1#*#!!'-,0m,3#4-1m%#,-2'.-1m/3#m.0-4-!,m$#,-2'.-1m/3#m.3#"#,m1#0mB2'*#1m m,'4#*m!-+#0!'*Ym*mm#1m3,m2<!,'!m.*'! *#mm2-"-1m*-1m-0%,'1+-1m7m/3#m 13m#$'!'#,!'m,-m"#.#,"#m"#*m2+@-m"#*m%#,-+Zm,'m"#*m1'12#+m0#.0-"3!2'4-Zm,'m"#*m !'!*-m '-*A%'!-m ^'*!&0'12m 7m 3%&,Zm HFFK_Ym 20m 4#,2(m #1m /3#m *1m +32!'-,#1m 1#m .0-"3!#,m m 204<1m "#m +32%<,#1'1m /3>+'!m 7m .-0m *-m 2,2-Zm 1-,m +32!'-,#1m '00#4#01' *#1m 7m "'120' 3'"1m *#2-0'+#,2#m m *-m *0%-m "#m 2-"-m #*m %#,-+Ym 1m .- *!'-,#1m'"#*#1m1-,m/3#**1m#,m*1m/3#m1#m.3#"#,m'"#,2'$'!0m+32,2#1m.0m!"m %#,m "',m ,*'8"-Ym "#+91Zm +#"',2#m #12m 2<!,'!m 1#m .3#"#,m ,*'80m 2+ '<,m "'$#0#,!'1m %#,-2>.'!1m ,230*#1m #,20#m 40'#""#1m "#m 3,m +'1+m #1.#!'#m *-m /3#m 1#m "#,-+',Zm +91m #1.#!>$'!+#,2#Zm !-m ^"#m ).3*m _m ^-+'m 7m !-*YZm HFFJ_Ym T BMEMCTTTTT m 2<!,'!m "#*m m 1#m "'4'"#m #,m 20#1m $1#1[m G_m 0-"3!'0m *m .- *!'A,m +32%#,'8"ZmH_m#100-**0m*m.*2$-0+[m#620!!'A,m7m.0#.0!'A,m"#*mm.0m #*m0120#-Zm7m I_m,*'80m7m"#2#!20m*-1m+32,2#1m.0m*-1m%#,#1m"#m',2#0<1m#,m*m.- *!'A,Ym ,m .0'+#0m *3%0m 1#m "#100-**m *m .- *!'A,m +32,"-m *1m 1#+'**1m Fm 7m !0#!'#,"-m *m %#,#0!'A,m Gm ^'%30m GYJ_Ym -12#0'-0+#,2#Zm m 204<1m "#m *m 32-$#!3,"!'A,m "#m *-1m ',"'4'"3-1m Gm 1#m - 2'#,#m *m %#,#0!'A,m HYm 1m 1#+'**1m "#m *m %#,#0!'A,m Hm 1#m 0#!-%#,m7m1#m*+!#,,m"#m+-"-m/3#m3,m4#8m'"#,2'$'!"1m*1m$+'*'1m+32,2#1m1#m .3#",m4-*4#0mm.*,20m',"'4'"3-1mHm.0m!-,$'0+0m#*m$#,-2'.-m7m*m1#%0#%!'A,m "#m *m +32!'A,Ym ,m 4#8m - 2#,'"m *m %#,#0!'A,m Hm 2+ '<,m 1#m .0-!#"#m m *m #620!!'A,m "#*m +2#0'*m %#,<2'!-Ym 12#m +2#0'*m %#,<2'!-m #1m #*m 0#13*2"-m "#m *m #620!!'A,m"#mm"#m*m+#8!*m"#m*1m+3#1201m"#m&-(m"#m"'#8m',"'4'"3-1m"#m!"m $+'*'m HYm #1.3<1m "#m #620#0m #*m m "#m 2-"1m *1m $+'*'1m /3#m !-+.-,#,m *m .- *!'A,Zm1#m-0%,'8m#,m.*!1m+#8!*,"-m#*mm"#m!"m!320-mm-!&-m$+'*'1m .0m.-"#0m%'*'80m#*m.0-!#1-m"#m"#2#!!'A,m"#m+32,2#1m^+#8!*m"#m1m-m.--*1_Ym 0m #*m "#100-**-m "#m *%3,1m .- *!'-,#1m #12#m .0'+#0m .1-m #,m #*m /3#m 1#m - 2'#,#m #*m m"#m*m.- *!'A,m&m40'"-m*'%#0+#,2#Ym*%3,-1m32-0#1m&,m#620>"-m#*mm "#m 2,m 1-*-m 3,m .*,2m "#m *m %#,#0!'A,m Hm 7m ,-m "#m *m +#8!*m "#m "'#8m ',"'4'"3-1Zm 0#"3!'#,"-m 1>m !-,1'"#0 *#+#,2#m #*m 2'#+.-m "#m *m .0#.0!'A,m "#m *m .- *!'A,Zm 3,/3#m #,m #12#m !1-m 1#m 13#*#m 32-$#!3,"0m #*m ',"'4'"3-m Hm .0m .#0.#230m m *m +32!'A,m#,m*m1'%3'#,2#m%#,#0!'A,Ym IF O (.,)/#9(O m !-,2',3!'A,m 1#m ','!'m #*m .0-!#1-m "#m "#2#!!'A,m "#m +32,2#1m #,m %#,#1m "#m ',2#0<1Ym 0m #**-Zm 1#m "'1#@,m !# "-0#1m "#m +-"-m /3#m +.*'$'/3#,m *1m 8-,1m "#*m %#,m /3#m 1#m /3'#0#,m,*'80Ym#"',2#m#*m"'1#@-m"#m!# "-0#1m#1.#!>$'!-1m1#m.3#"#m.0-!#"#0mm*m +.*'$'!!'A,m "#*m %#,m ^-m "#m 3,m 0#%'A,m "#*m %#,_m +#"',2#m Ym m m 1#m 0#*'8m 1- 0#m*m+#8!*m"#m1m+#,!'-,"m,2#0'-0+#,2#Zm.-0m*-m2,2-Zm+.*'$'!09m2-"-1m *-1m*#*-1m/3#m1#m#,!3#,20#,m#,m#1#m+#8!*m^2,2-m#*m*#*-m1'*4#120#m!-+-m#*m+32"-_Ym ,m4#8m"#1,230*'8"-m#*m.0-"3!2-m"#m*mm1#m.0-!#"#mm*m0#,230*'8!'A,Ym,m #*m !1-m "#m *m 0#,230*'8!'A,m #,20#m 3,m !"#,m +32"m !-,m 3,m 1'*4#120#m *m !-+.*#+#,2!'A,m ,-m 1#09m 2-2*m 7m .-0m *-m 2,2-m 1#m .0-"3!'09m 3,m &#2#0-"B.*#6m #,m #*m ,3!*#A2'"-m +32"-Ym -12#0'-0+#,2#Zm 3,m #,"-,3!*#1m /3#m "'%'#0#m #6!*31'4+#,2#m &#2#0-"B.*#6m ^&O _m 1#09m *m 0#1.-,1 *#m "#m !-020m *1m !"#,1m "-,"#m &7m 3,m +32!'A,Ym #1.3<1m 1#m 4'13*'8,m *-1m $0%+#,2-1m "'%#0'"-1m #,m 3,m jm JIFFYm m "#2#!!'A,m "#m *1m +32!'-,#1m -m 1m .3#"#m &!#01#m +#"',2#m -20-1m +<2-"-1m /3#m 1#m !-+#,209,m .-12#0'-0+#,2#Zm !-+-m .-0m #(#+.*-Zm #*m m ^#!"O -)&/.#)(O &.#(!_Zm 3,/3#m#*m+<2-"-m+91m& '23*m#1m#*m31-m"#*mlmJIFFZm32'*'8"-m#,m#12#m20 (-Ym 0!'1mm#12m2#!,-*-%>m1#m.3#"#,m4'13*'80m"-1m!,*#1m"'12',2-1m#,m*-1m!3*#1m1#m "#2#!2,m*-1m$0%+#,2-1m+.*'$'!"-1m"#1"#m!"m!# "-0mKam-mIam"#m*m!"#,m&12m #*m.3,2-m"#m"'%#12'A,Ym#m#12#m+-"-Zm1#m.3#"#m!-,$'0+0m*m+32!'A,m.3#12-m/3#m*m 13+m "#*m 2+@-m "#m *-1m $0%+#,2-1m "'%#0'"-1m #,m !"m !,*m "# #m !-',!'"'0m !-,m *m 2-2*'""m "#*m 2+@-m "#*m $0%+#,2-m +.*'$'!"-m 1',m "'%#0'0m ^*m #6.*'!!'A,m "#m *m 4'13*'8!'A,m "#m *-1m $0%+#,2-1m "'%#0'"-1m #,m #*m jm #129m "#2**"m #,m *m '%30m GYK_Ym IG (.,)/#9(O O T (&30 T BME[m 0-2-!-*-m #+.*#"-m .0m #*m +<2-"-m "#m Ym ,m 4#8m +32"1m *1m 1#+'**1m ^F_m !-,m #*m +329%#,-mZm1#m!0#!#m*m%#,#0!'A,mGYm#"',2#m*m32-$#!3,"!'A,m"#m#12m%#,#0!'A,m1#m- 2'#,#m*m %#,#0!'A,m HYm #m !"m $+'*'m Hm 1#m !0#!#,m GFm ',"'4'"3-1m 7m 1#m *#1m 2-+m 3,m +3#120m "#m &-(Ym -12#0'-0+#,2#Zm1#m#620#m#*mm"#m#1m+#8!*m7m"#m#12#m+-"-m1#m- 2'#,#m#*mm"#m!"m$+'*'mHYm#m *m %#,#0!'A,m Hm 2+ '<,m 1#m *+!#,,m *1m 1#+'**1m .0m #6.#0'+#,2-1m $3230-1Ym -1m 1m "#m 2-"1m *1m $+'*'1m1#m-0%,'8,m#,m.*!1m+#8!*9,"-*1m"#m!320-m#,m!320-Zm#,m,3#120-m!1-Y0m*m"#2#!!'A,m"#m*-1m +32,2#1Zm.0'+#0-m1#m+.*'$'!m#*m%#,m"#m',2#0<1Ym#1.3<1m1#m"#1,230*'8,m*1m!"#,1m7m"#m#12#m+-"-m1#m .0-4-!,m*-1m&#2#0-"B.*#6m/3#m"'%#0'09m*m#,"-,3!*#1m&EO',*+#,2#Zm*m"#2#!!'A,m"#m*-1m$0%+#,2-1m "#m"'%#12'A,m1#m0#*'8m31,"-m#*mjmJIFFYm m BMEMCMBTTTTTT 1m.*,21m1-,m-0%,'1+-1m'"#*#1m.0m+32%#,'80m7m/3#m2'#,#,m*m!.!'""m"#m +,2#,#0m*m-0%,'1+-m#,m3,m#12"-m*2#,2#m!-,m*m1#+'**Ym*m+329%#,-m'"#*m.0m 310m #,m #*m +<2-"-m "#m m #1m /3<*m /3#m ',"3!#m +32!'-,#1m *#2-0'+#,2#m IH T O (.,)/#9(O 0!,"-m 0#%'-,#1m !-"'$'!,2#1m 7m #,m 3,m *2m $0#!3#,!'m 7m 1#,m .3,23*#1Zm .#/3#@1m "#*#!'-,#1m -m ',1#0!'-,#1Ym *m +329%#,-m /3>+'!-m m ^2'*m #2,-m 3*$-,2-_m %#,#0m 1m ^20,1'!'-,#1m [j[m ^0##,#m 7m !-*YZm HFFIZm *"#m 7m !-*YZm HFFK__m 7m 1#m .3#"#m .*'!0Zm -.2'+'8,"-m *m "-1'1m #,m !"m #1.#!'#Zm .0m .0-"3!'0m +32!'-,#1m 1',m .0-"3!'0m *#2*'""m "#m *1m 1#+'**1m -m "#m *1m .*,21m ^0##,#m 7m !-*YZm HFFIZm --0,,##$m 7m !-*YZm GONH_Ym *m .0-!#"'+'#,2-m & '23*m 31"-m &12m &-0m .0m .0-"3!'0m .*2$-0+1m "#m m &m 1'"-m ',20-"3!'0m *1m 1#+'**1m #,m 3,m 1-*3!'A,m !-,m#*m+329%#,-m"'*3'"-m"30,2#m.0-6'+"+#,2#mGFjHJm&-01m7m#,m-1!30'""Zm1>m 1#m !-,1'%3#m +320m *1m !<*3*1m "#*m #+ 0'A,m /3#m +91m 20"#m .0-"3!'09,m *-1m 2#('"-1m 0#.0-"3!2'4-1Ym ,m *m +7-0>m "#m *-1m !1-1m *-1m ',"'4'"3-1m "#m *m %#,#0!'A,m Gm 2#,"09,m*m+32!'A,m#,m&#2#0-!'%-1'1m7m.0- *#+#,2#m1A*-m#,m3,m.02#m"#m*m.*,2Ym 0m 1#%300m *m .0- '*'""m "#m #,!-,200m *m +32!'A,m #,m &-+-!'%-1'1m &!#m $*2m 32-$#!3,"0m *m %#,#0!'A,m Gm 7m - 2#,#0m *m %#,#0!'A,m HYm #m #12#m +-"-m *m .0- '*'""m"#m#,!-,200m3,m',"'4'"3-m&-+-!'%-2-m1'%3#m*m.0-.-0!'A,m"#m&#0#,!'m +#,"#*',m G[H[Gm ^#,')-$$m 7m -+'Zm HFFI_Ym + '<,m #,m *%3,1m #1.#!'#1m !-+-m #,m +>8m1#m&m.*'!"-m#*m+329%#,-m"'0#!2+#,2#m#,m#*m.-*#,m.0m*3#%-m',20-"3!'0*-m#,m *m $*-0m $#+#,',m 1'*4#120#m "#m *m +'1+m 40'#""Ym 1m 1#+'**1m "#m *1m +8-0!1m 0#13*2,2#1m 1#m %#0+',,m .0m - 2#,#0m *m %#,#0!'A,m GYm -12#0'-0+#,2#m +#"',2#m 32-$#!3,"!'A,m1#m- 2'#,#m*mHm^'**m7m!-*YZmHFFI_Ym #1"#m#*m@-mHFFFm1#m&,m"#100-**"-m.- *!'-,#1m"#mm#,m"'12',21m#1.#!'#1Ym ,-m "#m *-1m $!2-0#1m "#!'1'4-1m &m 1'"-m -.2'+'80m #*m .0-2-!-*-m "#m +32%#,'8!'A,m "#m *1m1#+'**1m!-,m#*m- (#2'4-m"#m- 2#,#0m3,m"#,1'""m"#m+32!'A,m*2m7m*m4#8Zm/3#m ,-m$#!2#mm*m4' '*'""m"#m*1m.*,21m+32%#,#'8"1Ym0m"#2#0+',0m*m"-1'1m"#*m +329%#,-m ^+7-0+#,2#m #*m _m #,m !"m #1.#!'#Zm &m 1'"-m ,#!#10'-m &!#0m #6.#0'+#,2-1m .0#4'-1m .0m .-"#0m "#2#0+',0m *m "-1'1m A.2'+Ym 1m .-0m #**-m /3#m #,!-,20+-1m "'12',2-1m 0,%-1m "#m "-1'1m #,m $3,!'A,m "#m *m #1.#!'#m ^ *m GYI_Ym 0m ,)-)*"#&O '&()!-.,m 1#m "#2#0+',Am /3#m *m !-,!#,20!'A,m A.2'+m #0m "#m KFm +m ^',)*#0m7m!-*YZmHFFK_Zm+'#,201m/3#m#,m ,#)*-#-O."&#(m#129m"#,20-m"#*m0,%-m"#m HFjJFm +m ^0##,#m 7m !-*YZm HFFI_Ym #!'#,2#+#,2#m 1#m &,m .3 *'!"-m .- *!'-,#1m "#m m#,m+#*A,m/3#m&,m.#0+'2'"-m(3120m*m"-1'1m"#m+329%#,-m.0m#12m#1.#!'#m ^&+,'j0"1m 7m !-*YZm HFGF\m -,8*#8j-m 7m !-*YZm HFGG_Ym 0m #*m +#*A,m 1#m &m !-+.0- "-m /3#m *m "-1'1m "#m &12m #*m IPm "#m +329%#,-m .0-.-0!'-,m 3,m .- *!'A,m !-,m3,m$0#!3#,!'m"#m+32!'A,m"#mGiKMIm m^&+,'j0"1m7m!-*YZmHFGF_Ymm T T II (.,)/#9(O O !+ TBMDOm- *!'-,#1m"#mm"#100-**"1m#,m,'+*#1m7m.*,21m.-0m-0"#,m!0-,-*A%'!-Ym#m.3#"#,m - 1#040m *1m "'12',21m "-1'1m "#m +329%#,-m ^#,m *%3,-1m !1-1m #6.0#1"1m #,m +Zm #,m -201m #,m Pm "#m 4i4m "#.#,"'#,"-m"#m*m.3 *'!!'A,_m32'*'8"1m#,m%#,-+1m"#m"'$#0#,2#m2+@-m7m!-,m"'$#0#,2#1m.*-'">1Ym,m 1-+ 0#"-m %0'1m *1m .- *!'-,#1m "#m +#*A,O "#100-**"1m &12m #*m +-+#,2-Zm 3,m "#m #**1m *m #* -0"m #,m #12#m 20 (-m ^-,8*#8j-m 7m !-*YZm HFGG_Ym g[m j#2'*jj,'20-1-30#Zm gg8j[m !'"-m "#m 1-"'-m 7m +#2'*j ,'20-130#Zmggg[mj,'20-1-jj+#2'*30#Ym m 1/$"($$ ,)-)*"#&O '&()!-.,O (#)O,,#)O ,#)*-#-O ."&#(O ),/'O 0/&!,O 329&$-.T .1(1T#$T , =.T#$+T ,329&$-.T &$-., T +.(#; T 1 T#$T ,32 "(>-T $%$0$-"( T #,2*#7m7m m KFm+m GNFm m Hm GiHFOm) m !#,,,Zm HFFFm gm IYFm+m GZMFFm m Hm GiHIKm) m m HFjJFm+m GHKm m Hm GiIFFm) m m HFjIFm+m KZIFFm m Hm Gi m '#,&-*"1m7m !-*YZmHFFIm 0##,#m7m!-*YZm HFFIm *"5#**m7m!-*YZm HFFJm '**m7m!-*YZm O'3-O m GmPm HZKFFm m Hm GiKFFm) m ,34O-.#0O m FYNjGmPm JIFm m Hm FYKi m 3m7m!-*YZmHFFKm ,34O-.#0O m GYLmPm JIFm m Hm Gi m 3m7m!-*YZmHFFKm m FYMKjGPm GHZFFFm m Jm GiJFm) m m FYMKjGYHPm GMZFFFm m Lm GiHJm m HFFJZm ,#.#/'O ./,!#/'O -/-*EO *"#m7m!-*YZm HFFKm /,/'O ,#.#/'O -.#0/'O ,)-)*"#&O '&()!-.,O ,)-)*"#&O m KFm+m GNFm m Hm GiGKLm) m m GHKm+m GNFm m Hm GiOFYKm) m EO&!(-O m HKm+m GFFm m Hm GiHOIm) m O'3-O m FYFLHKmPm HZKFFm m Hm O'3-O m FYFLHKmPm HZKFFm m Hm '&()!-.,O IJ *"#m7m!-*YZm HFFKm ',)*#0m7m!-*YZm HFFKm ',)*#0m7m!-*YZm HFFKm '*!&0'12m7m!-*YZm HFFLm FZOIi) mm #'*m7m-,"#Zm MIm HFFMm HYGFi) m #'*m7m-,"#Zm HHm HFFMm O #-/'O -.#0/'O ,34O-.#0O ,34O-.#0O (.,)/#9(O 0'/3#1m7m!-*YZm m Jm+m JZIFFm m Hm GiLLOm) m m GYKmPm JIFm m Hm GiHOJm) m '**m7m!-*YZmHFFMm JIFm m Hm GiHLKm) m '**m7m!-*YZmHFFMm 8j ggm HFFMm Gm+m8j GKm+m m &3#(O'2O gggm HYKm+m GZGGKm m Hm GiGJFm) m --.#0ZmHFFNm &3#(O'2O m KFm+m GZGGKm m Hm GiHKFm) m --.#0ZmHFFNm &3#(O'2O m JFm+m GZGGKm m Hm GiKKFm) m --.#0ZmHFFNm m FZHmPm GHKm m Hm GiJGKm m m FZOmPm GIZFFFm m Lm GiIFm m m FZIm7mFZJmPm HNIZNm m Hm GiLFm m m GPm OKFm m Hm GiIHHm) m m FZMPm OKFm m Hm GiKMJm) m ,#)*-#-O ."&#(O 0(O-.#0m ,--#O ,*m )&(/'O &3)*,-#/'m )&(/'O &3)*,-#/'m $ O ,"#-O "3*)!OO &#(."/-O ((/-O$ $ $ m BSDKm EFAT!m Cm BRFHDT*!m m FZJm7mGZHmPm jm Jm GiOLMm m T T FZMmPT ANFSBNFKT IGNOm T EFAT!T HT CT GiJMKm T BRTBNFT!T 31&m7m071,Zm HFGFm &5"#m7m!-*YZm HFGFm 2#.&#,1-,m7m !-*YZmHFGFm ',-'m7m!-*YZm HFGFm ',-'m7m!-*YZm HFGFm ', -(S 0# 1NTCABAm ,-**m7m!-*YZm HFGGmm #22m7m!-*YZm HFGGmT .-8 +$8S.T7T ".+MNTCABBT m BMEMCMCTTTTTTT 20-m $!2-0m /3#m .3#"#m *'+'20m *m '"#,2'$'!!'A,m "#m +32,2#1m #1m #*m "'1#@-m "#m *1m +#8!*1m "#m 1m ^.--*1_Ym m "'$#0#,!'m #,20#m &!#0m +#8!*1m "#m !320-m $+'*'1m -m +#8!*1m"#m-!&-m#1m#*m!-12#m7m#*m2'#+.-m,#!#10'-1m.0m*m"#2#!!'A,Ym-1m$!2-0#1m/3#m !-,"'!'-,,m *m #$'!'#,!'m #,m *m "#2#!!'A,m "#m +32,2#1m #,m 3,m +#8!*m 1-,m *m !*'""m "#*mm%#,A+'!-Zm*m.0#!'1'A,m"#m13m!3,2'$'!!'A,m7m#*m+<2-"-m31"-m.0m0#*'80m *m "#2#!!'A,m "#m 1Ym ,m *1m "'4#011m .*2$-0+1m .3 *'!"1m 1#m &,m "'1#@"-m & '23*+#,2#m+#8!*1m"#m"-1m&12m-!&-m$+'*'1Zm3,/3#m*mA.2'+m#1m*m+#8!*m"#m -!&-m 7m /3#m 0#"3!#m &12m *m +'2"m #*m !-12#m 7m #*m 2'#+.-m "#m 0120#-m "#m *m .- *!'A,m IK (.,)/#9(O O 0#1.#!2-m *m 31-m "#m +#8!*1m "#m !320-m $+'*'1Ym ,m 4#8m "#2#!2"m 3,m +32!'A,m #,m 3,m +#8!*m 1#m "# #m 0#.#2'0m #*m ,9*'1'1m #,m !"m m ',"'4'"3*m /3#m !-+.-,#m *m +#8!*Ym12#m.0-!#1-m1#m"#,-+',m"#!-,4-*3!'A,m7m#1m,#!#10'-m.0m',"'4'"3*'80m *m$+'*'m0#1.-,1 *#m"#m*m+32!'A,m^-* #02m7m!-*YZmHFFG_Ym,m*2#0,2'4m.0m*m "#2#!!'A,m"#m+32,2#1m#1m0#*'80m+#8!*1m#,m"-1m"'+#,1'-,#1m"#m+,#0m/3#m!"m +3#120m #129m .0#1#,2#m #,m "-1m B,'!-1m .--*1Ym 12m #1202#%'m 7m 1#m &m 31"-m m %0,m #1!*m#,m#*m#4O-,0#O^&22.[ii%#,-+#Y.30"3#Y#"3i+'8#2'**',%i_Ym3,/3#m "3.*'!0m *1m +#8!*1m 0#"3!#m *m 4#*-!'""m "#m *m "#2#!!'A,m "#m *-1m +32,2#1m 2+ '<,m 0#"3!#m*m',!#02'"3+ 0#m^"#1!02m$*1-1m.-1'2'4-1m-m02#$!2-1_Ym"#+91Zm#*m.1-m"#m *m"#2#!!'A,m',"'4'"3*m"#m*m$+'*'m-m"#!-,4-*3!'A,m,-m#1m,#!#10'-Ym T BMEMCMDTTTT -,m 40'1m *1m 2#!,-*-%>1m /3#m #6'12#,m .0m *m "#2#!!'A,m "#m 1m 7m /3#m &,m 1'"-m 31"1m.0m"#2#!20m+32!'-,#1m#,m.*2$-0+1m"#mYm#1"#m*m#*#!20-$-0#1'1m !-,m 2',!'A,m "#m 0-+30-m "#m #2'"'-m ^-+'m 7m #,')-$$Zm HFFL_Zm #*m m ^#!"O *, ),'(O &#+/#O ",)'.)!,*"3JO ^!**3+m 7m !-*YZm HFFF _Zm *m #1.#!20-1!-.>m "#m +11Zm *m #*#!20-$-0#1'1m !.'*0m #,m %0"'#,2#m #,m !-,"'!'-,#1m "#1,230*'8,2#1m -m *m "'%#12'A,m#,8'+92'!mm,'4#*m,3!*#-2>"'!-m^-+'m7m#,')-$$ZmHFFL_Zm&12m*1mB*2'+1m 2#!,-*-%>1m !-+-m *m #!"O -)&/.#)(O &.#(!m ^_m ^-,%m 7m !-*YZm HFFO_Zm *m 1#!3#,!'!'A,m +1'4m 2.O (,.#)(O +/(#(!m ^_m ^'%-*m 7m !-*YZm HFFO_m -m *m 32'*'8!'A,m"#mjm^.,#2N--#-.O-,O-),*.#)(M)(#4.#)(N#'O O&#!".JO ^&5"#mm7m!-*YZmHFGF_Ym3*/3'#0m"#m#121m2<!,'!1m1#m.3#"#m310m#,m#*mm .0m *m "#2#!!'A,m "#m +32,2#1Zm 1',m #+ 0%-Zm #*m +<2-"-m 1#*#!!'-,"-m "# #m .#0+'2'0m 3,m,9*'1'1m+1'4-m7m09.'"-Zm1>m!-+-m"#m+96'+m1#,1' '*'""Ymm -"-1m*-1m+<2-"-1m!'2"-1m,2#0'-0+#,2#m&,m1'"-m31"-1m.0m*m"#2#!!'A,m"#m1m ^!**3+m7m!-*YZmHFFFZm-* #02m7m!-*YZmHFFGZm'#,&-*"1m7m!-*YZmHFFI_m.#0-m#*m+<2-"-m +91m !-+B,m .0m #*m m &m 1'"-m *m "#2#!!'A,m "#m *1m +32!'-,#1m m .02'0m "#m *m "'%#12'A,m !-,m ,3!*#11m #1.#!>$'!1m "#m &#2#0-"B.*#6m ^'%30m GYK_Ym *m .0-!#"'+'#,2-m !-+B,m #1m +.*'$'!0m 3,m 0#%'A,m "#*m %#,m "#m ',2#0<1m +#"',2#m m !-,m !# "-0#1m #1.#!>$'!-1m7m+0!"-1m!-,m3,m$*3-0A$-0-m"'12',2-m.0m!"m#620#+-mKam^7#mMFF_m7m Iam^7#mNFF_Ym*m.0-"3!2-m"#m*mm#1m"#1,230*'8"-m7m0#,230*'8"-m"#m+-"-m /3#m *-1m *#*-1m +32"-1m 1#m +#8!*,m !-,m *-1m *#*-1m 1'*4#120#1m 7m $-0+,m *-1m &#2#0-"B.*#6Ym *m ',!3 01#m !-,(3,2+#,2#m !-,m *m #,"-,3!*#1m #1.#!>$'!m "#m &#2#0-"B.*#6m1#m"'%'#0#,m1A*-m/3#**-1m$0%+#,2-1m/3#m!-,2'#,#,m3,m+32!'A,Ymm IL O (.,)/#9(O m 4'13*'8!'A,m 1#m 0#*'8m +#"',2#m %#*#1m 4#02'!*#1m "#m !0'*+'"m #,m .*2$-0+1m !-+-m#*mjmm,*78#0m2*m7m!-+-m.3#"#m4#01#m#,m*m'%30mGYKYm,m.0'+#0m *3%0m #*m $0%+#,2-m "#*m %#,m "#m ',2#0<1m 1#*#!!'-,"-m #1m +.*'$'!"-m +#"',2#m 3,m !# "-0m "'0#!2-m +0!"-m $*3-0#1!#,2#+#,2#m !-,m 7#m MFFZm 7m !-,m 3,m !# "-0m 0#4#01-m +0!"-m $*3-0#1!#,2#+#,2#m !-,m 7#m NFFYm #1.3<1m "#m *m $-0+!'A,m "#*m &#2#0-"B.*#6m *1m +3#1201m 1-,m ',!3 "1m !-,m #*m .0Zm .-12#0'-0+#,2#Zm 1#0m "#1,230*'8"1m ^"#2**"-m #,m *m '%30m GYJ_m 7m !0%"1m #,m 3,m %#*m 4#02'!*m "#m !0'*+'"m .0m 4'13*'80*1m +#"',2#m #*m jm JIFFYm 0m !"m %#*m 1#m .0-"3!#,m "-1m'+9%#,#1[m3,m.0-"3!'"m.-0m*m1#@*m/3#m#+'2#m#*m$*3-0A$-0-m',!-0.-0"-m#,m#*m !# "-0m "'0#!2-m ^7#m MFFZm 0-(-_m 7m *m -20m *m 1#@*m .0-"3!'"m .-0m #*m $*3-0A$-0-m ',!-0.-0"-m #,m #*m !# "-0m 0#4#01-m ^7#m NFFZm 4#0"#_Ym -0m *-m 2,2-Zm #,m #*m !,*m "#*m 7#m MFFm .-"0#+-1m 4#0m #*m $0%+#,2-m /3#m 0!m *m *-,%'23"m "#1"#m #*m #620#+-m Kam &12m #*m .3,2-m "#m *m "'%#12'A,m ^/3#m #1m #*m +'1+-m *3%0m "-,"#m 1#m &m $-0+"-m #*m &#2#0-"B.*#6m 7m .-0m *-m 2,2-m 2+ '<,m "-,"#m #129m *m +32!'A,_Ym '#,201m /3#m #,m #*m !,*m7#mNFFm.-"0#+-1m4#0m#*m$0%+#,2-m/3#m 0!m*m*-,%'23"m"#1"#m#*m#620#+-m Iam&12m#*m.3,2-m"#m*m"'%#12'A,Ymm13+m"#*m2+@-m"#*m$0%+#,2-m"'%#0'"-m#,m#*m !,*m7#mMFFm7m#*m2+@-m"#*m$0%+#,2-m"'%#0'"-m#,m#*m!,*m7#mNFFm2'#,#m/3#m !-',!'"'0m!-,m#*m2+@-m2-2*m"#*m$0%+#,2-m+.*'$'!"-m2*m!-+-m.3#"#m- 1#0401#m #,m#*m%#*m"#m*m'%30mGYKm^LFFQJFFSGFFFm. _Ym m IM (.,)/#9(O O m (&30 TBMFOm#2#!!'A,m"#m3,m+32!'A,m#,m3,m.- *!'A,m"#mm#,m+#*A,m#,m3,m%#*m"#m!0'*+'"m 4#02'!*m"#mjmJIFFYmm*m'8/3'#0"m1#m- 1#04m#*m%#*m4'13*'8"-m#,m#*m!,*mMFFZmm*m"#0#!&m#,m#*m !,*m NFFYm ,m !"m !,*m 1#m 4'13*'8m #*m $0%+#,2-m "'%#0'"-m "#1"#m 3,-m "#m *-1m #620#+-1Zm 7m /3#m #*m !# "-0m "'0#!2-m ^KaZm 0-(-_m **#4m #*m +0!(#m MFFm +'#,201m /3#m #*m !# "-0m 0#4#01-m ^IaZm 4#0"#_m **#4m #*m +0!(#m.0m#*mNFFYmm13+m"#*m2+@-m"#m*-1m$0%+#,2-1m"#2#!2"-1m#,m!"m!,*m^MFF[mLFFm. m QmNFF[mJFFm. _m"# #m!-',!'"'0m!-,m#*m2+@-m2-2*m"#*m$0%+#,2-m1',m"'%#0'0m4'13*'8"-m#,m#*m#620#+-m 13.#0'-0m"#*m%#*m^GFFFm. _Ym m 0m#*m.0-!#1-m"#m"'%#12'A,m"#*m&#2#0-"B.*#6m1#m&,m"#1!0'2-m*%3,1m#,"-,3!*#11m ^3&0+,,m7m!-*YmHFFKZm-3'*m7m!-*YZmGOOKZm1&*m7m!-*YZmGOOKZm'**m7m!-*YZmHFFJ _Ymm #,"-,3!*#1m +91m !-+3,+#,2#m 32'*'8"m .0m #*m m #1m &O#620>"m "#m .'-m ^&,3_m^*#7)-51)'m7m!-*YZmGOON_Ym1m3,m#,"-,3!*#1m/3#m!2Bm"'%'0'#,"-m#*mm "#m !"#,m 1#,!'**Ym #m &m "#+-120"-m 2+ '<,m /3#m -201m #,"-,3!*#11m !-+-m *1m #620>"1m "#m (3">m 1-,m #$'!'#,2#1m .0m "#2#!20m +32!'-,#1m +#"',2#m #*m +<2-"-m m ^'**m 7m !-*YZm HFFJ _Ym m #*#!!'A,m "#m *m #,8'+m 2+ '<,m .3#"#m 1#0m 3,m $!2-0m IN O (.,)/#9(O *'+'2,2#m .0m *m 1#,1' '*'""m "#*m +<2-"-Zm 7m 1#m "#+-120Am /3#m *m 32'*'8!'A,m "#m #620!2-m "#m &m (3,2+#,2#m !-,m #*m +<2-"-m "#m 4'13*'8!'A,m "#m jm JIFFm #0m #*m +91m 1#,1' *#m .0m *m "#2#!!'A,m "#m 1m #,m +#8!*1m "#m Nm $+'*'1m ^"'*3!'A,m GiGLm "#*m *#*-m+32"-m#,m3,m#1.#!'#m"'.*-'"#_m^0##,#m7m!-*YZmHFFI_Ymm#,8'+m&m0#!-,-!#m *-1m &#2#0-"B.*#6m !-,m *m .0#$#0#,!'m im Um im Vm im Um iZm 7m 0#!-,-!#m !-,m +#,-0m #1.#!'$'!'""mimVmimVmimTmimVmim7m2-"4>m!-,m+#,-1mim^*#7)-51)'m7m !-*YZm GOON\m ,%m 7m !-*YZm HFFF_Ym *m +'1+-m 2'#+.-Zm #12m #,8'+m 2'#,#m 3,m 3#,m #1.#!'$'!'""m #,m #*m 0#!-,-!'+'#,2-m "#m &#2#0-"3.*#6m #,m 3,m "'*3!'A,m *<*'!m "#m G[GLYm 1m .-0m #**-Zm /3#m 1#m 32'*'8m .0m *m "#2#!!'A,m "#m 1m #,m +#8!*1m "#m Nm $+'*'1m #,m #1.#!'#1m "'.*-'"#1Ym ,m !+ '-Zm *m #,8'+m ()m ^!*-,"m m .02'0m "#m 3,m %#,m /3#m !-"'$'!m.-0m3,m#,"-,3!*#1m'"#,2'$'!"m#,m,#)*-#-_Zm0#!-,-!#m2-"-1m*-1m2'.-1m "#m +32!'-,#1m !-,m *m +'1+m #1.#!'$'!'""m #,m "'*3!'-,#1m *<*'!1m "#m G[LJm ^0'/3#1m 7m !-*YZm HFFM_Ym ,m !3,2-m *m 1.#!2-m #!-,A+'!-Zm *m - 2#,!'A,m !-+#0!'*m "#m + 1m #,"-,3!*#11m 2'#,#,m 3,m !-12#m *2-Zm 1',m #+ 0%-Zm .0m *m - 2#,!'A,m "#m &m 1#m &,m .3 *'!"-m.0-2-!-*-1m.0m- 2#,#0m3,m#620!2-m"#m.'-m/3#m$3,!'-,m#$'!'#,2#+#,2#m7m 0#"3!#m #*m !-12#m !-+.0"-m !-,m *m - 2#,!'A,m "#m *m #,8'+m .30'$'!"m ^,%m 7m !-*YZm HFFF_Ym 30,2#m*-1mB*2'+-1m@-1m 1#m &,m &#!&-m #123"'-1m !-+.0,"-m*m#$'!'#,!'m"#m + 1m#,"-,3!*#11m#,m*m"#2#!!'A,m"#m.-*'+-0$'1+-1m+#"',2#m!-Ym-1m 0#13*2"-1m - 2#,'"-1m 1-,m '"<,2'!-1m "#+-120,"-m /3#m *m #$'!'#,!'m #1m .09!2'!+#,2#m '%3*m ^-,-m 7m !-*YZm HFGG_Ym -0m *-m 2,2-Zm *m 32'*'8!'A,m "#m 3,m 3m -20m #,"-,3!*#1m "#.#,"#09m "#*m 2'.-m "#m m #1.#0"-m 1#%B,m #*m +329%#,-m 32'*'8"-Zm #*m !-12#m "#m *m +'1+m7m"#m*m0#%'A,mm#123"'0m^#3,%m7m!-*YZmHFFK\m-"%1-,m7m#**1ZmGOMM_Ymm ,m 4#,2(m '+.-02,2#m "#*m +<2-"-m #,8'+92'!-Zm !-,$0-,2"-m !-,m *1m -201m 2<!,'!1m !'2"1m,2#0'-0+#,2#Zm#1m/3#mm*m4#8m/3#m1#m"#2#!2m*m+32!'A,Zm2+ '<,m1#m"#2#!2m 13m *-!*'8!'A,m "#,20-m "#*m %#,Ym -12#0'-0+#,2#Zm +#"',2#m *m 1#!3#,!'!'A,m "#*m $0%+#,2-m #,m *m $+'*'m +32,2#m 1#m .3#"#m 4'13*'80m #,m #*m !0-+2-%0+m 1'm *m +32!'A,m1#m#,!3#,20m#,m&-+-!'%-1'1m-m&#2#0-!'%-1'1Ym m.02'0m"#*m@-mHFFOm1#m#+.#8Amm310m-20-m+<2-"-m"#m"#2#!!'A,m"#m*-1m$0%+#,2-1m +32"-1[m*m2#!,-*-%>m"#m#!"O-)&/.#)(O&.#(!m-m,9*'1'1m"#m!3041m"#m"'1-!'!'A,m "#*mm^-,%m7m!-*YZmHFFO\m"7m7m!-*YZmHFFO_Ym12m2<!,'!m1#m 1m#,m+-,'2-0'80m*m !',<2'!m "#m "'1-!'!'A,m "#m *-1m $0%+#,2-1m +.*'$'!"-1m 7m 0#,230*'8"-1m .0#4'+#,2#m.0m.0-4-!0m*m$-0+!'A,m"#m&#2#0-"B.*#6Ym#"',2#m#12m.*'!!'A,m 1#m.3#"#m"#2#0+',0m*m+m^'*,./,O'&.#(!_m"#m*-1m+.*'!-,#1m.0m!-+.0- 0m 1'm&7m.0#1#,!'m"#m+32!'A,m-m,-Ymm!-+.*#+#,20'#""m#,20#m"-1m!"#,1m"#m3,m ',"'4'"3-m1'*4#120#m1#09m 1-*32m7Zm.-0m*-m2,2-Zm*m#12 '*'""m1#09m*2Zm.-0m*-m/3#m13m 2#+.#0230m"#m"'1-!'!'A,m1#09m+7-0Ym',m#+ 0%-Zm1'm*1m!"#,1m0#,230*'8"1m IO (.,)/#9(O O .-1##,m3,m&#2#0-"B.*#6Zm13m#12 '*'""m1#09m+#,-0m7m13m2#+.#0230m"#m"'1-!'!'A,m 1#09m +#,-0m 2+ '<,m ^#(#+.*-m #,m *m '%30m GYL_Ym 12m 2<!,'!m 7m &m 1'"-m 32'*'8"m #,m 20'%-m ^-,%m 7m !-*YZm HFFO_Zm 2-+2#m ^"7m 7m !-*YZm HFFO_m 7m ,#)*-#-O ^31&m 7m 071,Zm HFGF_m 7m .3#12m m .3,2-m 0#!'#,2#+#,2#m #,m ,3#120-m * -02-0'-m ^#0%0#!&#Zm !-+3,'!!'A,m.#01-,*_Ym m m (&30 T BMGOm (#+.*-m "#m !304m "#m "'1-!'!'A,m "#m $0%+#,2-1m +.*'$'!"-1m 7m 0#,230*'8"-1Ym #m .3#"#m "#2#0+',0m*m.0#1#,!'m"#m3,m&#2#0-"B.*#6m.-0/3#m.0#!#m3,m.'!-mm3,m2#+.#0230m+#,-0m^MMZLE_mm *m "#2#0+',"m .0m *m +#8!*m 1'*4#120#m ^MOZKE_Ym 1m 3,'""#1m "#m 1#@*m "#m $*3-0#1!#,!'m 1#m +'"#,m #,m $3,!'A,m"#m*m4#*-!'""m"#m!+ '-m"#m*1m3,'""#1m"#m$*3-0#1!#,!'m0#*2'4m^_m!-,m#*m2'#+.-m^_m^j"m ^_mim"_m^$3#,2#[m31&m7m071,ZmHFGF_Ym m m .#10m "#m *m #$'!'#,!'m .0- "m "#m *-1m +<2-"-1m +#,!'-,"-1m ,2#0'-0+#,2#Zm *m 2#,"#,!'m !23*m #1m "#m 310m -20-1m "-1m +<2-"-1m ,-m +#,-1m #$'!'#,2#1[m jm 7m Ym m 2<!,'!m "#m jm .0#!#m #120m ","-m +37m 3#,-1m 0#13*2"-1m #,m #1.#!'#1m"#m.*,21m!-+-m0(O-.#0m^&5"#m7m!-*YZmHFGF_Ym,m!3,2-mm*1m,3#41m 2#!,-*-%>1m"#m1#!3#,!'!'A,Zm*1m+91m31"1m#,mm1-,mJKJm()'O+/(,O O #m ^-!&#m ..*'#"m !'#,!#_m #m &&/'#(O I-*#6JO ()'O (&34,Ym ,m 2-+2#m 1#m &,m32'*'8"-m1'+3*29,#+#,2#m+91m"#mGHYFFFm+3#1201m.0m,*'80m"'12',2-1m%#,#1m #,m3,m1-*m.*!mJKJ '!-'2#0m*2#m^_m^'%-* 7m!-*YZmHFFO_YmmB*2'+m',,-4!'A,m #,m#12#m1#,2'"-m&m1'"-m32'*'80m*1m2#!,-*-%>1m"#m1#!3#,!'!'A,m+1'4m!-+ ',"1m !-,m *m #* -0!'A,m "#m +#8!*1m #,m "'12',21m "'+#,1'-,#1m ^1'm 7m !-*YZm HFGG_Ym 0m !-,$'0+0m 3,m +32!'A,m +#"',2#m 1#!3#,!'!'A,m &!#m $*2m 3,m !- #0230m "#*m %#,-+m"#mHFjIFm#,m,#)*-#-O^11-51)7m7m!-*YZmHFGF_Ym,m00-8m^,34O-.#0_m7m#,m 20'%-m ^,#.#/'O /,/'_m 1#m &,m "#2#!2"-m #$'!'#,2#+#,2#m +32!'-,#1m +#"',2#m *m 1#!3#,!'!'A,m "#m $0%+#,2-1m "#m m !-,m **3+',m #,m 3,m 2-2*m "#m MLNm ',"'4'"3-1m !-+ ',9,"-*-1m#,m+#8!*1m"#m&12mOJm',"'4'"3-1m^1'm7m!-*YZmHFGG_Ymm JF O (.,)/#9(O *m +<2-"-m m !-+ ',"-m !-,m *m 1#!3#,!'!'A,m +1'4m 7m *m .*'!!'A,m "#m +#8!*1m#,m"'12',21m"'+#,1'-,#1m.0#!#m.0#1#,20m40'1m4#,2(1Ym,m.0'+#0m*3%0m *m.*'!!'A,m"#m40'1m+#8!*1m.#0+'2#m*m!-,$'0+!'A,m"#*m+32,2#m7m"'1+',37#m*m .0- '*'""m"#m#00-0Ym"#+91Zm!-,m*m'"#,2'$'!!'A,m"#m*m$+'*'m+32,2#m1#m- 2'#,#m 2+ '<,m*m',$-0+!'A,m"#*m2'.-m"#m!+ '-m,3!*#-2>"'!-m7m"#m13m.-1'!'A,Zm1>m!-+-m"#m 13m #$#!2-m #,m *m 1#!3#,!'m +',-!>"'!Ym 20m 4#,2(m #1m /3#m 1#m "'1+',37#m *m ,#!#1'""m"#m31-m"#m!# "-0#1m+0!"-1m!-,m$*3-0A$-0-1m,'m2+.-!-m#,"-,3!*#11Ym ',*+#,2#Zm #1m 3,m +<2-"-m #1!* *#m m "'12',2-1m ,'4#*#1m .3"'<,"-1#m .*'!0m .0m 2,2-1m %#,#1m !-+-m 1#m ,#!#10'-m - 2#,'#,"-m 3,m %0,m .0#!'1'A,m #,m *m "#2#!!'A,m "#m +32!'-,#1m7m#,m3,m.#0>-"-m"#m2'#+.-m+37m0#"3!'"-m^1'm7m!-*YZmHFGG_Ymm m BMEMCMETTTTT m 21m "#m +32!'A,m - 2#,'"m &m 1'"-m 40' *#m #,m *1m "'12',21m .*2$-0+1m "#m m "#100-**"1m &12m &-0m ^ *m GYI_Zm #,m ,#)*-#-O &m 1'"-m '"#,2'$'!"m 3,m+32!'A,m!"mIFFm m^0##,#m7m!-*YZmHFFI_Zm#,m+>8m3,m!"mKFFm) m^'**m7m!-*YZm HFFJZ_m7m#,m00-8m3,m!"mHOJm m^'**m7m!-*YZmHFFM_Zm+'#,201m/3#m#,m!# "m*m21m "#m +32!'A,m #1m "#m Gm !"m m ^*"5#**m 7m !-*YZm HFFJ_Ym !23*+#,2#m *m "#,1'""m "#m +32!'A,m+91m*2m&m1'"-m"#1!0'2m#,m20'%-m2#20.*-'"#m^GiJFm) _m7m20'%-m&#6.*-'"#m ^GiHJm ) _m ^*"#m 7m !-*YZm HFFK_Ym ,m !3,2-m *m +#*A,m 1#m &m "#100-**"-m 3,m .- *!'A,m !-,m3,m21m"#m+32!'A,m"#mGiKMIm m^&+,'j0"1m7m!-*YZmHFGF_Ym *m +<2-"-m m .#0+'2#m *m '"#,2'$'!!'A,m "#m *1m $+'*'1m +32,2#1Ym ,m 4#8m '"#,2'$'!"1m *1m $+'*'1m &!#m $*2m 1#!3#,!'0m #*m $0%+#,2-m "-,"#m 1#m #,!3#,20m *m +32!'A,m .0m .-"#0m .0#"#!'0m 131m #$#!2-1Ym # #0#+-1m ,*'80m 1'm 1#m 202m "#m 3,m +32!'A,m #,m 0#%'A,m ',20A,'!m -m #6A,'!Ym ,m !1-m "#m *-!*'801#m #,m 3,m #6A,Zm #6+',0#+-1m 1'm #*m !+ '-m "#m ,3!*#A2'"-m .0-"3!#m 2+ '<,m 3,m !+ '-m "#m +',-9!'"-m -m 1'Zm .-0m #*m !-,200'-Zm #1m 1'*#,!'-1Ym ,m !1-m "#m .0-4-!0m 3,m !+ '-m "#m +',-9!'"-m2+ '<,m"# #0#+-1m!-+.0- 0m1'm#*m!+ '-m.0-4-!"-m.3#"#m$#!20mm *m#1203!230m20'"'+#,1'-,*m"#m*m.0-2#>,Ym*m!1-m+91m#620#+-m#1m/3<*m#,m#*m/3#m#*m !+ '-m "#m +',-9!'"-m .0-4-!m 3,m !-"A,m b12-.cm m *m .0-2#>,m .0-"3!'#,"-m 3,m ',2#003.!'A,m "#m *m 20"3!!'A,Ym -0m *-m 2,2-Zm *1m +32!'-,#1m '"#,2'$'!"1m #,m 0#%'A,m !-"'$'!,2#m"#m*m1#!3#,!'m,3!*#-2>"'!m.3#"#,m!*1'$'!01#m#,[m jm +32!'-,#1m 1',m 1#,2'"-GO #,m *1m !3*#1m #*m !+ '-m ,3!*#-2>"'!-m .0-4-!m 3,m !-,4#01'A,m"#m3,m+',-9!'"-mm3,m!-"A,m12-.Zm',2#003+.'#,"-m1>m*m!-00#!2m 20"3!!'A,m"#m*m.0-2#>,Ym JG (.,)/#9(O O jm+32!'-,#1m1312'232'41m-m,-m1',A,'+1[m#,m*1m!3*#1m#*m!+ '-m,3!*#-2>"'!-m 1-!'"-mm*m+32!'A,m.0-4-!m3,m!+ '-m"#m+',-9!'"-Ym12#m!+ '-m/3#"m 2+ '<,m!-,"'!'-,"-m.-0m*1m!0!2#0>12'!1m/3>+'!1m"#*m,3#4-m+',-9!'"-Zm /3#m.3#"#m-!1'-,0m!+ '-1m!-,$-0+!'-,*#1m7i-m$3,!'-,*#1m"#m*m.0-2#>,Ym jm+32!'-,#1m1'*#,!'-11m-m1',A,'+1[m#,m*1m!3*#1m*m+32!'A,m,3!*#-2>"'!m,-m .0-4-!m3,m!+ '-m#,m#*m!-"A,m7m.-0m*-m2,2-m,-m&7m3,m!+ '-m+',-!>"'!-m 7m*m.0-2#>,m+32,2#m1#09m'"<,2'!mm*m1'*4#120#Ym m 0m3,m2#!,-*-%>m 1"m#,m*m%#,<2'!m',4#01m!-+-m#*mZm*1m+32!'-,#1m 1',m 1#,2'"-m 7m 1312'232'41m 1-,m *1m !-,1'"#0"1m +91m '+.-02,2#1m 7m /3#m .3#"#,m $#!20m .-2#,!'*+#,2#m m *m $3,!'-,*'""m "#m *m .0-2#>,m 7m .-0m *-m 2,2-Zm "0m *3%0m m 3,m,3#4-m$#,-2'.-Ym30,2#m*m!-,1203!!'A,m"#m*m.- *!'A,m0#13*2m#1#,!'*m!-,-!#0m *m.0- '*'""m"#m/3#m#12-m.3#"m13!#"#0m#,m*m0#%'A,m,*'8"m^!**3+m7m!-*YZm HFFF _Ym 1m '+.-02,2#m ,*'80m 3,m 0#%'A,m "#*m %#,m #,m *m !3*m .-"+-1m #,!-,200m .-2#,!'*+#,2#m +91m +32!'-,#1m 2'.-m 1',m 1#,2'"-m 7m 1312'232'41Ym 0m #1!-%#0m 3,m 0#%'A,m A.2'+m 1#m "'1.-,#m "#m &#00+'#,21m !-+-m #*m .0-%0+m m ^))(O *.#'#4O .)O ..O &.,#)/-O -#)(-_Zm /3#m .#0+'2#m !*!3*0m *m .0- '*'""m "#m - 2#,#0m +32!'-,#1m .3,23*#1m #,m 3,m "#2#0+',"m 0#%'A,m 7m /3#m $#!2#,m m *m #1203!230m "#m *m .0-2#>,m ^&22.[ii555Y.0-5# Y-0%i!-""*#_m ^'**m 7m !-*YZm HFFI_Ym m#1m3,m.0-%0+m/3#m+3#120m2-"1m*1m+32!'-,#1m/3#m.-"0>,m-!300'0m#,m 3,m 1#!3#,!'m "#2#0+',"m #,m $3,!'A,m "#*m 2'.-m "#m +329%#,-m 32'*'8"-m 7m *m +'1+-m 2'#+.-Zm,*'8m#,m!"m.-1'!'A,m*m.0- '*'""m"#m$#!20mm*m$3,!'-,*'""m"#m*m .0-2#>,m#,m!1-m"#m!+ '-Ym ,m 4#8m '"#,2'$'!"m 3,m +32!'A,m 1',m 1#,2'"-m .3#"#m #12'+01#m !A+-m $#!209m m *m $3,!'-,*'""m "#m *m .0-2#>,Ym 0m .-"#0m 0#*'80m 3,m .0#"'!!'A,m "#*m #$#!2-m "#m *m +32!'A,m #6'12#,m .0-%0+1m ',$-0+92'!-1m #1.#!>$'!-1m 1"-1m #,m *m &-+-*-%>m !-,m 1#!3#,!'1m.0-2#'!1m"#m-201m#1.#!'#1Ym,m#(#+.*-m#1m#*mm^,)$.O&#!(O &.O +/(-O (O 0&/.O -_m ^&22.[ii555Y.0-5# Y-0%i.01#1,.i\m 7*-0m 7m 0##,#Zm HFFI\m '**m 7m !-*YZm HFFI_m 7m #*m .0-%0+m m ^),.#(!O(.)&,(.O,)'O)&,(._m /3#m #$#!2B,m *m .0#"'!!'A,m #,m 1#m m 3,m jm ^)-#.#)(N*# #O .,.#0O -#O )&O &#!('(.O ,"O ))&_m 7m #,m 1#m m *1m !0!2#0>12'!1m $>1'!-j/3>+'!1m "#m *-1m +',-9!'"-1m^&22.[ii *-!)1Y$&!0!Y-0%i1'$2iY&2+*\m%m7m#,')-$$ZmHFFG_Ym *mm.-0m*-m2,2-Zm.0-.-0!'-,[m JH O (.,)/#9(O jm32!'-,#1m',"'4'"3*#1m/3#m.3#"#,m.0-"3!'0m1#0'#1m*<*'!1m/3#m.0-4-/3#,m ,3#4-1m $#,-2'.-1Ym 12m %0"!'A,m $#,-2>.'!m *'%"m m 3,m 1#0'#m *<*'!m .3#"#m .0-6'+0,-1mm!-,-!#0m*m$3,!'-,*'""m"#*m%#,Ym jm#0+'2#m!0#0m7m!0!2#0'80m3,m,3#4m40'#""m%#,<2'!m#,m#*m%#0+-.*1+m "#m#1.#!'#1m!3*2'4"1m"#m',2#0<1Ym m ,m #*m !1-m "#m *-1m +32,2#1m '"#,2'$'!"-1m +#"',2#m m #1m ,#!#10'-m 32'*'80m 0#20-!038+'#,2-1m .0m - 2#,#0m *m +32!'A,m '1*"m #,m 3,m $-,"-m %#,<2'!-m "#1#"-Ym # #m 2#,#01#m #,m !3#,2m /3#m *-1m +32,2#1m "#2#!2"-1m +#"',2#m m **#4,m ',!-0.-0"1m ,-m 1A*-m *m +32!'A,m "#2#!2"m #,m #*m %#,m "#m ',2#0<1m 1',-m 2+ '<,m +3!&1m -201m +32!'-,#1m "'120' 3'"1m *m 80m #,m #*m 0#12-m "#*m %#,-+m ^*"#m 7m !-*YZm HFFK_Ym 0m .-"#0m '"#,2'$'!0m !-,m +7-0m #6!2'23"m *m $3,!'-,*'""m "#m 3,m %#,m ,-m 12m!-,m#,!-,200m#*m+32,2#m7m- 1#040m#*m$#,-2'.-m1',-m/3#m"#+91Zm#1m,#!#10'-m - 2#,#0m #*m +32,2#m '1*"-m "#m -201m .-1' *#1m +32!'-,#1m "'!'-,*#1Ym A*-m "#m #12#m +-"-m1#m.-"0>m!-,$'0+0m!-,m!#02#8m/3#m*m+32!'A,m'"#,2'$'!"m#1m*m0#1.-,1 *#m "#m !'#02-m $#,-2'.-Ym -0m *-m 2,2-m #,m *m $1#m $',*m "#*m .0-2-!-*-m "#m m 1#m "# #,m #$#!230m 40'-1m 0#20-!038+'#,2-1Zm #,20#m #*m +32,2#m 7m #*m 1'*4#120#m "#m *m +'1+m 40'#""Zm.0m.-"#0m'1*0m*m+32!'A,m"#m',2#0<1m^*"#m7m!-*YZmHFFK_Ym T BMEMCMFTTTTT 6'12#,m .*2$-0+1m "#m m #,m ,3+#0-11m #1.#!'#1m 4#%#2*#1m 7m ,'+*#1Ym m %0,m 4#,2(m "#*m m #1m /3#m .3#"#m 32'*'801#m #,m #1.#!'#1m "'.*-'"#1m -m .-*'.*-'"#1Zm !-,m "'$#0#,2#1m 2+@-1m "#m %#,-+1m 7m /3#m .-1#,m !3*/3'#0m 2'.-m "#m 0#.0-"3!!'A,m ^0)*#7m 7m ,%Zm HFFN_Ym *m B,'!-m 0#/3#0'+'#,2-m #1m .-"#0m +320m *1m 1#+'**1m-m#*m.-*#,m.0m.-12#0'-0+#,2#m!0#!#0m*1m%#,#0!'-,#1m1'%3'#,2#1m7m#620#0m #*m m .0m ,*'80*-Ym ,m *m *m GYIm 1#m +3#120m 3,m 0#13+#,m "#m *%3,1m "#m *1m .- *!'-,#1m "#m m "#100-**"1m &12m #*m +-+#,2-m "#+-120,"-m /3#m #12m 2<!,'!m#1m.*'! *#m#,m"'$#0#,2#1m#1.#!'#1Ym #m"#12!0m2+ '<,m*m40' '*'""m"#*m 2+@-m "#m *-1m %#,-+1m #,m *-1m !3*#1m 1#m &m .*'!"-m *m 2<!,'!Ym -1m 2+@-1m #,m -0%,'1+-1m"'.*-'"#1m 0!,m"#1"#m*1mGFFm m#,mEO&!(-m^'*!&0'12m7m!-*YZmHFFL_m &12m*1mKZIFFm m"#m),/'O0/&!,m^*"5#**m7m!-*YZmHFFJ_Ymm2<!,'!m2+ '<,m&m 1'"-m #$'!'#,2#m #,m -0%,'1+-1m .-*'.*-'"#1m !-+-m ,#.#/'O ./,!#/'O 13 1.EO /,/'Zm 2#20.*-'"#m^*"#m7m!-*YZmHFFK_m7O,#.#/'O-.#0/'ZO&#6.*-'"#m^*"#m7m!-*YZmHFFK_Zm#,m #12#m!1-m*-1m2+@-1m"#m%#,-+1m 0!,m&12m*1mGMYFFFm m"#m,#.#/'O-.#0/'Em m21m"#m+32!'A,m#1m3,-m"#m*-1m4*-0#1m+91m'+.-02,2#1m.0m"#2#0+',0m1'm3,m .- *!'A,m"#mm#1m#$'!'#,2#Ym39,2-m+7-0m1#m*m.0- '*'""m"#m#,!-,200m JI (.,)/#9(O O +32,2#1m#,m3,m.*2$-0+m"#mm+91m#$#!2'4m1#09Ym1m211m"#m+32!'A,m#,m .- *!'-,#1m "#m m "#m .*,21m 0!,m 3,m +.*'-m 0,%-Ym ,m "'.*-'"#1m "#1"#m GiLFm) m#,m,--#O,*m^2#.&#,1-,m7m!-*YZmHFGF_m&12mFZKiGm m#,m,34O-.#0m^3m 7m !-*YZm HFFK_m +'#,201m /3#m #,m #1.#!'#1m .-*'.*-'"#1m #,!-,20+-1m 211m "#1"#m GiHJm m #,m,#.#/'O-.#0/'m^*"#mm7m!-*YZmHFFK_m&12mGiOLMm m#,m,"#-O"3*)!m^,-**m7m !-*YZmHFGG_Ym# #m2#,#01#m#,m!3#,2m/3#m#,m#*m.0-!#"'+'#,2-m"#m!9*!3*-m,-m1'#+.0#m1#m &,m 31"-m *1m +'1+1m 40' *#1m 7m .-0m *-m 2,2-Zm 0#13*2m "'$>!'*m &!#0m !-+.0!'-,#1m #,20#m #1.#!'#1m #,m 2<0+',-1m %#,#0*#1Ym 0m *%3,1m .- *!'-,#1m "#m m 1#m&,m "#100-**"-m #123"'-1m $#,-2>.'!-1m "#m *-1m +32,2#1m #,m "'12',2-1m 2#('"-1m 7m "'$#0#,2#1m $1#1m "#m !0#!'+'#,2-Ym 1m 1#1m "#m "2-1m "#m #121m .- *!'-,#1m .#0+'2#,m - 1#040m $#,-2'.-1m +32,2#1m #,m #*m "#100-**-m "#m *m .*,2Zm "#*m $032-Zm "#m *m $*-0m -m "#m *-1m !-2'*#"-,#1Zm#,20#m-20-1Ym*mm^(#.6OO","O(O6()'#+/O6!.&_m"'1.-,#m "#m 3,m 1#m "#m "2-1m ^" _m /3#m .#0+'2#m 1-*'!'20m 1#+'**1m "#m +32,2#1m "#m "'12',21m #1.#!'#1m !-+-m 2-+2#Zm !-*8Zm %3'1,2#m -m +#*A,m ^&22.[ii555Y4#01'**#1Y',0Y$0i30%4i2'**',%Y&2+_Ym + '<,m #6'12#,m -201m !-+-m *m "#*m !#,20-m )."'-.O-,"O(-.#./.m /3#m .0-.-0!'-,m +32,2#1m "#m 3,m .- *!'A,m "#m m "#m 20'%-Ym 0m ,#)*-#-m #6'12#m 3,m 1#04'!'-m 5# O ^&22.[ii2'**',%Y$&!0!Y-0%_m "-,"#m 1#m .3#"#m #,!-,200m 2-"m *m ',$-0+!'A,m !#0!m "#m *-1m +32,2#1m 7m !0!2#0'8"-1m7m3,m1#04'!'-m"#m'"#,2'$'!!'A,m.0m%#,#1m"#m',2#0<1Ym+ '<,m#6'12#,m *%3,1m #+.0#11m .0'4"1m /3#m &,m 32'*'8"-m #*m m !-+-m +<2-"-m .0m "#100-**0m .0-"3!2-1m !-+#0!'*'8 *#1Ym 12#m #1m #*m !1-m "#m ,#O #)-#(-m ^&22.[ii555Y0!"' '-Y!-+i_Zm 3,m #+.0#1m ,-02#+#0'!,m /3#m &m '1*"-m +#"',2#mm3,m2-+2#m+32,2#m"#m$032-m"#m*0%m4'"Zm!.8m"#m!-,1#0401#m #,mA.2'+1m!-,"'!'-,#1m"30,2#m+3!&-1m+91m">1m/3#m3,m2-+2#m,-0+*Zm7m3,m2'.-m "#m20'%-m.2-m.0m!#*>!-1m^&22.[ii555Y0!"' '-Y!-+i!#*'!1$#5&#2_Ym',*+#,2#m +#,!'-,0m *m 1#m "#m "2-1m "#m 1-(m ^&22.[ii555Y1-7 #,2'**',%Y-0%i',"#6Y(1._m 0#*'8"m.-0m#*m"#.02+#,2-m"#m%#,A+'!m"#m.*,21m"#m*m,'4#01'""m"#m**',-'1m ^)/.",(O &&#()#-O (#0,-#.3O .O ,)(&_m *m !3*m #1m 3,m .*2$-0+m "#m m #$'!'#,2#m .-0m 131m *21m 211m "#m +32!'A,m 7m .-0m -$0#!#0m *m .-1' '*'""m "#m 31!0m +32,2#1m#,m$3,!'A,m"#m3,m$#,-2'.-m"#2#0+',"-m-m"#m3,m%#,m"#m',2#0<1m^--.#0m7m !-*YZm HFFN_Ym ,m *%3,1m .- *!'-,#1m 1#m &,m .-"'"-m '"#,2'$'!0m +32!'-,#1m /3#m &,m .0-.-0!'-,"-m3,m,3#4-m$#,-2'.-Ym-0m#(#+.*-Zm#,m2-+2#m*m+32!'A,mGJNKm#,m#*m %#,m >;m .0-4-!m 3,m !+ '-m #,m #*m -*&##(!m "#*m %#,m .0-.-0!'-,,"-m 3,m +m ',!-+.*#2-m "#m +-"-m /3#m *m .0-2#>,m ,-m .3#"#m 1',2#2'801#m !-00#!2+#,2#Ym 12m JJ O (.,)/#9(O +32!'A,m!-,$'#0#m0#1'12#,!'mm"-1m.-2'4'031[m*m4'031mm"#m*m.22m^)..)O#,/-OZm _m7m*m4'031m"#*m+-2#"-m"#*m.'+'#,2-m^**,O')..&O0#,/-Zm#_m^'0-,ZmHFGF_Ymm ,m +#*A,m *m 2<!,'!m ,-m 1-*-m &m .-"'"-m .0-.-0!'-,0m +32,2#1m $#,-2>.'!-1m ^&+,'j0"1Zm HFGF\m -,8*#8j-m 7m !-*YZm HFGG_m 1',-m /3#m "#+91Zm 1#m &m .-"'"-m 32'*'80m.0m!-,$'0+0m*m$3,!'A,m"#m*%3,-1m%#,#1Ym,m#(#+.*-m#1m*m!-,$'0+!'A,m "#m*m$3,!'A,m"#*m%#,mGm^02',m7m!-*YZmHFFO_Ym#m1#*#!!'-,0-,m20#1m',"'4'"3-1m +32,2#1m .0m #12#m %#,m "#,20-m "#m *m .- *!'A,m "#m Ym 1m +32!'-,#1m ^#0IFL&#Zm*7HJH0%m7m&#GOI#3_m #,m&-+-!'%-1'1m.0-"3!>,m*m$#+','8!'A,m"#m *1m $*-0#1m #,m 2-"m *m .*,2m 7m .-0m *-m 2,2-Zm *m !-,4#01'A,m "#m .*,21m +-,-'!1m m %',-'!1m^02',m7m!-*YZmHFFO_Ym 30,2#m *-1m B*2'+-1m @-1m &,m .0#!'"-m #123"'-1m +#2-"-*A%'!-1m /3#m &,m .#0+'2'"-m .#0$#!!'-,0m *m 2<!,'!m 7m -.2'+'80*Ym ,m "#m #121m ,3#41m +#2-"-*-%>1m #1m*m**+"mm^/&#O#O2.,.#)(O ,)'O,,3O#--/O ),O_Zm/3#m &m-.2'+'8"-m#*m+-"-m"#m.0#.0!'A,m"#m*1m+#8!*1m"#mYm,m*m2<!,'!m!*91'!m 1#m +#8!* ,m *-1m 1m #620>"-1m m .02'0m "#m *m %#,#0!'A,m HYm ,m !+ '-Zm #12m ,3#4m 2<!,'!m +#8!*m "'0#!2+#,2#m *-1m !-2'*#"-,#1m "#m .*,21m HYm "#+91Zm *m .0#.0!'A,m"#m*1m.*!1m"#m+#8!*m#1m"'12',2Ym#m"#,-+',mb.--*m#,mHcm7m!-,1'12#m #,m0#*'80m"-1m2'.-1m"#m.*!1m"#m+#8!*[m3,1m 1"1m#,m*m+#8!*1m"#m*-1m1m "#m*1m$'*1m"#m*1m.*!1m"#m*m.- *!'A,m7m*1m-201m!-,m*1m+#8!*1m"#m*-1m1m"#m *1m!-*3+,1m"#m*1m.*!1m"#m*m.- *!'A,Ymm4#,2(m#1m/3#m3,m4#8m"#2#!2"-m3,m +32,2#m,-m&!#m$*2m&!#0m*m"#!-,4-*3!'A,m7m/3#m!-,m#12m2#!,-*-%>m1#m!-,$'0+m "'0#!2+#,2#m*m$+'*'m+32"m#,m!3#12'A,m^0##*)1&+'m7m!-*YZmHFFO_Ym 20m0#!'#,2#m.3 *'!!'A,m-.2'+'8m2-"4>m+91m#*m.0-2-!-*-m!*91'!-[m'm^31&m 7m071,ZmHFGF_Ym,m#12#m+<2-"-m#*m.0-!#1-m.0m- 2#,#0m*m%#,#0!'A,mHm#1m"'12',2-Ym #1.3<1m "#m 32-.-*','80m *m %#,#0!'A,m Gm 7m !0#!#0*Zm 1#m 0#!-%#,m *1m 1#+'**1m HYm ',m #+ 0%-Zm #,m #12#m !1-m 1#m +#8!*,m *1m 1#+'**1m 7m .-12#0'-0+#,2#m 1#m &!#,m %#0+',0m "'0#!2+#,2#m #,m .*!1m N*O I071,Zm HFFJ\m *0)m 7m 071,Zm HFFM_Ym 0!'1m m #12#m 2'.-m "#m .*!1Zm 3,m 4#8m %#0+',"1m *1m .*,21m 7m .0#!'"1m *1m .0'+#01m&-(1m1#m.3#"#m0#*'80m*m#620!!'A,m"'0#!2+#,2#m#,m.*!Ymm"#2#!!'A,m"#m +32,2#1m 1#m &!#m +#"',2#m *m 2#!,-*-%>m "#m ,9*'1'1m "#m *m !304m "#m "'1-!'!'A,m ^_Ym 12-1m !+ '-1m .#0+'2#,m 0#"3!'0m #*m 2'#+.-m "#m #1.#0m .0m 0#*'80m *m "#2#!!'A,m"#m+32,2#1m7Zmm*m4#8Zm.#0+'2#,m1#*#!!'-,0m*1m.*,21m+32,2#1m,2#1m"#m 1#0m 201*""1m *m ',4#0,"#0-m !-,m *-m /3#m 1#m 0#"3!#m !-,1'"#0 *#+#,2#m #*m !-12#m "#*m #6.#0'+#,2-m^31&m7m071,ZmHFGF_Ymm m JK (.,)/#9( Genes candidatos para el TILLINGO m m BMFT T T T T T T T T TTT m m#*#!!'A,m"#*m%#,m"',m.0m#*m,9*'1'1m7m.-0m*-m2,2-Zm*m"#2#!!'A,m"#m+32,2#1m#,m3,m .*2$-0+m"#mm"#.#,"#m"#*m- (#2'4-m"#m*m',4#12'%!'A,m/3#m1#m#12<m0#*'8,"-Ym 0m#12#m20 (-m*m#*#!!'A,m"#m*-1m%#,#1m&m1'"-Zm.-0m3,m*"-Zm!-+.0- 0m*m#$'!'#,!'m"#m *m .*2$-0+m 32'*'8,"-m #*m %#,m '2-#,-m "#12301m ^_m 7Zm .-0m -20-m *"-Zm .-"#0m "#2#!20m+32,2#1m#,m%#,#1m"#m',2#0<1m%0-,A+'!-m!-+-m#1m#*m!1-m"#m;m0#*!'-,"-m !-,m*m+"30!'A,m"#*m$032-m7m"#m*-1m$!2-0#1m"#m','!'!'A,m"#m*m20"3!!'A,mJ[m>O7m 13m '1-$-0+m I#-)J>m ',4-*3!0"-1m #,m 0#1'12#,!'1m 0#!#1'41m m 4'031Ym ,m #*m 1'%3'#,2#m .02"-m 1#m .0#2#,"#m ',20-"3!'0m #12-1m %#,#1m 1>m !-+-m "0m *m ',$-0+!'A,m +-*#!3*0m 7m $3,!'-,*m /3#m 1#m 2'#,#m "#m #**-1m 7m .-"#0m #,2#,"#0m 13m #*#!!'A,m .0m #*m ,9*'1'1m +#"',2#m m#,m#12m2#1'1m"-!2-0*Ym T BMFMBTTP(2.$-.T$1 230 1 QT mm#1m3,m#,8'+m!*4#m.0m*m.0-"3!!'A,m"#m!0-2#,-'"#1m^'3*',-m7m!-*YZmGOOI\mm 'm7m!-*YZmGOOL\m1!1-,m7m!-*YZmHFFH_Ym-1m!0-2#,-'"#1m1-,m.'%+#,2-1m-0%9,'!-1m/3#m1#m #,!3#,20,m #,m .*,21m 7m -20-1m -0%,'1+-1m $-2-1',2<2'!-1Ym *m !-*-0m "#m #12-1m .'%+#,2-1m .3#"#m40'0m"#1"#m#*m+0'**-m&12m#*m0-(-m.1,"-m.-0m3,m%0,m40'#""m"#m,0,(1Ym *m!-*-0m#1m.0-4-!"-m.-0m13m#1203!230m+-*#!3*0m!-+.3#12m.-0m40'-1m"- *#1m#,*!#1m "#m!0 -,-m/3#m.0-"3!#,m#*m.0-!#1-m"#,-+',"-m!-,(3%!'A,m^'3*',-ZmGOOI_Ym30,2#m #12#m.0-!#1-m3+#,2,m*-1m"- *#1m#,*!#1m7Zm.-0m*-m2,2-Zm2+ '<,m3+#,2m*m*-,%'23"m "#m -,"m m *m /3#m .#0!' #m *m *38m *m +-*<!3*Zm ","-m !"m 4#8m 3,m !-*-0m +91m 0-('8-Ym -1m !0-2#,-'"#1m 2'#,#,m 40'1m $3,!'-,#1m "#.#,"'#,"-m "#*m -0%9,3*-m "A,"#m #12<,m !3+3*"-1m^',"#,m7m!-*YZmGOOG_Ym,m#*m!*-0-.*12-Zm*-1m!0-2#,-'"#1m 1-0 #,m*m*38m#,m #*m#1.#!20-m83*m^#,20#mJFFm7mLFFm,+_m7m*m#,#0%>m/3#m0#!' #,m*m20,1$'#0#,mm*m!*-0-$'*m ^'m 7m !-*YZm GOOL_Ym 1'+'1+-Zm *-1m !0-2#,-'"#1m 1-,m .0-2#!2-0#1m "#m *m -6'"!'A,m #,m *-1m .0-!#1-1m$-2-0#!2'4-1m#,m-0%,'1+-1m$-2-1',2<2'!-1m^'3*',-ZmGOOI\m02*#7m7m!-*YZmGOOO_Ym ,m *-1m !0-+-.*12-1Zm "-,"#m *m !*-0-$'*m ,-m #129m .0#1#,2#Zm 1#m !3+3*,m #,m 2#('"-1m !-+-m *-1m .<2*-1m "#m *1m $*-0#1m -m *-1m $032-1m #,m #12"'-1m 4,8"-1m "#100-**,"-m 3,m $3,!'A,m 91'!+#,2#m #1203!230*m 7m "#m 20!!'A,m .0m *m .-*','8!'A,m ^0-2#5-*"Zm HFFL_Ym m ',4#12'%!'A,m !-,m !*-0-.*12-1m "#m .*,21m 13.#0'-0#1m &m 73""-m m !-,-!#0m !-,m +91m "#2**#m *m *-!*'8!'A,m "#m *m Ym ,m #).#(O./'O1#m .3"-m *-!*'80m *m m #,m 3,m JLm (.,)/#9( Genes candidatos para el TILLING MKPm #,m *1m +#+ 0,1m "#m 2'*!-'"#1Ym ,m .-0!#,2(#m +3!&-m +#,-0m $3#m "#2#!2"-m 2,2-m #,m*m+#+ 0,m#62#0,m^KP_m!-+-m#,m#*m#120-+m^GLP_m^',"#,m7m!-*YZmGOOG\m*j '*'m7m 023,%Zm GOOO_Ym m 0#%3*!'A,m "#m #12m #,8'+m &m 1'"-m ',4#12'%"m #,m "'12',21m .*,21m !-+-m#*m,0!'1-m^*j '*'m7m023,%ZmGOOO_m7m#*m2-+2#m^#!)#0m7m!-*YZmGOOH\m'3*',-m7m !-*YZm GOOI_Ym m !-,!#,20!'A,m "#m !0-2#,-'"#1m 1>m !-+-m *m #6.0#1'A,m "#m *m m 7m *m '2-#,-m ',21m ^_m 3+#,2,m #,m !-,"'!'-,#1m "#m ',2#,1'""m "#m *38m #,m .*9,23*1Zm 1',m #+ 0%-Zm #*m 3+#,2-m #,m .*,21m "3*21m ,-m .0#!#m 1'%,'$'!2'4-Ym ,m *m 0>8Zm #121m !-,!#,20!'-,#1m "'1+',37#,m !-,1'"#0 *#+#,2#m +'#,201m /3#m #,m $*-0#1m 3+#,2,m #,m .<2*-1m7m,2#01m7m"'1+',37#,m#,m1<.*-1m7m!0.#*-1Ym30,2#m#*m"#100-**-m"#m*m$*-0m*m #6.0#1'A,m "#m + 1m #,8'+1m 3+#,2m "'#8m 4#!#1m ',+#"'2+#,2#m ,2#1m "#m *m ,2#1'1m ^'3*',-m7m!-*YZmGOOI_Ymm m '-1>,2#1'1m"#m!0-2#,-1m^'%30mGYM_m1#m','!'m!-,m20#1m!-,"#,1!'-,#1m0#*'8"1m.-0m *m #0,'*%#0,'*j'$-1$2-m 1',21m - 2#,'#,"-m #0,'*%#0,'*j'$-1$2-m ^_Ym -12#0'-0+#,2#m*m#,8'+m'2-#,-m1',21m^_m!2*'8m*m0#!!'A,m"#mmm$'2-#,-Ym 3#%-Zm 3,m 1#0'#m "#m "#1230!'-,#1m !-,4'#02#,m #*m $'2-#,-m #,m *'!-.#,-Ym -1m .0-"3!2-1m ',2#0+#"'-1m 2'#,#,m 3,m 0,%-m "#m !-*-0#1m !0!2#0>12'!-m "#m *-1m !0-2#,-1Zm "#*m 0-(-m "#*m *'!-.#,-m&12m#*m+0'**-m"#m*m8#6,2',m^'3*',-m7m!-*YZmGOOI_m^'%30mGYM_Ym m T m (&30 T BMH[m 32m "#m 1>,2#1'1m "#m !0-2#,-1m #,m .*,21Ym m .02'0m "#*m #0,'*%#0,'*j'$-1$2-m ^_m &12m *m - 2#,!'A,m"#m*32#>,m7m8#6,2',Zm.1,"-m.-0m*m$-0+!'A,m"#m*'!-.#,-m^$'%30m20"3!'"m7m".2"mm.02'0m JMm (.,)/#9( Genes candidatos para el TILLINGO "#m*m-0'%',*m"#m!&#*mYm)#*2-,m^)#*2-,m7m!-*YZmHFFL__Ym m m !-,4#01'A,m "#m $'2-#,-m m *'!-.#,-m 4'#,#m +#"'"m #,m %0,m .0-.-0!'A,m .-0m *m Ym 'm #12m #,8'+m ,-m $3,!'-,m !-00#!2+#,2#m -m ,-m #129m .0#1#,2#Zm *m 1>,2#1'1m "#m !0-2#,-1m 1#m "#2'#,#m .-0m !-+.*#2-m ^'01!& #0%m Zm HFFG_Ym m 31#,!'m "#m #12-1m .0-"3!2-1m &!#m /3#m #*m 2#('"-m,-m2#,%m.'%+#,2!'A,m*%3,m","-m!-+-m0#13*2"-m3,m.*,2m* ',Ymm4>m"#m !0-2#,-1m .0-1'%3#m #,m *m $-0+!'A,m "#m 6,2-$'*1Ym 121m 1-,m *1m .0#!301-01m "#m *m &-0+-,m"#m!0#!'+'#,2-m7m"#100-**-m"#m*m.*,2Zm#*m9!'"-m !>1'!-Ym-0m!-,1'%3'#,2#Zm*m ',2#003.!'A,m "#m *m #6.0#1'A,m "#m *m m 2+ '<,m .3#"#m .0-.-0!'-,0m $#,-2'.-1m #,,-1m ^',m7m!-*YZmHFFM_Ymm ,m0#13+#,Zm3,m+32,2#m2-2*m-m.0!'*m#,m#12#m%#,m.3#"#m.0-4-!0m$#,-2'.-1m$9!'*+#,2#m "#2#!2 *#1m 1',m ,#!#1'""m "#m &!#0m 3,m !0!2#0'8!'A,m -m #,17-1m #6&312'4-1m m ,'4#*m +#2 A*'!-m-m '-/3>+'!-Ymm4'13*'8!'A,m"#m#12-1m$#,-2'.-1m0#13*2m3,m!-,20-*m.0#!'1-m 7m09.'"-m.0m#6.#0'+#,2-1m!-+-m.-0m#(#+.*-m"#m20,1$-0+!'A,m-m"#m1'*#,!'+'#,2-m"#m %#,#1m ^&#,%Zm HFGF_Ym ,m *%3,-1m #123"'-1m .0#4'-1m !-,m +32,2#1m "#m *m m 1#m & >,m - 2#,'"-m .*,21m "#m ,#)*-#-m * ',1m 7m #,,1m ^',m 7m !-*YZm HFFM_m +#"',2#m #*m 1'*#,!'+'#,2-m -m *m +32!'A,m "'0'%'"m .-0m jYm #!'#,2#+#,2#Zm #,m 2-+2#m 1#m &m 1'*#,!'"-m *m m +#"',2#m m - 1#04,"-m 2+ '<,m 3,m "'1+',3!'A,m "#m *m .'%+#,2!'A,m #,m &-(1m +'#,201m /3#m #*m 1'*#,!'+'#,2-m "#m m ,-m &m $#!2"-m m *m .'%+#,2!'A,m#,m#*m$032-m^3"0,m7m!-*YZmHFGG_Ym -0m#12#m+-2'4-m*mm0#13*2m3,m 3#,m!,"'"2-m.0m*m!-+.0- !'A,m"#m*m#$'!'#,!'m "#m+32!'A,m"#m3,m.- *!'A,m"#mYm0!'1mm*m1#!3#,!'!'A,m"#*m%#,-+m"#*m +#*A,m ^0!'j1m 7m !-*YZm HFGH_m 1#m &m "#2#0+',"-m /3#m #12m #1.#!'#m 1A*-m .0#1#,2m 3,m !-.'m"#*m%#,m"#m*mZm"2-m0#*#4,2#m.0m#*m.0#1#,2#m#123"'-m"#mY T BMFMCT!TPTTTTTTEQT7T"#!T 1m .*,21m #129,m #,m !-,2!2-m !-,12,2#m !-,m -20-1m -0%,'1+-1m #6.-,'<,"-1#m m ',$#!!'-,#1[m 2/3#1m "#m ',1#!2-1Zm &-,%-1Zm !2#0'1m 7m 4'031Zm #,20#m -20-1m .2A%#,-1Ym m ',2#0!!'A,m #,20#m 3,m .*,2m 7m 3,m +'!0--0%,'1+-m .3#"#m 1#0m "#m 40'-1m 2'.-1m ^##,Zm GOOF_Zm "#1"#m 0#*!'-,#1m .01'20'1m ^0##, #0%m 7m -Zm HFFJ_m &12m 1'+ 'A2'!1m ^A.#8j 9#8m 7m !-*YZm HFGF\m #0,9,"#8j.0'!'-Zm HFGF_Ym -+-m 0#13*2"-m "#m #12m !-,12,2#m ',2#0!!'A,Zm *1m .*,21m &,m '"-m "#100-**"-m +#!,'1+-1m "#m "#$#,1m !-,12'232'4-1m #m ',"3!' *#1m ^##,Zm GOOF_Ym -+-m #(#+.*-m "#m *m "#$#,1m !-,12'232'4Zm .-"#+-1m !'20m *1m !0!2#0>12'!1m $>1'!-j/3>+'!1m "#m *m .0#"m !#*3*0m ^#,,7Zm GOOK_Ym ',m #+ 0%-Zm #6'12#m -20-m +#!,'1+-m "#m "#$#,1m +91m !-+.*#(-m #m ',"3!' *#m 1"-m #,m *m 1>,2#1'1m "#m !-+.3#12-1m /3>+'!-1m ^#,,7Zm GOOK_Ym 0m *m "#1!0'.!'A,m "#m #12#m 2'.-m "#m "#$#,1m 1#m &m JNm (.,)/#9( Genes candidatos para el TILLING 13%#0'"-m *m #6'12#,!'m "#m 3,m +#!,'1+-m .-0m .02#m "#m *m .*,2m 1"-m #,m 0#!#.2-0#1m !.!#1m"#m0#!-,-!#0m*m',$#!!'A,m7m!2'40m#*m1'12#+m"#m"#$#,1Ymm Ym *-0m ^*-0Zm GOMG_m +#"',2#m #123"'-1m #,20#m *m ',2#0!!'A,m "#*m *',-m !3*2'4"-m ^#(/'O /-#..#--#'/'Jm7m#*m&-,%-m&'*-),O&#(#m"#100-**Am*m2#-0>m"#*m%#,jj%#,m^'%30mGYN_Ym ,m#12m2#-0>m1#m#4'"#,!' m*m#6'12#,!'m"#m%#,#1m#,m*m.*,2m/3#m!-,$'#0#,m0#1'12#,!'m m 3,m .2A%#,-m #1.#!>$'!-Ym !23*+#,2#Zm 1#m 1 #m /3#m *1m 0#1'12#,!'1m #,m .*,21m .3#"#,m #120m%#,#0"1m.-0m3,m1A*-m%#,m^0#1'12#,!'m+-,-%<,'!_m-m.-0m#*m#$#!2-m"#m40'-1m%#,#1m ^0#1'12#,!'m .-*'%<,'!_Ym -12#0'-0+#,2#m 1#m &m .0-.3#12-m /3#m *-1m ',"3!2-0#1m "#m *m ',$#!!'A,m 1-,m %#,#1m **+"-1m 0,m ^$!2-0#1m "#m 4'03*#,!'_m .0#1#,2#1m #,m #*m .2A%#,-Zm "9,"-*#m m *m &'.A2#1'1m "#m *-0m 3,m $3,"+#,2-m %#,<2'!-m ^0)#0m 7m -*#+,Zm GOOM_Ym -1m %#,#1m0,m"#*m.2A%#,-m1#0>,m!.!#1m"#m',"3!'0m3,m0#1.3#12m"#m"#$#,1m#,m/3#**-1m &3<1.#"#1m/3#m!-,2#,%,m*-1m%#,#1m"#m0#1'12#,!'m#1.#!>$'!-1m^_m7m/3#m0#!-,-!#,m*m%#,m 0,O^0)#0m7m-*#+,ZmGOOM_Ym'm#12m',2#0!!'A,m,-m1#m.3#"#m"0m.-0m*2#0!'A,m"#m3,-m "#m*-1m"-1m%#,#1m^m-m0,_m#,2-,!#1m*m.*,2m0#13*2m',$#!2"Ym3,/3#m#*m+-"#*-m$3#m "#100-**"-m .0m *m ',2#0!!'A,m &-,%-j.*,2Zm 2+ '<,m &m 1'"-m 49*'"-m .0m #*m #,2#,"'+'#,2-m "#m -201m ',2#0!!'-,#1m $0#,2#m m -20-1m .2A%#,-1m !-+-m !2#0'1Zm 4'031Zm ,#+92-"-1m-m',1#!2-1m^##,ZmGOOF_m m m m m m TTTTTTTTTTT+ -2 TTTTT 2>&$-.T R T T 0RT 00T #1'12#,2#m 31!#.2' *#m 31!#.2' *#m 31!#.2' *#m m (&30 T BMIOT #.0#1#,2!'A,m "#*m 1'12#+m "#m 0#1'12#,!'m #,m .*,21m 1"-m #,m *m ',2#0!!'A,m %#,jj%#,m ^*-0Zm GOMG_Ym ,m *m 2 *m 13.#0'-0m 1#m 0#.0#1#,2m *m ',2#0!!'A,m #,m 1#m %#,<2'!Ym 0m 1'+.*'$'!0Zm 13.-,#+-1m /3#m *m JOm (.,)/#9( Genes candidatos para el TILLINGO .*,2m!-,2'#,#m#*m%#,m"#m0#1'12#,!'mm+'#,201m/3#Zm.-0m#*m!-,200'-Zm#*m%#,-2'.-m,m1'%,'$'!m/3#m*m.*,2m,-m 2'#,#m*m0#1'12#,!'Ym#m'%3*m+-"-m#*m.2A%#,-m#1m.-02"-0m"#m*m4'03*#,!'m^_m+'#,201m/3#m#*m%#,-2'.-mm,-m #1m!.8m"#m',2#0!!'-,0m!-,mYm m !23*+#,2#m1#m32'*'8m#*m2<0+',-m4'03*#,2-m.0m/3#**-1m.2A%#,-1m/3#m1-,m!.!#1m"#m ',$#!20m*m&3<1.#"m+'#,201m/3#m*-1m/3#m,-m2'#,#,m<6'2-m1#m"#,-+',,m4'03*#,2-1Ym-,m #121m 1#1m 1#m "#1!0' 'Am 3,m +-"#*-m "-,"#m 1#m .-">,m "0m ',$#!!'-,#1m !-+.2' *#1m #m ',!-+.2' *#1m ^,m "#*m *,)m 7m !-*YZm GOLK_Ym ,m ',$#!!'A,m !-+.2' *#m !-,1'12#m #,m *m ',2#0!!'A,m #,20#m 3,m .2A%#,-m 4'03*#,2-m 7m 3,m &3<1.#"m 131!#.2' *#Ym ,m ',$#!!'A,m ',!-+.2' *#m1#m"m#,20#m3,m.2A%#,-m4'03*#,2-m7m3,m&3<1.#"m0#1'12#,2#Zm"#m+-"-m/3#m 1'm#*m&3<1.#"m!-,2'#,#m#*m%#,m"#m0#1'12#,!'m!.8m"#m0#!-,-!#0m#*m$!2-0m"#m4'03*#,!'m "#*m.2A%#,-Zm"#1#,!"#,m3,m.0-!#1-m"#m1#@*'8!'A,m.0m*m!2'4!'A,m"#m*m0#1.3#12m "#m"#$#,1Ymm#12m0#1.3#12m1#m*m"#,-+',m0#1.3#12m"#m&'.#01#,1' '*'""m^_m^#,2Zm GOOL_Ym',m#+ 0%-Zm1'm*m.*,2m,-m!-,2'#,#m#*m!-+.*#(-mm!.8m"#m0#!-,-!#0m#*m$!2-0m 0,O#,2-,!#1m #*m .2A%#,-m ',$#!2m *m .*,2m ^02',m 7m !-*YZm HFFI_Zm 7m .-"#+-1m !-,1'"#00m #1#m$!2-0m"#m4'03*#,!'m!-+-m3,m$!2-0m4'03*#,2-Ymm -0m *-m 2,2-m *-1m %#,#1m m "#1#+.#@,m 3,m ..#*m $3,"+#,2*m #,m #*m 0#!-,-!'+'#,2-m "#*m %#,m 0,m 7m #,m !-,1#!3#,!'m #,m *m 0#1'12#,!'m "#m *m .*,2m $0#,2#m m .2A%#,-1Ym m 09.'"m #4-*3!'A,m"#m*1m.*,21m#,m#12#m1#,2'"-m&m**#4"-mm3,m%0,m"'4#01'$'!!'A,m"#m%#,#1mm ^&'1&-*+m 7m !-*YZm HFFL_Ym 12-1m 1#m &,m .-"'"-m !*1'$'!0m #,m $3,!'A,m "#m *-1m "-+','-1m #1203!230*#1m/3#m!-,2'#,#,m^#,2ZmGOOL\m,m-'(#,ZmHFFM_Ym#m&,m"#1!0'2-m!',!-m%03.-1[m *m!*1#mm/3#m!-+.0#,"#m*-1m%#,#1m"#m0#1'12#,!'m/3#m!-"'$'!,m.0m.0-2#>,1m!-,m*m +#,-1m 3,m "-+','-m #,m &<*'!#m 13.#0m #,0-**"Zm 3,m 1'2'-m "#m 3,'A,m m ,3!*#A2'"-1m 7m 3,m "-+','-m 0'!-m #,m 0#.#2'!'A,m "#m #3!',m ^#3_m ^jj_Ym m 1#%3,"m !*1#m m !-,2'#,#,m*m+#,-1m3,m"-+','-m"#m0#!#.2-0m2'.-m-**m7m*-1m-20-1m"-1m"-+','-1m'%3*#1mm *m !*1#m m ^jj_Ym m !*1#m m ^,*.),N&#%O *,).#(_m 2'#,#,m 3,m 0#!#.2-0m "#m /3',1m 1#0',j20#-,',m 7m 3,m "-+','-m #620!#*3*0m !-+.3#12-m .-0m 3,m 0#%'A,m 0'!m #,m 0#.#2'!'-,#1m"#m*#3!',m^#0i&0j_Ymm!*1#mm1-,m/3#**-1m%#,#1m!-,m3,m"-+','-m /3',1m7m3,m0#%'A,m#620!#*3*0m0'!m#,m0#.#2'!'-,#1m"#m*#3!',m^j',_Ym',*+#,2#Zm #*m B*2'+-m %03.-m ',!*37#m 2-"-1m /3#**-1m %#,#1m "#1!0'2-1m #,m /3#m 13m $3,!'-,+'#,2-m #1m m 204<1m "#m "'12',2-1m +#!,'1+-1m +-*#!3*0#1m !-+-m .-0m #(#+.*-m '&)m 7m -N;m ^31!&%#1Zm GOOM\m 0,"5%2Zm HFFH_Ym -1m %#,#1m m &,m 1'"-m '1*"-1m #,m 40'1m #1.#!'#1m "#m .*,21Zm +3!&-1m "#m #**-1m #,m *m $+'*'m "#m *1m 1-*,9!#1Zm "-,"#m 1#m &,m '1*"-m IIm %#,#1m "#m 0#1'12#,!'m^,m-'(#,ZmHFFM\m-+#0m7m!-*YZmHFFM_Ym',m#+ 0%-Zm2+ '<,m1#m&,m!*-,"-m +3!&-1m-20-1m#,m-201m#1.#!'#1m!-+-m#,m,#)*-#-O."&#(m^HGmj%#,#1_m^#7#01m7m!-*YZm KFm Genes candidatos para el TILLING (.,)/#9( GOOO_Zm,34O-.#0m^00-8ZmJmj%#,#1_m^-,%m7m!-*YZmGOOK_Zm//'#-O'&)m^Gmj%#,_m^ -- #30m 7m!-*YZmHFFJ_m7m./O-.#0m^*#!&3%ZmGmj%#,_m^&#,m7m!-*YZmHFFH_Ym -1m 4'031m 1-,m !.!#1m "#m "#100-**0m +#!,'1+-1m .0m 1#%300m 13m 13.#04'4#,!'m 7m 2'#,#,m *m !.!'""m "#m +320m 7m !-,1#%3'0m #4"'01#m "#m *-1m 1'12#+1m ',+3,'20'-1Ym !-123+ 0,mm!-,12'23'01#mm.02'0m"#m20#1m-m!320-m.0-2#>,1Ym12m*'+'2!'A,m*#1m- *'%Zm #,m+3!&1m-!1'-,#1Zmm32'*'80m*-1m0#!301-1m"#*m.0-.'-m&3<1.#"m.0m.-"#0m1- 0#4'4'0m7m &!#0m#$#!2'4m*m',$#!!'A,Ym01#0m^01#0ZmGONL_m.0-.31-m/3#m*m.<0"'"m"#m!-+.-,#,2#1m "#*m&3<1.#"m,#!#10'-1m.0m#*m!'!*-m"#m*m4'"m"#m*-1m4'031m.-">m1#0m2+ '<,m3,m2'.-m"#m 0#1'12#,!'Ym m #12m 0#1'12#,!'m 1#m *#m **+m 0#1'12#,!'m 0#!#1'4Ym 12m &'.A2#1'1m &m 1'"-m !-,$'0+"Zm 1- 0#2-"-Zm !-,m .0-2#>,1m 0#*!'-,"1m !-,m *m +/3',0'm "#m 20"3!!'A,m !#*3*0m^- %*'m7m0,2ZmHFFL_Ymm *%3,-1m 1'12#+1m "#m 0#1'12#,!'m 0#!#1'4m #,m .*,21m &,m 1'"-m "#1!3 '#02-1m 0#!'#,2#+#,2#Ym,m#(#+.*-m1-,m*-1m$!2-0#1m"#m','!'!'A,m"#m*m20"3!!'A,m7m#,m.02'!3*0m *m$+'*'m"#m.0-2#>,1m>m7m>O^'%30mGYO_m^'#2-m7m!-*YZmHFFLZm- %*'m7m0,2Zm HFFLZm03,'%#0ZmHFFN_Ym *m .0-!#1-m "#m 20"3!!'A,m "#m +m m .0-2#>,m !-,12m 91'!+#,2#m "#m 20#1m $1#1[m ','!'!'A,Zm#*-,%!'A,m7m2#0+',!'A,m^* #021m7m!-*YZmHFFL_Ymm$1#m"#m','!'!'A,m!-,1'12#m #,m *m ',2#0!!'A,m #,20#m *1m "-1m 13 3,'""#1m "#*m 0' -1-+m 7m #*m !-"A,m "#m ','!'-m "#*m +Ym30,2#m*m#*-,%!'A,m1#m"m*m1>,2#1'1m"#*m.<.2'"-m#,m$3,!'A,m"#m*m*#!230m"#m *-1m !-"-,#1m "#*m +#,1(#0-m "#,20-m "#*m 0' -1-+Ym ',*+#,2#Zm *m 2#0+',!'A,m '+.*'!m *m ',2#0!!'A,m "#*m 0' -1-+m !-,m #*m !-"A,m -.)*m 7m *m "'1-!'!'A,m !-+.*#2m "#*m +m 7m #*m !-+.*#(-m0' -1-+*Ymm KGm (.,)/#9( m Genes candidatos para el TILLINGO m (&30 TBMJ[m1/3#+m"#*m$3,!'-,+'#,2-m"#*m','!'-m"#m*m20"3!!'A,m"A,"#m*-1m$!2-0#1m"#m','!'!'A,m(3#%,m3,m ..#*m'+.-02,2#m#,m*m#12 '*'8!'A,m"#*m+m^$3#,2#[m#**'1m7m!-*YZmHFFH_Ym m ,m*m$1#m"#m','!'!'A,m"#m*m20"3!!'A,m!-,20' 37#,m3,m1#0'#m"#m$!2-0#1m#3!0'-21m"#m ','!'!'A,m"#m*m20"3!!'A,m^_Ym,'!'*+#,2#m*m13 3,'""m0' -1A+'!mJF1m1#m!#0!m*mKam "#*m +Ym #1.3<1Zm 3,m +-4'+'#,2-m *2#0*m -m -((#(!m !-,"3!#m *m 0#!-,-!'+'#,2-m "#*m .0'+#0m !-"A,m m ^#*m !-"A,m ','!'"-0m "#m *m 20"3!!'A,_Ym -12#0'-0+#,2#m 1#m "m *m $-0+!'A,m"#m*m13 3,'""m0' -1A+'!mLFm7m*m$1#m"#m#*-,%!'A,Ym*m$!2-0m>O3,#m*m .02#m Kam !-,m *m .02#m Iam "#*m +Ym *m !-+.*#(-m >m #129m !-+.3#12-m .-0m "-1m 13 3,'""#1[m >m 7m "-1m .0-2#>,1m +91[O >m 7m >Ym m .0-2#>,m #Jm 1#m 3,#m *m #620#+-mKam"#*m+mm204<1m"#m3,m.0-2#>,m"#m3,'A,mm^)&3OO#(#(!O,).#(_m ^'%30mGYO_Ym-0m-20-m*"-Zm>m#1m3,m!-+.*#(-m"#m.0-2#>,1m/3#m2'#,#m*m!.!'""m"#m ',2#0!!'-,0m !-,m -201m 0#%'-,#1m "#*m 1'12#+m "#m ','!'!'A,m "#m *m 20"3!!'A,m !-+-m .-0m #(#+.*-m#*m#620#+-m.-*'mm^m204<1m"#m*m.0-2#>,m_m-m!-,m#*m$!2-0m>O^&#*'!1m /3#m"#1#,0#"m#1203!2301m1#!3,"0'1_m7m2+ '<,m!-,m#*m$!2-0m=O^!-+.*#(-m"#m40'1m 13 3,'""#1m/3#m',2#0!!'-,m!-,m*m13 3,'""m0' -1A+'!mJF_m^#**'1m7m!-*YZmHFFH_Ym KHm Genes candidatos para el TILLING (.,)/#9( 1m$3,!'-,#1m"#m#12-1m"-1m$!2-0#1m^>O7m>_m1-,m 91'!+#,2#m',2#0!!'-,0m!-,m#*m +m 7m "'0'%'0*-m "#m +-"-m /3#m #*m 0#12-m "#m .0-2#>,1m .3#",m !230m 1- 0#m <*Ym 1>m .-0m #(#+.*-m>m3,'"-mmm1#m#,!0%m"#m',2#0!!'-,0m!-,m#*m#620#+-mIam.0m.#0+'2'0m *m 0#!'0!3*0'8!'A,m 1- 0#m 1'm +'1+-m "#*m +m +'#,201m /3#m *m .0-2#>,m >m ',2#0!!'-,m!-,m#*m#620#+-mKam^- %*'m7m0,2ZmHFFL_Ym 91m"#m*m+'2"m"#m*-1m%#,#1m,230*#1m"#m0#1'12#,!'mm.-2'4'031m#,m.*,21m1#m 1,m#,m 3,m +#!,'1+-m "#m 0#1'12#,!'m 0#!#1'4m +'#,201m /3#m #,m -20-1m 2'.-1m "#m 4'031m 1A*-m 1#m #,!3#,20m #12#m 2'.-m "#m 0#1'12#,!'m #,m 3,m HFPm ^0-44'"#,2'm 7m +.2-,Zm GOOH_Ym -1m .-2'4'031m 1-,m 4'031m "#m !"#,m 1'+.*#m .-1'2'4m "#m +Ym 12,m !-+.3#12-1m .-0m 3,m .0-2#>,m 4'0*m ^%_m #,m #*m #620#+-m KaZm 3,m !"#,m "#m .-*'"#,',1m #,m #*m #620#+-m Iam 7m -201m.0-2#>,1m4'0*#1m/3#m"#1.3<1m"#m*m',$#!!'A,m.1,mm1#0m$3,!'-,*#1m+#"',2#m*1m .0-2#11m4'0*#1Ymm.0-2#>,m%m#1m*m!*4#m.0m*m',2#0!!'A,m!-,m#*m$!2-0m>Zm-m13m '1-$-0+mI#-)J>Zm2*m7m!-+-m1#m&m"#+-120"-m#,m#6.#0'+#,2-1m"#m"- *#m&> 0'"-m#,m *#4"301m ^'22+,,Zm 7m !-*YZm GOOM_Ym "#+91m -20-1m #123"'-1m +91m .0#!'1-1m "#$',#,m /3#m +32!'-,#1m #,m *m .0-2#>,m %m '+.'"#,m *m ',2#0!!'A,m !-,m #*m $!2-0m I#-)J>m 7Zm .-0m *-m 2,2-Zm *m ',!.!'""m "#m ',$#!20m .-0m .02#m "#*m 4'031m ^<-,0"m 7m !-*YZm HFFF_Ym #m &m "#+-120"-m 2+ '<,Zm /3#m +32,2#1m #,m #*m %#,m I#-)J>m .0-"3!'"-1m +#"',2#m m #,m ,#)*-#-m.'#0"#,m*m131!#.2' '*'""mmm^))O."O0#,/-_m^#**'1m7m!-*YZmHFFH_Ym #m&m.-"'"-m'1*0m*m%#,m>m!-+-m0#1.-,1 *#m"#m*%3,1m0#1'12#,!'1m,230*#1m#,m "'12',21m #1.#!'#1Ym *%3,-1m #(#+.*-1m 1-,m #*m %#,m ');m #,m *#!&3%m /3#m "m 0#1'12#,!'m *m 4'031m m ^../O ')-#O 0#,/-_m ^'!'1#m 7m !-*Zm HFFI_Zm #*m %#,m -';m #,m %3'1,2#m /3#m "m 0#1'12#,!'m m m ^O -N),(O ')-#O 0#,/-_m ^-m 7m !-*m Zm HFFJ_Zm #*m %#,m *).N;m #,m 2-+2#m /3#m "m 0#1'12#,!'m m m ^)..)O 0#,/-O _m ^3$$#*m 7m !-*Zm HFFK_m 7m $',*+#,2#m 2+ '<,m#,m+#*A,m#*m%#,m(-0m/3#m"m0#1'12#,!'m*m,')0#,/-mm^&)(O(,).#O-*).O 0#,/-_m^'#2-m7m!-*YZmHFFL_Ym-"-1m#**-1m1-,m&-+A*-%-1m"#m>m7m!-,2'#,#,m+32!'-,#1m #1.#!>$'!1m/3#m"#2#0+',,m*m0#1'12#,!'Ym-"1m*1m+32!'-,#1m"#1!0'21m#,m#12-1m%#,#1m #129,m *-!*'8"1m #,m 8-,1m ,-m !-,1#04"1m "#*m %#,Ym 0!'1m m *m .0#"'!!'A,m "#m *m #1203!230m Im 1#m &m .-"'"-m "#1!0' '0m *m *-!*'8!'A,m "#m *1m +32!'-,#1m !#0!m "#m *m .0-2#>,m"#m3,'A,m%.m"#*m+m-m '#,m#,m8-,1m#62#0,1m"#m#12m^- %*'m7m0,2Zm HFFL_Ym '#2-m 7m !-* -0"-0#1m #,m #*m HFFLm "#100-**0-,m 3,m 20 (-m #,m +#*A,m "-,"#m "#+-1200-,m +#"',2#m !*-,(#m .-1'!'-,*m 7m +'!0-1',2#,'m !-,m ,#)*-#-m /3#m #*m *-!31m "#*m%#,m(-0m/3#m" m0#1'12#,!'m*m4'031mm!-00#1.-,">m*m%#,m/3#m!-"'$'! m.-0m #*m $!2-0m "#m ','!'!'A,m "#m *m 20"3!!'A,m ^>_Ym -+.*#+#,20-,m #*m 20 (-m !-,m #6.#0'+#,2-1m"#m#6.0#1'A,m!-,$'0+,"-m/3#m#*m%#,m(-0m#0m>m7m"#+91m1#m'"#,2'$'!Am *m +32!'A,m 0#1.-,1 *#m "#m *m 0#1'12#,!'m m m /3#m .0-4-!4m 3,m !+ '-m #,m *m .-1'!'A,mHHNm^'1j#3_m"#m*m1#!3#,!'m.0-2#'!Ym20-m#123"'-m"#m!-Zm^'#2-m7m KIm (.,)/#9( Genes candidatos para el TILLINGO !-*YZmHFFM_m!-,$'0+Am/3#m*m+32!'A,m"#1!0'2m#1m*m/3#m!-,$#0>m0#1'12#,!'mmm#,m 40'1m "#m *1m 40'#""#1m ,*'8"1Ym -12#0'-0+#,2#Zm #12m ',$-0+!'A,m $3#m +.*'"m ',4#12'%,"-m #*m +#!,'1+-m .-0m #*m !3*m #*m $!2-0m >m 0#%3* m *m 0#1'12#,!'m m Ym -0m 3,m*"-m1#m+.Am*m0#%'A,m#,m#*mIam/3#m"#2#0+', m*m^_4'03*#,!'m+#"',2#m 4'031m /3'+<0'!-1m ^4'03*#,2-1m 7m 4'03*#,2-1_m 7m .-0m -20m .02#Zm 1#m '"#,2'$'!Am #*m $0%+#,2-m **+"-mIajm^*O(*((.O,(-&.#)(&O("(,_m#,m#*mIam!-+.0- ,"-m/3#m #0m "#!'1'4-m .0m *m 4'03*#,!'m "#*m 4'031Ym *m 4'031m ,-m .-">m ',$#!20m .-0/3#m ,-m 1#m " m 3,m!-00#!2m',2#0!!'A,m#,20#m#12m.02#m"#*mm4'0*m7m#*m!-+.*#(-m"#m','!'!'A,m"#m*m 20"3!!'A,m7m.-0m*-m2,2-Zm*m.*,2m0#13*2 m0#1'12#,2#m^03,'%#0m7m!-*YZmHFFN_Ymm ,m ,#)*-#-O 1#m !-,$'+Am /3#m I#-)J>m 7m >m 2'#,#,m 3,m JLPm "#m 1#+#(,8m #,m *m 1#!3#,!'m+',-!>"'!m^-"0>%3#8m7m!-*YZmGOON_Ym3,/3#m1#m&m"#+-120"-m/3#m+ 1m .0-2#>,1m1#m#,!3#,20,m#,m*m+'1+m!-,!#,20!'A,m^-"0>%3#8m7m!-*YZmGOON_m,-m1#m1 #m #6!2+#,2#m !A+-m $3,!'-,m #*m +#!,'1+-m +#"',2#m #*m !3*m 1#m "#!'"#m !39*m "#m *1m "-1m 1#09m *m 0#1.-,1 *#m "#m ',2#0!!'-,0m !-,m *m .0-2#>,m %m "#*m m 4'0*Ym ,m 1'"-m .0-.3#121m 20#1m .-1' *#1m $3,!'-,#1m .0m I#-)J>m ^'%30m GYGF_m %0!'1m *m #123"'-m #,m +32,2#1m!-,m.<0"'"m"#m131!#.2' '*'""m#,m,#)*-#-O^#**'1m7m!-*YZmHFFH_Ymm #1.#!2-m *m %#,O >m "# #m !-+#,201#m /3#m 7m 1#m &,m #,!-,20"-m +32,2#1m +#"',2#m m#,m2-+2#m7m!# "m^*+<m7m!-*YZmHFFN_Ym,m2-+2#m1#m'"#,2'$'!Am3,m+32,2#m /3#m.#0">m*m!.!'""m"#m-*&##(!m#,20#m#*m1#%3,"-m7m2#0!#0m#6A,m7m*m.0-2#>,m,-m.-">m #6.0#101#m!-00#!2+#,2#Ym#m!0!2#0'8Am*m',+3,'""m"#m#12#m+32,2#m#6.-,'<,"-*-mm "'12',2-1m4'031m"#+-1209,"-1#m/3#m#0m0#1'12#,2#mm"-1m"#m#**-1[m*m4'031mm"#m*m.22m ^)..)O #,/-O Zm _m 7m *m 4'031m "#*m +-2#"-m "#*m .'+'#,2-m ^**,O ')..&O 0#,/-Zm #_m ^'0-,m7m!-*YZmHFGF_Ymm 0!'1mm*m0#!'#,2#m.3 *'!!'A,m"#*m%#,-+m"#*m+#*A,m^0!'j1m7m!-*YZmHFGH_m1#m&m .-"'"-m !-+.0- 0m /3#m #6'12#m 1A*-m 3,m !-.'m "#*m %#,m >m 1>m !-+-m "#m 13m '1-$-0+m I#-)J>Ym O KJm Genes candidatos para el TILLING (.,)/#9( m m (&30 TBMBA[m3,!'-,#1m.-123*"1m.0m#*mI#-)J>YmQT,'!'"-0m"#m*m20"3!!'A,mm.-0m13m$3,!'A,m"#m3,'A,mm *m.0-2#>,m%m"#*m+m4'0*YmQm12 '*'8"-0m"#*m%#,-+Ymm3,'A,m#,20#mI#-)J>jm%m.3#"#m.0-2#%#0m *m +m 4'0*m "#m *m !!'A,m "#m .0-2#>,1m b"#!."-01cm !-+-m *m j*')#m -m #6-,3!*#11m /3#m "#%0",m #*m m !-+-m *m j*')#Ym Qm 09$'!-m ',20!#*3*0Ym I#-)J>Zm ',2#0!!'-,m !-,m I#-)J>m /3#m **#4m "&#0'"-1m +'!0-2B 3*-1m!-,m!2'4'""m"#m"&#1'A,Ym#m#12#m+-"-mI#-)J>m3,#m*1m.0-2#>,1m4'0*#1m!-,m-201m.0-2#>,1m !-,m!2'4'""m20,1.-02"-0m^$3#,2#[m#**'1m7m!-*YZmHFFH_Ym T BMFMDTTTTBTT *m #2'*#,-m ^HJ_m #1m 3,m &-0+-,m /3#m #,20#m -201m +3!&1m $3,!'-,#1m #,m .*,21m !2Bm !-+-m!2'4"-0m"#m*m+"30!'A,m"#m*-1m$032-1m!*'+2<0'!-1Ymm.0-"3!!'A,m"#m#2'*#,-m !-+.-02m 3,m !+ '-m #,m *m !-,1'12#,!'m "#*m $032-m ^03++#**m 7m 0.12#0Zm HFFG_Zm #,m #*m !-*-0m "#m *m .'#*m ^*-0#1m 7m !-*YZm HFFH_m 7m #,m *m .0-"3!!'A,m "#m 0-+1Zm #,20#m -20-1m #$#!2-1m ^#7+-30m7m!*11-,ZmGOOI_Ym 1>,2#1'1m"#m#2'*#,-m4'#,#m0#%3*"m.-0m3,m+#!,'1+-m "#m 0#20-*'+#,2!'A,m !-,12'23'"-m 91'!+#,2#m .-0m #*m !'!*-m "#m ,%m ^'%30m GYGG_m (3,2+#,2#m!-,m*m.0-"3!!'A,m"#m#2'*#,-mm.02'0m"#mm^j"#,-17*+#2&'-,',#_m7m"#m *m"'$31'A,m"#*m#2'*#,-mm204<1m"#*m$032-m^#,0"m7m-3 *#ZmHFFK_Ym#0-m*m0#%3*!'A,m"#*m #2'*#,-m .3#"#m 1#0m 2,2-m m ,'4#*m '-1',2<2'!-m !-+-m m ,'4#*m 0#!#.2'4-Ym #m !-,-!#m "#m *m !!'A,m *'+'2,2#m 1- 0#m *m .0-"3!!'A,m "#m #2'*#,-m "#m *%3,1m #,8'+1m !-+-m *m m -6'"1m 7m *m m 1',21m ^'%30m GYGG_Ym #0-m *m 0#%3*!'A,m m ,'4#*m "#m 0#!#.!'A,m #1m +91m KKm (.,)/#9( Genes candidatos para el TILLINGO "#1!-,-!'"Ym*m&#!&-m"#m/3#m#*m#2'*#,-m1A*-m!2B#m#,m2#('"-1m#1.#!>$'!-1m7m/3#m1#m3,m +-*<!3*m%1#-1m,-1m',"'!m/3#m13m0#!#.!'A,m#1m3,m.0-!#1-m!-+.*#(-Ym m m m (&30 TBMBB[m1/3#+m"#*m!'!*-m"#m,%m7m*m4>m"#mjmHJm&12m*m$-0+!'A,m"#m#2'*#,-Ym0'-1m$!2-0#1m #62#0,-1m0#%3*,m#,m.02#m*m1>,2#1'1m"#m#2'*#,-m7m1#mm,'4#*m.-1'2'4-m!-+-mm,'4#*m,#%2'4-m^$3#,2#[m- #0A,m7m !-*YZmHFFK_m m m 20'.*#m 0#1.3#12m *m #2'*#,-m 1#m 1m #,m 20#1m !+ '-1m +-0$-*A%'!-1m "30,2#m *m %#0+',!'A,m #,m !-,"'!'-,#1m "#m -1!30'""m 7m .0#1#,!'m "#m #2'*#,-[m &'.-!-2'*-1m 7m 0>!#1m +91m !-021m 7m $',1m 7m 3,m !0#!'+'#,2-m !0!2#0>12'!-m #,m $-0+m "#m %,!&-m ^*##!)#0Zm GOOO\m 38+,m 7m !)#0Zm GOOF_Ym ,m 1'"-m '"#,2'$'!"-1m 40'-1m +32,2#1m #,m ,#)*-#-O /3#m ,-m +3#120,m*m20'.*#m0#1.3#12m*m#2'*#,-m7m/3#m.-0m*-m2,2-Zm.0#1#,2,m',1#,1' '*'""mm#12m &-0+-,Ym*m'1*+'#,2-m"#m*-1m%#,#1m0#1.-,1 *#1m"#m#12-1m$#,-2'.-1m&,m1'"-m31"-1m .0m#,2#,"#0m#*m+#!,'1+-m"#m0#!#.!'A,m"#*m#2'*#,-m1>m!-+-m13m1#@*m"#m20,1"3!!'A,m ^&,%m 7m !-*YZm GOOI\m #&+,m 7m !-*Y\m GOOL_Ym ,-m "#m #12-1m %#,#1Zm /3#m !-"'$'!m .0m 3,m 0#!#.2-0m"#*m#2'*#,-Zm#1m#*m;Ymm KLm Genes candidatos para el TILLING (.,)/#9( *m ;m $-0+m .02#m "#m 3,m $+'*'m "#m %#,#1m /3#m #,m ,#)*-#-m #129m !-+.3#12m .-0m !',!-m 0#!#.2-0#1[m ;FO ;FO >FO <Zm 7m <m ^3m 7m !-*YZGOOK_Ym -"-1m #**-1m 1-,m 0#!#.2-0#1m "#*m #2'*#,-m 7Zm m *m 4#8Zm 0#%3*"-0#1m ,#%2'4-1m "#m <12#Ym ,m ,#)*-#-m 1#m &m "#+-120"-m /3#m +32,2#1m "#$'!'#,2#1m #,m #121m .0-2#>,1m 1-,m ',1#,1' *#1m *m #2'*#,-m '*)',1-,m 7m !-*YZm GOOK_Ym 1203!230*+#,2#m 2-"-1m 1-,m +37m 1'+'*0#1m 1'#,"-m .0-2#>,1m 20,1+#+ 0,*#1m 3,/3#m #,m #*m !1-m "#m ;FO ;m 7m >m !-,2'#,#,m "#+91m 3,m "-+','-m 0#!#.2-0m j2#0+',*m m !-,2',3!'A,m "#*m "-+','-m '12'"',m /3',1m ^&#,m 7m **'#ZmHFGF_Ym m .0-2#>,m ;m !-,2'#,#m 3,m 0#%'A,m "#m *2m $','""m 7m "#m 3,'A,m *m #2'*#,-m ^'%30m GYGH_Ym,m,#)*-#-m#1m3,m">+#0-m"#mHm.0-2#>,1m',2#%0*#1m"#m+#+ 0,m!-,m!2'4'""m &'12'"',m)',1m7m!.!'""m32-$-1$-0'*,2#Ymm3,'A,m"#*m#2'*#,-mm13m0#!#.2-0m',"3!#m 13m 32-$-1$-0'*!'A,m m ,'4#*m "#m 0#1'"3-1m "#m &'12'"',m 7m *3#%-m *m 20,1$#0#,!'m "#m #12-1m $-1$2-1m &!'m 0#1'"3-1m "#m 1.022-Ym *m 0#!#.2-0m 1>m !2'4"-m ','!'m 3,m !1!"m "#m 1#@*'8!'-,#1m &!'m -201m .0-2#>,1m #$#!2-01m ^!1!"m "#*m 2'.-m m /3',1m !-,m "#12',-m$',*mm,'4#*m"#*m_m^- #0A,m7m!-*YZmHFFK_m^'%30mGYGH_Ymm m m m (&30 TBMBC[m 1/3#+m "#*m ;m 7m "#*m +#!,'1+-m "#m 0#!#.!'A,m "#*m #2'*#,-m #,m ,#)*-#-Ym ^$3#,2#[m - #0A,m 7m !-*YZmHFFK_Ym m 6'12#,m +32!'-,#1m "#1!0'21m #,m ,#)*-#-m #,m #*m #620#+-m +',-m &'"0-$A '!-m /3#m 0#"3!#,m -m ,3*,m *m 3,'A,m *m #2'*#,-m ^!&**#0m 7m *##!)#0Zm GOOK_Ym 19,"-1#m #,m #121m .03# 1m40'-1m32-0#1m&,m!-,!*3'"-m/3#m#*m%#,m;m2'#,#m3,m!-+#2'"-m'+.-02,2#m#,m *m 0#!#.!'A,m "#*m #2'*#,-m ^#,m 7m !-*YZm GOOKZm &-,%m 7m !-*YZm HFFNZm 12%,m 7m !-*YZm HFFM_Ym 1'+'1+-Zm #,m ,#)*-#-m #129m "#1!0'2m *m +32!'A,m !-00#1.-,"'#,2#m *m +',-9!'"-m 71JK70m "#m *m 0#%'A,m j2#0+',*m /3#m .0-4-!m 3,m $#,-2'.-m !-,m 3,m ',2#,1m KMm (.,)/#9( Genes candidatos para el TILLINGO ',1#,1' '*'""m *m #2'*#,-m ^*##!)#0Zm GOOO_Ym -0m -20-m *"-Zm -20-1m #123"'-1m ^'!)m 7m 3*2#0Zm GOKL_m "#+-1200-,m /3#m #*m +32,2#m ,m ^0,O ,#*m _m "#m 2-+2#m 2#,>m $032-1m /3#m ,-m +"30 ,Ym&-0m1#m1 #m/3#m#12#m+32,2#m,m#1m',1#,1' *#m*m#2'*#,-m^,&,m7m!-*YZm GOOJ_m 7m /3#m #*m *-!31m /3#m .0-4-!m #*m $#,-2'.-m ,m 2'#,#m &-+-*-%>m !-,m #*m %#,m ;m "#m ,#)*-#-Em m +32!'A,m 0#1.-,1 *#m #,m 2-+2#m #1m 3,m !+ '-m "#m 1#m /3#m .0-4-!m 3,m !+ '-m+',-!>"'!-m"#m.0-*',mm*#3!',Ym12-1m,2#!#"#,2#1mm',"'!,m/3#m;m#1m3,m 3#,m !,"'"2-m .0m *'+'20m *m 0#!#.!'A,m "#m #2'*#,-m 7m #,m !-,1#!3#,!'Zm 3,m %#,m "',m ',2#0#1,2#m.0m1#0m,*'8"-m"#,20-m"#m3,m.- *!'A,m"#mZm#1.#!'*+#,2#m#,m +#*A,Zm 3,m #1.#!'#m +-"#*-m .0m #123"'0m #*m .0-!#1-m "#m +"30!'A,m .3#12-m /3#m 1#m #,!3#,20,m 40'#""#1m !*'+2<0'!1m 7m ,-m !*'+2<0'!1Ym -0m #(#+.*-Zm *1m 40'#""#1m "#*m 2'.-m (.&/*(-#-m .0#1#,2,m 3,m .'!-m #,m *m .0-"3!!'A,m "#m #2'*#,-m /3#m !-',!'"#m !-,m *m +"30#8m "#*m $032-m 7m !-,m 13m 1!'1'A,m ^&#**'#m 7m *4#'2Zm GOOI_Ym ',m #+ 0%-Zm *1m 40'#""#1m"#*m2'.-m()),/-m,-m.0#1#,2,m3,m.'!-m"#m#2'*#,-m7m,-m1#m.0-"3!#m 1!'1'A,m "#*m$032-Zm","-m$032-1m"#m*0%m4'"m^#,"**ZmGONN_Ym,m3+#,2-m"#m*m!-,!#,20!'A,m "#m#2'*#,-m#,m$032-m"#m+#*A,m",(.#-m.0-4-!m3,m"'1+',3!'A,m"#m*m"30#8m#,m*m.'#*m ^-1#m7m"$'#*"ZmGOON_Ym,m-20-m#123"'-m1#m&m"#+-120"-m/3#m3,m202+'#,2-m"#*m$032-m "#m +#*A,m !-,m Gj+#2'*!'!*-.0-.#,-m ^Gj_Zm 3,m ',&' '"-0m "#m *m !!'A,m "#m #2'*#,-Zm .0-4-!m 3,m 0#"3!!'A,m "#*m *,"+'#,2-m "#m *m .'#*m "#+-120,"-m *m '+.*'!!'A,m "#*m #2'*#,-m #,m *-1m !+ '-1m "#m *m .0#"m !#*3*0m "30,2#m #*m .0-!#1-m "#m +"30!'A,m #,m 40'#""#1m !*'+2<0'!1m ^'1&'7+m 7m !-*YZm HFFM_Ym *m +0'**#-m 7m #*m !-,2#,'"-m "#m !0-2#,-'"#1m#,m*m.'#*Zm*m$-0+!'A,m"#m*m8-,m"#m 1!'1'A,m.#"3,!3*0m7m*m0#1.'0!'A,m !*'+2<0'!m #,m #*m +#*A,m (.&)/*#m ",(.#-O 1-,m .0-!#1-1m "#.#,"'#,2#1m "#m #2'*#,-m ^*-0#1Zm HFFG\m 3@#8j*#,'31m 7m !-*YZm HFFLZm HFFN_Ym ',m #+ 0%-Zm -20-1m .0-!#1-1m /3#m -!300#,m"30,2#m*m+"30!'A,m!-+-m*m!3+3*!'A,m"#m8B!0#1Zm*m!'"#8Zm#*m.#1-m"#*m $032-Zm #*m 2+@-Zm #*m ,B+#0-m "#m 1#+'**1m 7m #*m !-,2#,'"-m "#m !0-2#,-'"#1m #,m *m !0,#m "#*m $032-m"#*m+#*A,m1#m&,m"#1!0'2-m!-+-m.0-!#1-1m',"#.#,"'#,2#1m"#m*m1>,2#1'1m"#m#2'*#,-m ^3@#8j*#,'31m7m!-*YZmHFFN_Ym -1m%#,#1mm1',21m7mm-6'"1m2+ '<,m&,m1'"-m"#1!0'2-1m!-+-m0#%3*"-0#1m#,m *m #6.0#1'A,m "#m #2'*#,-m #,m 40'1m #1.#!'#1m 7m 2#('"-1m ^0#+ ',1)'m 7m &#-*-%'1Zm GOOJ\m '-4,,-,'Zm HFFM_Ym + -1m 3+#,2,m 13m !2'4'""m !-',!'"'#,"-m !-,m #*m +-+#,2-m "#m +96'+m .0-"3!!'A,m "#m #2'*#,-m 7m +"30!'A,m "#*m $032-m ^*##!)#0m 7m #,"#Zm HFFF_Ym 3,m 1>Zm#*m.0-!#1-m#1m+3!&-m+91m!-+.*#(-m7m1#m1 #m/3#m#,m*m0#%3*!'A,m',2#04'#,#,m-20-1m %#,#1m #,20#m #**-1Zm $!2-0#1m "#m 20,1!0'.!'A,Zm Zm m 7m *m $+'*'m "#m 0#!#.2-0#1m "#m #2'*#,-m^830m7m!-*YZmHFFF_Ymm ',*+#,2#Zm""-m/3#m#,m,#)*-#-m*m$+'*'m"#m0#!#.2-0#1m^;FO;FO<FO>m7m <_m&m1'"-m '#,m'"#,2'$'!"m7m"#1!0'2m^2#.,-4m7m!)#0ZmHFFF_m7m1#m&m#4'"#,!'"-m KNm Genes candidatos para el TILLING (.,)/#9( *m .02'!'.!'A,m "#m #12-1m 0#!#.2-0#1m #,m *m +"30!'A,m "#m 40'1m $0321m !*'+2<0'!1Zm 1#m "#!'"'Am /3#m ;m #0m 3,m 3#,m !,"'"2-m .0m #*m Ym *m ',2#0<1m .-0m "#1!3 0'0m #*m +#!,'1+-m+-*#!3*0m0#1.-,1 *#m"#m*m0#%3*!'A,m"#m*m+"30!'A,m#1m#4'"#,2#m2,2-m m,'4#*m!-+#0!'*m!-+-m!'#,2>$'!-Ym-1m+32,2#1m#,m#*m%#,m;m.-"0>,m.-020m,3#4-1m !-,-!'+'#,2-1m1- 0#m*m0#!#.!'A,m"#*m#2'*#,-m7m#,m!-,1#!3#,!'Zm1- 0#m*m+"30!'A,m"#*m $032-Zm 3,/3#m !-+-m 7m 1#m &m +#,!'-,"-m ,2#0'-0+#,2#Zm 2-"-1m *-1m .0-!#1-1m "#m +"30!'A,m 7m #*m !0!2#0m !*'+2<0'!-m ,-m 1-,m #6!*31'4+#,2#m "#.#,"'#,2#1m "#m #12m &-0+-,m^'-4,,-,'mZmHFFG_Ymm m KOm (.,)/#9( Genes candidatos para el TILLINGO T LFm $.#0)- T T -1m- (#2'4-1m.0-.3#12-1m.0m#12m2#1'1m"-!2-0*m1-,m*-1m1'%3'#,2#1[m m jm#100-**0m*m.0'+#0m.*2$-0+m"#m+32,2#1mm.0m*m#1.#!'#m//'#-O'&)m m.02'0m"#m*m40'#""m"#m+#*A,m2'.-m'#*m"#m1.-mLHjGGIYmT T jm -,#0m m .3,2-m #*m +<2-"-m m 7m "#2#0+',0m *-1m .09+#20-1m /3#m -.2'+'8#,m *m "#2#!!'A,m "#m +32,2#1m 7m +','+'8#,m #*m ,B+#0-m "#m $*1-1m .-1'2'4-1Zm 32'*'8,"-m *m "#2#!!'A,m"#m+32,2#1m+#"',2#m"'%#12'A,m"#m&#2#0-"3.*#6m!-,m#,"-,3!*#11YT T jm 2#,#0m *1m 1#!3#,!'1m "#m *-1m %#,#1m 1#*#!!'-,"-1m Zm >FO I#-)J>m 7m ;m m .02'0m"#mLHjGGIYm#*'80m*m B1/3#"m"#m+32,2#1m.0m!"m%#,m#,m*m.- *!'A,m"#m m!-,m#*m- (#2'4-m"#m#,!-,200m+32,2#1m#,m!"m3,-m"#m#**-1m7m"#2#0+',0Zm1'm#1m .-1' *#Zm*-1m#$#!2-1m$#,-2>.'!-1m"#m#121m+32!'-,#1m1>m!-+-m!-+.0- 0m13m1#%0#%!'A,m #,m%#,#0!'-,#1m.-12#0'-0#1Ym m jm 12 *#!#0m 3,m !-+.0!'A,m #,20#m "-1m .- *!'-,#1m "#m Zm *m - 2#,'"m #,m #12#m 20 (-m "#m 2#1'1m "-!2-0*m 7m *m "#*m m !-,m #*m - (#2'4-m "#m !-+.0- 0m *-1m .09+#20-1m A.2'+-1m .0m *m - 2#,!'A,m "#m 3,m .- *!'A,m "#m m #$'!'#,2#m !-,m 3,m 21m "#m +32!'A,m!#.2 *#Ym m jm #*'80m 3,m #123"'-m "#m !-m #,m *-1m %#,#1m >m 7m ;O #,20#m LHjGGIm 7m GGIm !!#1'-,#1m"#m+#*A,Zm/3#m0#.0#1#,2,m*m40' '*'""m"#m*m#1.#!'#Zm.0-.-0!'-,"1m.-0m #*mET m jm,'!'0m*m!-,1203!!'A,m"#m3,m!29*-%-m"#m+32,2#1m$#,-2>.'!-1m#,m+#*A,Zm!2*-%,"-m *1m +32!'-,#1m #,!-,20"1m #,m JFFm $+'*'1m HZm !-,m *1m "#1!0'.!'-,#1m "#m *-1m $#,-2'.-1m +32,2#1m#,!-,20"-1YT T LG .,#&O3O'6.))- Creación y desarrollo de una población TILLINGO m m LH m Creación y desarrollo de una población TILLING .,#&O3O'6.))- m CMTTTT T TOTTTT T CMBMTTTTTTT m 0m *m #* -0!'A,m "#m *m .- *!'A,m "#m m #,m +#*A,m 1#m #1!-%'Am *m *>,#m "- *#m &.*-'"#m "#m *m 40'#""m "#m +#*A,m 2'.-m b'#*m "#m .-cm LHjGGIYm 12m *>,#m .0-4'#,#m "#m *m #+.0#1m '#&&-O #.9Fm *m !3*m .02'!'.Am #,m #*m .0-7#!2-m m ^HFFIjHFHIMm"#*m_m"A,"#m#129m#,+0!"-m#12#m20 (-Ym*m%#,2#m/3>+'!-mm ^2'*m #2,-m 3*$-,2-_m $3#m #*m +329%#,-m #1!-%'"-m .0m #* -00m #12m .- *!'A,m "#m m ""-m /3#m .0-4-!m +32!'-,#1m .3,23*#1Zm */3'*,"-m *1m %3,',1m 7m .0-4-!,"-m /3#m #,*!#,m !-,m *1m 2'+',1m 7m ,-m !-,m 13m 1#m !-+.*#+#,20'Zm !'2-1',m ^#%ZmGONJ_Ym T CMBMBTTTTTTTPAQT m+32!'A,m"#m*1m1#+'**1m1#m&'8-m#,m20#1m#6.#0'+#,2-1m"'12',2-1Zm7m/3#m#*m,B+#0-m"#m 1#+'**1m#0m+37m#*#4"-m^GMYFFFm1#+'**1m.0-6'+"+#,2#_m7m201m*m+32%<,#1'1Zm*1m 1#+'**1m "# >,m 0#.02'01#m #,m "-1m !#,20-1m !-* -0"-0#1m "-,"#m .-12#0'-0+#,2#m 1#m 0#*'80>m#*m!0#!'+'#,2-m"#m*1m.*,21Ym,m*m.0'+#0m2,"m^@-mHYFFK_m1#m+320-,mNYFFFm 1#+'**1m.0-6'+"+#,2#mm3,m!-,!#,20!'A,m"#mGPmm7m1#m+,"0-,mm*m#+.0#1m '#&&-O#.9O.0m13m!0#!'+'#,2-Ym,m*m1#%3,"m2,"m^@-mHYFFK_m1#m+320-,m-201mNYFFFm 1#+'**1m .0-6'+"+#,2#Zm .#0-m #12m 4#8m !-,m 20#1m !-,!#,20!'-,#1m "'12',21m "#m m ^FZKPZm GPm 7m GZKP_m 7m #,m #12m -!1'A,Zm 1#m +,"0-,m *m %03.-m !-* -0"-0m "#m *#,!'m ^jm ^,'4#01'""m -*'2<!,'!m "#m *#,!'__Ym ',*+#,2#Zm #,m #*m HYFFLm 1#m +320-,m .0-6'+"+#,2#m GYFFFm 1#+'**1m #,m 3,m 2#0!#0m 2,"Zm 7m /3#m +3!&1m "#m *1m .*,21m /3#m 1#m !0#!'#0-,m #,m *#,!'m "30,2#m #*m @-m HFFKm +30'#0-,m "# '"-m m 3,m ',!'"#,!'m#,m!+.-m"#*m!-*.1-m"#*m+#*A,Ym,m#12mB*2'+m2,"m1#m31Am3,mB,'!m"-1'1m "#m GYKm Pm "#m Ym *m .0-2-!-*-m "#m +32!'A,m "#m *1m 1#+'**1m 1#m -0%,'8Am #,m 20#1m ">1m !-,1#!32'4-1Ym *m .0'+#0m ">m 1#m &'"020-,m *1m 1#+'**1Ym 0m #**-m 1#m .31'#0-,m #,m 0#!'.'#,2#1m "#m .*912'!-m #,m 3,m .0-.-0!'A,m "#m HKm +*m "#m %3m !"m GFFm 1#+'**1Ym 1m 1#+'**1m 1#m "#(0-,m #,m %'2!'A,m 134#m "30,2#m GLm &-01Ym *m 1#%3,"-m ">m 1#m @"'Am #,m LI .,#&O3O'6.))- Creación y desarrollo de una población TILLINGO !+.,m#620!2-0m#*m%#,2#m+329%#,-mYm#m.*'!0-,m!-,!#,20!'-,#1m"#mFYKPZmGPm 7m GYKPm ^ *m HYG_m #,m *-2#1m "#m HFFm 1#+'**1m .-0m 0#!'.'#,2#m !-,m KFm +*m "#m %3Ym *m 202+'#,2-m1#m.*'!Am"30,2#mGNm&-01m#,m*m!+.,m#620!2-0m!-,m%'2!'A,m134#Ym m !+ TCMBOm2-1m!-00#1.-,"'#,2#1mm*1m"-1'1m"#mm32'*'8"1m.0m+320m*m.- *!'A,Zm*-1m$032-1m- 2#,'"-1m #,m*m%#,#0!'A,mGZm#*m,B+#0-m7m.-0!#,2(#m"#m*1m$+'*'1m!-,m1#+'**1m4' *#1m7m,-m4' *#1m#,m*m%#,#0!'A,m HYm',*+#,2#m#*m,B+#0-m"#m$+'*'1mHm',!*3'"1m#,m*1m.*!1m.--*m/3#m$-0+,m*m.- *!'A,m"#mYm m -1'1mm FZKPm m GPm m GYKPm m GPm m m +'*'1m!-,m 1#+'**1mHm,-m 4' *#1 +'*'1m!-,m 1#+'**1mHm!-,m .0'#,!'m4' *# +'*'1mHm#,m .--*1m"#mm HFJm GNm^NYNHP_ GNLm^OGYGNP_ GMMm HFOm HKm^GGYOLP_ GNJm^NNYFJP_ GKGm IOHm KKm^GJYFIP_ IIMm^NKYOMP_ HLOm HYIIKm IOOm^GMYFN_ GYOILm^NHYOHP_ GYMMGm IYGJFm JOMm HYLJIm HYILNm Em"#m $032-1mGm m *m2#0!#0m">m1#m0#!-%'#0-,m*1m1#+'**1m!-,m.0#!3!'A,m#,m3,m+**m"#m3,m.-0-m',$#0'-0m *m 2+@-m "#m *m 1#+'**m !#009,"-*m !-,m 3,m 0'"Ym #m .*'!0-,m 20#1m *4"-1Ym 0m #*m .0'+#0-m 1#m ',20-"3(-m *m +**m !-,m *1m 1#+'**1m "#,20-m "#m 3,m 41-m "#m .0#!'.'2"-1m "#m Km *'20-1m7m1#m"#(Am#,m%'2!'A,m"30,2#mJm&-01Ym0m#*m1#%3,"-m*4"-m1#m0#.'2'Am#*m+'1+-m .0-!#"'+'#,2-m .#0-m #,m #12m -!1'A,m "30,2#m Gm &-0Ym ',*+#,2#Zm #*m B*2'+-m *4"-m 1#m 0#*'8Am"#(,"-m*m+**m#,m3,m.'*m (-m%3m"#*m%0'$-m"30,2#mGm&-0Ym *m +2#0'*m "#m * -02-0'-m 31"-m .0m *-1m *4"-1m "#m *1m 1#+'**1m 1#m *#m @"'Am 3,m 1-*3!'A,m "#m Gm "#m m .0m ',!2'40m #*m Ym *m +'1+-m ">m 1#m .0#.00-,m *1m 1#+'**1m.0m*m%#0+',!'A,Ym#m0#.02'#0-,mKFm1#+'**1m#,m!"m ,"#(m"#m.*912'!-m!-,m 3,m 1#m "#m ..#*m "#m $'*20-m &B+#"-m 7m 1#m !3 0'#0-,m !-,m .*912'!-m 20,1.0#,2#m .0m +,2#,#0m *m &3+#""Ym #m <12#m +-"-m 1#m "#(0-,m 2-"m *m ,-!&#m #,m !9+0m .0m *m %#0+',!'A,m #,m !-,"'!'-,#1m A.2'+1m "#m *38m ^GHjHFm &-01m *38m !-,2',3_Zm 2#+.#0230m ^HNEjIFE_m7m%0"-m"#m&3+#""m"#!3"-1m^&'"02!'A,m.0#4'm"#m*1m1#+'**1m7m..#*m LJ Creación y desarrollo de una población TILLING .,#&O3O'6.))- &B+#"-m #,m *m 1#m "#*m 0#!'.'#,2#_Ym *m ">m 1'%3'#,2#Zm *1m 1#+'**1m %#0+',"1m $3#0-,m 201*""1mm131m0#1.#!2'4-1m"#12',-1m.0m1#0m.*,2"1Ym T CMBMCTTTTTBTTCT ,m 2-2*m "#m GMYFFFm 1#+'**1m 1#m 0#.02'#0-,m #,m *-1m "-1m "#12',-1m !-+-m 1#m &m "#1!0'2-m ,2#0'-0+#,2#Ym*m!0#!'+'#,2-m#,m 0#0m"#m0m#,m'#&&-O#.9m1#m&'8-m#,m',4#0,"#0-m 7m#,m!-,"'!'-,#1mA.2'+1m.0m#*m+#*A,m^DmHKjIFEm7mKKjLKPm"#m&3+#""_Ym ,m *#,!'m 1#m !0#!'Am *m .0'+#0m 2,"m "#*m HFFKm #,m !+.-Zm .#0-m 234'#0-,m 3,m %04#m ',$#!!'A,m.-0m!-*.1-m7m+30'#0-,m%0,m.02#m"#m*1m.*,21m1- 0#4'4'#,"-m3,m.#/3#@m .02#m "#m *1m NYFFFm 1#+'**1m .*,2"1m ','!'*+#,2#Ym -0m #12#m +-2'4-m .-12#0'-0+#,2#Zm 1#m .*,20-,m GYFFFm 1#+'**1m +91Zm 202"1m *m GZKPm "#m Zm #12m 4#8m #,m ',4#0,"#0-m .0m !-,20-*0m+91m*1m!-,"'!'-,#1m+ '#,2*#1m7m1- 0#2-"-m#4'20m',$#!!'-,#1Ymm T CMBMCMBTTTTTBTTT 12#m 20 (-m $3#m 0#*'8"-m .-0m #*m .#01-,*m "#m 1-.-02#m "#m !"m !#,20-m "-,"#m $3#0-,m "'120' 3'"1m *1m 1#+'**1m ^m 7m '#&&-O #.9_Ym m +#"'"m /3#m *1m .*,21m $3#0-,m !0#!'#,"-m1#m' ,m.-","-m"#m+,#0m/3#m1A*-m/3#"0m3,m0+m.0',!'.*m7m*%3,1m 1#!3,"0'1m "A,"#m 3,m 4#8m .0#!'"1m *1m $*-0#1m 1#m .-*','80-,m +,3*+#,2#Ym #m 32-$#!3,"0-,m3,m2-2*m"#mIYGJFm.*,21mGm^ *mHYG_Ym 0m *m .-*','8!'A,Zm .0'+#0-m 1#m #*'%'Am 3,m $*-0m $#+#,',m 7m 1#m *#m #620(#0-,m *-1m .<2*-1m !-,m!3'""-m"#(,"-m#*m%',#!#-m*' 0#m7m1- 0#2-"-m*m.02#m13.#0'-0m"#*m-40'-m^#12'%+_m !!#1' *#Ym-,m*m73"m"#m3,m!*4-m$'*"-m1#m0#!-%'Am3,m.-!-m"#m.-*#,m"#m*m,2#0m"#m 3,m$*-0m+1!3*',m"#m*m+'1+m.*,2Zm!-,m!3'""-m#m',2#,2,"-m/3#m<12#m.#0+,#!'#0m *-m+91m1#!-m.-1' *#Ym#m.*'!Am#12#m.-*#,m#,!'+m"#*m#12'%+m',2#,2,"-m2+ '<,m/3#m#*m -40'-m #1234'#0m *-m +91m 1#!-m .-1' *#m 7m /3#m !-,m *m &3+#""m #*m .-*#,m ,-m $#!3,"m #$'!'#,2#+#,2#Ym -12#0'-0+#,2#Zm 1#m !3 0'Am *m $*-0m !-,m 3,m 1- 0#m "#m ..#*m .0m #4'20m .-*','8!'-,#1m !038"1m7m1#m0-23*Am!-,m*m$#!&m.0m.-"#0m!-,20-*0m*-1m">1m"#m!3("-Ym+ '<,m1#m !-020-,m*1m0+1m*2#0*#1m/3#m#+#0%>,m"#m*m+'1+m0+m#,m*m!3*m1#m#,!-,20 m*m $*-0m.-*','8"Ym#m#12#m+-"-m*m.*,2m.-">m!-,!#,200m+91m0#!301-1m#,m#*m!3("-m"#*m $032-Ym #1.3<1m "#m 3,m 1#+,m .0-6'+"+#,2#m 1#m 0#2'0 m #*m 1- 0#m "#m ..#*m .0m !-,$'0+0m #*m !3("-Ym -0m *-m %#,#0*m 1#m - 234-m 3,m $032-m .-0m .*,2Ym -1m +#*-,#1m 1#m "#(0-,m!0#!#0m"30,2#mKKm">1m^_m.0-6'+"+#,2#Ym m m LK .,#&O3O'6.))- Creación y desarrollo de una población TILLINGO m CMBMCMCTTTTTCT ,m2-2*m"#mHYILNm$032-1mGm.0-"3(#0-,m1#+'**mHm4' *#m^ *mHYG_Ymm#12-1m$032-1m1#m *#1m #620(#0-,m 7m *'+.'0-,m *1m 1#+'**1Ym -12#0'-0+#,2#m 1#m %#0+',0-,m "'#8m 1#+'**1m "#m !"m$+'*'m7m"#m!"m.*9,23*m1#m#620(-m3,m"'1!-m"#m&-(Ym-1m"'#8m"'1!-1m"#m&-(m1#m +#8!*0-,m.0m#620#0m#*mm/3#m.-12#0'-0+#,2#Zm1#m-0%,'8Am#,m.*!1Ym*m0#12-m"#m 1#+'**1m"#m!"m$+'*'mHm1#mm%30"Am.0m$32301m.*'!!'-,#1m^'%30mHYG_Ym m m m (&30 TCMB[m1/3#+m"#*m.0-!#"'+'#,2-m32'*'8"-m.0m- 2#,#0m#*mm"#m*m.- *!'A,m"#mYm,m.0'+#0m *3%0m1#m+320-,m.0-6'+"+#,2#mGMYFFFm1#+'**1m*-m/3#m.#0+'2'Am*m32-$#!3,"!'A,m"#mIYGJFm.*,21mGm .0m*m- 2#,!'A,m"#mHYILNm$+'*'1mHYm#m!"m$+'*'mHm1#m%#0+',0-,m"'#8m',"'4'"3-1m7m1#m#620(-m#*mm "#m !"m 3,m "#m *1m "'#8m .*,21m .0m $-0+0m #*m .--*m "#m Ym 12#m m #1m *m 1#m "#m *m .*2$-0+m "#m Ymm m CMBMDTTTTT T CMBMDMBTTTTTTTT m#620!!'A,m"#*mm1#m&'8-m#,m#*mm!-,m#*m'2m!-+#0!'*m#17mOLm.*,2m','m '2m ^HKF_m ^_m "#m +-"-m /3#m 1#m .3"'#0-,m &!#0m 3,m %0,m ,B+#0-m "#m #620!!'-,#1m !-,m3,m*2-m0#,"'+'#,2-m7m#,m3,m.#0>-"-m"#m2'#+.-m0#"3!'"-Ym,m4#8m#620>"-m#*mZm 1#m +,"Am m ,3#120-m * -02-0'-m "#*m m #,m 0'*1m "-,"#m 1#m 4#0'$'!Am *m !*'""m 7m 1#m !3,2'$'!Am +#"',2#m %#*#1m "#m %0-1Ym #1.3<1m 1#m 20,1$'0'#0-,m *-1m 1m "#m 23 -1m m .*!1m"#mOLm^'%30mHYH_Zm- 2#,'#,"-m$',*+#,2#m3,m2-2*m"#mHKm.*!1m12-!)Ym m LL Creación y desarrollo de una población TILLING .,#&O3O'6.))- m m (&30 TCMC[m1/3#+m"#*m"'1#@-m1#%3'"-m.0m#* -00m*1m.*!1m.--*Ym%[mm%#,A+'!-Ym,'!'*+#,2#m1#m ',20-"3(#0-,m 2-"-1m *-1m 1m "#m !"m $+'*'m Hm #,m .*!1m .)%m !-,m 3,m !-,!#,20!'A,m +#"'m "#m KFm ,%ix*Ym "m .-!'**-m !-,2'#,#m #*m m "#m 3,m $+'*'m Hm !-+.3#12m .-0m GFm ',"'4'"3-1Ym -12#0'-0+#,2#m 1#m !-,12037#0-,m*1m.*!1m"#m"'*3!'A,Zm"'*37#,"-mmKm,%ix*m#*mm"#m!"m$+'*'Ym',*+#,2#m1#m-0%,'80-,m *1m.*!1m.--*m+#8!*,"-m*1m$+'*'1m"#m!320-m#,m!320-m#,m#*m-0"#,m/3#m+3#120m*m$'%30Ym m #m 0#*'80-,m !-.'1m "#m *1m .*!1m 12-!)m .#0-m #12m 4#8m !-,m #*m m "'*3'"-m GiGFYm #m @"'#0-,mHFmx*m"#*mm12-!)m!-,mGNFmx*m"#m%3m.0m- 2#,#0m3,m4-*3+#,m2-2*m"#m*m "'*3!'A,m"#m!"m$+'*'m"#mHFFmx*Ym0m*m!-,1203!!'A,m"#m*1m.*!1m.--*m1#m+#8!*0-,m #/3'+-*0+#,2#m *-1m 1m "#m !"m !320-m $+'*'1Ym *m "'1#@-m 1#m +3#120m #,m *m '%30m HYHY T CMBMDMCTTTTTT *m.0-2-!-*-m31"-m#129m 1"-m#,m#*m.0-2-!-*-m.3 *'!"-m.-0m-7*#m,"m-7*#m^GYOOF_m *'%#0+#,2#m+-"'$'!"-Ym*m+2#0'*m"#m.02'"m$3#m3,m.#/3#@-m"'1!-m"#m&-(m#,m#12"'-m "#m.*9,23*Ym*m"'1!-m"#m&-(m1#m',20-"3(-m#,m3,m**(), m"#mGZOm+*m#*m!3*m1#m13+#0%'Am #,m,'20A%#,-m*>/3'"-m*-m+91m09.'"+#,2#m.-1' *#Ym-12#0'-0+#,2#m1#m0#2'0Am#*m**(), m7m LM .,#&O3O'6.))- Creación y desarrollo de una población TILLINGO 1#m 20'230Am #*m +2#0'*m !-,m *m 73"m "#m 3,m .#/3#@m 0-!m .0m "#4-*4#0m *m +3#120m 20'230"m *m ,'20A%#,-Ym -12#0'-0+#,2#Zm 1#m *#m @"'Am KFFm x*m "#m 2+.A,m "#m #620!!'A,m -7*#m ^,#6-m Y$_m .0#!*#,2"-m m LKEm +#8!*9,"-m 134#+#,2#m .0m "#1.3<1m ',20-"3!'0*-m*m @-m+0>mmLKEm"30,2#mIFm+',32-1Ym #m @"'#0-,m KFFm x*m "#m !*-0-$-0+-m '1-+>*'!-m #,m .0-.-0!'A,m HJ[G\m 1#m +#8!*Am 7m 1#m !#,20'$3%Am m GGYFFFm 0.+m m Dm + '#,2#m "30,2#m GFm +',32-1Ym #m #1m !#,20'$3%!'A,m 1#m 0#!3.#0Am *m $1#m !3-1m 7m 1#m *#m @"'#0-,m IKFm x*m "#m Hj.0-.,-*m ^'1-.0-.,-*_m $0>-m !#,20'$3%,"-*-m Km +',32-1m m GFYFFFm 0.+m .0m .-"#0m .0#!'.'20m *-1m 9!'"-1m ,3!*#'!-1Ym *m m .0#!'.'2"-m 1#m *#m @"'#0-,m HFFm x*m "#m 2+.A,m "#m *4"-m "#m -7*#m ^,#6-m Y%_m "#(9,"-*-m0#.-10m3,m+>,'+-m"#mHFm+',32-1mmjHFEZm"#1.3<1m1#m!#,20'$3%AmIm+',32-1mm GFYFFFm 0.+m 7m m Dm + '#,2#Ym ',*+#,2#m 1#m #620(-m #*m 1- 0#,",2#m .0m "#(0m #*m .#**#2m 1#!9,"-1#m"30,2#mIFm+',32-1Ym,m4#8m1#!-m1#m0#131.#,"'Am#*m.#**#2m!-,mKFmx*m"#m%3m Zm 7m 1#m "#(0-,m *1m +3#1201m m JEm 2-"m *m ,-!&#m .0m $!'*'20m 3,m 3#,m 0#131.#,1'A,m"#*mYm CMBMDMDTTTTTT 0m *m !-+.0- !'A,m "#m *m !*'""m 7m !,2'""m "#*m m "#m *1m #620!!'-,#1Zm 1#m 1#.00-,m *-1m $0%+#,2-1m #,m %#*#1m "#m %0-1Ym -1m %#*#1m !-,2#,>,m 3,m GPm "#m %0-1m ^m "#m 0-,"'1_m #,m m FYHK6m ^,#6-m Y'_m 7m Gm x*iGFFm +*m "#m 0-+30-m "#m #2'"'-Ym m #*#!20-$-0#1'1m"#m0#*'8Am!-,m2+.A,mZm7m1#m!0%0-,m*1m+3#1201m#,m%3m(3,2-m!-,m #*m !-*-0,2#m "#m !0%m ^GiK_m m ^,#6-m Y&_Ym 3,2-m !-,m *1m +3#1201m 1#m !0%Am 2+ '<,m #*m +0!"-0m "#m .#1-m +-*#!3*0m "#.#,"'#,"-m "#*m2+@-m "#*m $0%+#,2-m m "#2#!20m ^m "#*m$%-mwm-m*m+'6_Ym',*+#,2#Zm1#m.*'!Am3,m4-*2(#m"#m#,20#mNKjGFFmYmm LN .,#&O3O'6.))- Detección e identificación de los mutantes CMCTTTTTTT m ,m4#8m#*#%'"-m#*m%#,m"',m7m- 2#,'"m13m1#!3#,!'m#1.#!>$'!m"#m*m40'#""mLHjGGIZm !-,m*m/3#m&#+-1m"#100-**"-m*m.- *!'A,m"#mZm1#m.0-!#"'Amm*m"#2#!!'A,m"#m *-1m+32,2#1Ym*m.0-2-!-*-m#129m 1"-m#,m!320-m$1#1[mG_m+.*'$'!!'A,m"#*m$0%+#,2-m "#*m %#,m +#"',2#m Zm H_m #1,230*'8!'A,m 7m 0#,230*'8!'A,m "#m *-1m +.*'!-,#1Zm I_m '%#12'A,m"#m*-1m&#2#0-"B.*#6ZmJ_m'13*'8!'A,m"#m*-1m$0%+#,2-1m"#m"'%#12'A,m#,m%#*#1m "#m!0'*+'"m4#02'!*#1m^'%30mHYI_Ym m m m (&30 T CMD[m 1/3#+m "#*m .0-2-!-*-m "#m Ym _m -.O Zm 1#%3,"m +.*'$'!!'A,m ^+91m #1.#!>$'!_m "#*m $0%+#,2-m m ,*'80m !-,m !# "-0#1m +0!"-1m !-,m $*3-0#1!#,!'Ym _m #1,230*'8!'A,m "#m *-1m $0%+#,2-1m 7m 0#,230*'8!'A,m .0-4-!,"-m *-1m &#2#0-"B.*#6m #,20#m *-1m $0%+#,2-1m ,-m !-+.*#+#,20'-1m .-0m !-,2#,#0m 3,m LO .,#&O3O'6.))- Detección e identificación de los mutantesO +32!'A,Ym!_m'%#12'A,m!-,m*m#,"-,3!*#1m#1.#!>$'!m"#m&#2#0-"B.*#6m7m.-0m*-m2,2-m"#m*-1m$0%+#,2-1m/3#m !-,2'#,#,m +32!'A,Ym -1m *#*-1m 1'*4#120#1m ,-m $-0+09,m &#2#0-"B.*#6m 7m .-0m *-m 2,2-Zm ,-m 1-,m "'%#0'"-1Ym "_m #1,230*'8!'A,m 7m 4'13*'8!'A,m "#m *-1m $0%+#,2-1m #,m %#*#1m "#m !0'*+'"Ym ,m #*m jm JIFFm .-"#+-1m 4'13*'80m*-1m"-1m!,*#1m^mMFFm7mNFF_m.-0m1#.0"-m7m!-,$'0+0m*1m+32!'-,#1m+#"',2#m#*m!9*!3*-m"#*m 2+@-m "#*m $0%+#,2-m "'%#0'"-Ym -,m *m 13+m "#m *-1m $0%+#,2-1m "'%#0'"-1m 7m 4'13*'8"-1m #,m + -1m !,*#1m "# #m- 2#,#01#m#*m$0%+#,2-m,-m"'%#0'"-m-0'%',*Ymm m CMCMBTTTTTTT 0m .*'!0m #*m +<2-"-m "#m m .0'+#0-m &!#m $*2m "#$','0m #*m %#,m "',m /3#m /3#0#+-1m #123"'0m 7m "#*m !3*m /3#0#+-1m #,!-,200m +32,2#1Ym ,m 4#8m #*#%'"-m #*m %#,m &!#m$*2m1#!3#,!'0*-m#,m*m#1.#!'#m-m40'#""m!-,m*m/3#m1#m&7m- 2#,'"-m*m.- *!'A,m "#mm.0m3,m#$'!'#,2#m"'1#@-m"#m*-1m!# "-0#1Ym 0m*m+.*'$'!!'A,m"#m*-1m%#,#1mZmI#-)J>m7O;m1#m 31!0-,m1m#,m*m 1#m"#m "2-1m "#m m ^!23*+#,2#m 1#m .3#"#m #,!-,200m #12m ',$-0+!'A,m #,m 555Y'!3%'Y-0%_m +'#,201m /3#m .0m #*m %#,m >m *-1m !# "-0#1m 7m #12 ,m "'1#@"-1m ,2#0'-0+#,2#m ^'#2-m 7m !-*YZm HFFLJYm 0m !"m 3,-m "#m #**-1m 1#m #,!-,20Am 3,m 3,'%#,m ^555Y'!3%'Y-0%_m7mm.02'0m"#m#1#m$0%+#,2-m1#m"'1#@0-,m*-1m!# "-0#1m.0m#+.#80mm 1#!3#,!'0m#*m%#,m#,2#0-m-m0#%'-,#1m!-,!0#21m"#*m+'1+-Ym0m#*m"'1#@-m"#m!# "-0#1m1#m 31Am #*m .0-%0+m .0'+#0Im ^&22.[ii$0-"-Y5'Y+'2Y#"3_m 7m #,m "#2#0+',"1m -!1'-,#1m 1#m "'1#@0-,m*-1m!# "-0#1m+,3*+#,2#Ym !23*+#,2#Zm 7m %0!'1m m *m "'1.-,' '*'""m "#m *m 1#!3#,!'m "#*m %#,-+m "#*m +#*A,Zm ,-m 1#0>m ,#!#10'-m 1#!3#,!'0m *-1m 1m .3#12-m /3#m 7m "'1.-,"0>+-1m "#m *m 1#!3#,!'m #1.#!'$'!m"#m!"m%#,m#,m*m#1.#!'#m"#m#123"'-Ym T CMCMBMBTTTTTPQT ,m 4#8m "'1#@"-1m *-1m !# "-0#1Zm 1#m -.2'+'80Am *m +.*'$'!!'A,m +#"',2#m m #,m %0"'#,2#m "#m 2#+.#0230m .0m "#2#0+',0m *m 2#+.#0230m "#m &' 0'"!'A,m A.2'+Ym 12m m!-,1'12#m#,m.0#.00m*m+'1+m+#8!*m^"#mm7m!# "-0#1_m7m.0- 0*mm"'12',21m 2#+.#02301m"#m&' 0'"!'A,m.0m.-"#0m- 1#040m#,m!3*m#1m+91m#1.#!>$'!Ym 0m.0#.00m*mm#129,"0m1#m32'*'80-,m"#mGFjKFm,%m"#mZm2+.A,m mGFm^ m G[m %*Hm GYKm +Zm *m KFm +Zm 0'1j*m GFm +m .m NYIZm %#*2',m FYFFGP_Zm FYJm +m "#m !"m,3!*#A2'"-ZmFYJmxm"#m!"m!# "-0Zm7m#,m$3,!'A,m"#m!"m.0#(m"#m!# "-0#1Zmm"#m GYKm+mmIYKm+m"#m%*Hm7mHm"#m/m.-*'+#01Ym*m4-*3+#,m$',*m#129,"0m32'*'8"-m #0m"#mHKmx*Ymm0#!!'A,m1#m0#*'8 m#,m2#0+-!'!*"-0#1m#,#m+.mm712#+mOMFFZm MF Detección e identificación de los mutantes .,#&O3O'6.))- HMHFm &#0+*m 7!*#0m ^..*'#"m '-1712#+1_m 7m jHFFm #*2'#0m &#0+*m 7!*#0m ^ m #1#0!&_m.0mm*1m0#!!'-,#1m"#mm#,m%0"'#,2#1m"#m2#+.#0230Ym *m .0-%0+m #12,"0'8"-m !-,1'12>m "#m 3,m .0'+#0m !'!*-m "#m "#1,230*'8!'A,m "#m Hm +',32-1m m OJEZm 7m IKm !'!*-1m "#m "#1,230*'8!'A,m "#m *m !"#,m ^HFm 1#%3,"-1m m OJE_Zm &' 0'"!'A,m"#m*-1m!# "-0#1m^2#+.#0230m#1.#!>$'!m.0m!"m.0#(_Zm7m#*-,%!'A,m"#*m $0%+#,2-m ^"#m IFm 1#%3,"-1m m Gm +',32-m #,m $3,!'A,m "#*m 2+@-m "#*m +.*'!A,m m MHm E_Ym ',*+#,2#m 1#m @"'Am 3,m !'!*-m "#m Km +',32-1m m MHEm .0m ! 0m *m #*-,%!'A,m 7m 1#m +,234-m*m0#!!'A,mmGHEYm m CMCMBMCTTTT -1m $0%+#,2-1m 0#13*2,2#1m $3#0-,m .0'+#0+#,2#m .30'$'!"-1m !-,m #*m #!"O /,O ,)/.O /,# #.#)(O #.m ^-!&#_m .0m .-12#0'-0+#,2#m 1#0m 1#!3#,!'"-1Ym ,m !"m 0#!!'A,m "#m 1#!3#,!'!'A,m 1#m @"'#0-,m Im x*m ^GFjHKm ,%_m "#*m $0%+#,2-m "#m m .30'$'!"-m /3#m "#1# m1#!3#,!'01#ZmHmx*m"#m2+.A,mm^HFFm+m0'1j*ZmOYF\mKm+m%*H_ZmHmx*m "#m '%m 7#m ^#!3L,'#(.),O 0;E;O 3&O +/(#(!O #._m 7m $',*+#,2#m Im x*m "#m %3m m .0m !-+.*#20m #*m 4-*3+#,m 2-2*m "#m GFm x*Ym 0m 1#!3#,!'0m #*m $0%+#,2-m 1#m &'8-m 3,mm"#m1#!3#,!'!'A,m/3#m!-,12 m"#mHKm!'!*-1Zm"#m20#1m.1-1\m3,m.0'+#0m.1-m.0m *m "#1,230*'8!'A,m m OLEm "30,2#m GFm 1#%3,"-1Zm 3,m .1-m "#m &' 0'"!'A,m "#m *-1m !# "-0#1m m KFEm "30,2#m Km 1#%3,"-1m 7m 3,m 2#0!#0m .1-m "#m #*-,%!'A,m m LFEm "30,2#m Jm +',32-1Ym -12#0'-0+#,2#m1#m.0-!#"'Amm*m.0#!'.'2!'A,m"#*mm#,m.*!YmmGFmx*m"#*m4-*3+#,m"#m *m0#!!'A,m"#m1#!3#,!'!'A,m1#m*#m@">,mGFmx*m"#m%3m7m.-12#0'-0+#,2#ZmHmx*m"#mm GHKm+ZmHmx*m"#m!mIm.mJZLZm7mKFmx*m"#m2m 1-*32-Ym#1.3<1m"#m+#8!*0*-m1#m "#( m.0#!'.'20m#*mm"30,2#mGKm+',32-1m7m1#m!#,20'$3% mmIYFFFm0.+m"30,2#mIFm +',32-1Zm 1#m ',4#02>m *m .*!m 7m 1#m #*'+', m #*m 1- 0#,",2#Ym 3#%-m 1#m 0#*'8 m 3,m !#,20'$3%!'A,m!-02mmGYFFFm0.+m.0m"#1.3<1m@"'0*#mGKFmx*m"#m2m*mMFmPYm,m4#8m +#8!*"m *m .*!m .-0m ',4#01'A,m 1#m !#,20'$3% m m IYFFFm 0.+m "30,2#m GFm +',32-1m #*'+',,"-m .-0m 1-0!'A,m #*m 1- 0#,",2#Ym ',*+#,2#m 1#m .-">m &!#0m 3,m !#,20'$3%!'A,m!-02m!-,m*m.*!m',4#02'"m#,!'+m"#m..#*m 1-0 #,2#m.0m1#%300m3,m 1#!"-m +91m ',2#,1-m "#*m .0#!'.'2"-Ym ,m 4#8m .0#!'.'2"1m *1m 1#!3#,!'1m 1#m 0#131.#,"'#0-,m !"m 3,m "#m #**1m !-,m GHm x*m "#m $-0++'"m ''m 7m 1#m !0%0-,m #,m #*m 1#!3#,!'"-0mIGIF*Ym m m MG .,#&O3O'6.))- Detección e identificación de los mutantesO CMCMBMDTTTTT 1m 1#!3#,!'1m $3#0-,m ,*'8"1m & '23*+#,2#m !-,m #*m .0-%0+m +/(",O >EAEO #m !"m %#,m 1#m 32'*'8Am #*m -02A*-%-m "#m *m #1.#!'#m +91m !#0!,m /3#m &3 '#0m "'1.-,' *#m #,m *m 1#m"#m"2-1m!-+-m+-"#*-Ym#m#12#m+-"-m.3"'+-1m- 2#,#0m*m1#!3#,!'m#6!2m"#m!"m %#,m -m "#*m $0%+#,2-m "#m ',2#0<1m #,m *m 40'#""m LHjGGIm 7m *-!*'80m *m .-1'!'A,m "#m ',20-,#1m7m#6-,#1Ym T CMCMCTTTTTTTTT ,m 4#8m - 2#,'"m *m 1#!3#,!'m #1.#!>$'!m "#m *-1m %#,#1m #,m *m 40'#""m LHjGGIZm .0-!#"'+-1m *m "'1#@-m "#m !# "-0#1m /3#m +.*'$'!0>,m *m 0#%'A,m "#m ',2#0<1m .0m .-12#0'-0+#,2#m 1#0m ,*'8"m +#"',2#m #*m +<2-"-m Ym 0m *m "#2#!!'A,m "#m *-1m +32,2#1m1#m0#/3'#0#m3,m+.*'$'!!'A,m+37m#1.#!>$'!Zm#1m.-0m#**-m/3#m1#m"'1#@0-,m"-1m .0#(1m "#m !# "-0#1m .0m !"m 0#%'A,Ym ,m +.*'$'! m 3,m $0%+#,2-m +7-0m "#m *m 0#%'A,m "#m ',2#0<1m +'#,201m /3#m *m -20m .0#(m "#m !# "-0#1m #12 m "'1#@"m m 3,m "'12,!'m "#m #,20#m GFm 7m HFm . m +91m "#*,2#m "#m *m .0#(m ,2#0'-0Zm &!'#,"-m 1>m 3,m +.*'$'!!'A,m "#m 3,m $0%+#,2-m .0#4'+#,2#m 7m +.*'$'!"-m -m "- *#m +.*'$'!!'A,m ^-.O_Ym 0m *m #*#!!'A,m "#*m $0%+#,2-m m +.*'$'!0m 1#m 32'*'8Am #*m .0-%0+m m ^))(-O *.#'#4O .)O #-)0,O &.,#)/-O -#)(-m ^&22.[ii555Y.0-5# Y-0%i',.32i__Ym m .#0+'2#m'"#,2'$'!0m*1m8-,1m"#*m%#,m/3#m3,m4#8m+32"1m2'#,#,m+91m.0- '*'""m"#m 40'0m #*m +',-9!'"-m #,m 8-,1m !-,1#04"1m "#m *m .0-2#>,m 7m .-0m *-m 2,2-Zm +91m .0- '*'""m"#m$#!20mm*m$3,!'-,*'""m"#m*m+'1+Ym*m.0-%0+m.#0+'2#m',20-"3!'0m 40' *#1m!-+-m*m#1.#!'#m/3#m1#m+32Zm7m#*m+<2-"-m7i-m%#,2#m/3>+'!-m!-,m#*m/3#m1#m&m 0#*'8"-m*m+32!'A,m.0m.-"#0m0#*'80m#*m!9*!3*-Ym,m4#8m'"#,2'$'!"m#12m0#%'A,m1#m "'1#@0-,m *-1m !# "-0#1m #1.#!>$'!-1m !-,m Zm .0'+#0Im -m +#"',2#m "'1#@-m +,3*m ^,#6-mY_Ym m CMCMDTTTTTT 0!'1m*m"'1#@-m"#m"-1m.0#(1m"#m!# "-0#1m7mm*m-.Om1#m- 2#,>m3,m.0-"3!2-m +3!&-m +91m #1.#!>$'!-Ym 0m *m .0'+#0m m ^.02"-m HYHYGYG_m 1#m 32'*'80-,m *-1m !# "-0#1m1',m+0!(#Ymm0#!!'A,m"#mm1#m0#*'8Amm.02'0m"#m*m+#8!*m#12,"0'8"m +-120"m#,m*m *mHYHYm m MH .,#&O3O'6.))- Detección e identificación de los mutantes !+ TCMC[m-+.-1'!'A,m"#m*m0#!!'A,m"#mm#,m#*m.0-2-!-*-m"#mm^g,#6-mY Yggm.0-!#"#,2#m"#m !"m.-!'**-m"#m*1m.*!1m.--*_m m .-"$-20 "(>-T (-("( +T .-"$-20 "(>-T %(- +T R0$ ""(>-T GFm+m Gm+m HYKmx*m HKm+m Km+m GFm+m GFm+m HZKm+m FZHm+m FZJm+m FZJm+m HYKmx*m Gmx*m Gmx*m Gmx*m Km3ix*m Km3m Gmx*m ggm Km,%ix*m ^.0-6_m GFm,%m Hmx*m -*3+#,m 2-2*m m m HKmx*m .,/.-$-2$T +.A,m"#m gm %*Hm "1m # "-0mm # "-0mm /m -*'+#01m m CMCMDMBT$ T 0m*m1#%3,"mm^-.O_m^'%30mHYIY_m1#m32'*'8Am#*m.0-2-!-*-m,2#0'-0m3,/3#m #,m #12#m !1-m 1#m @">,m *-1m !# "-0#1m +0!"-1m .0m jZm "#m +-"-m /3#m *-1m !# "-0#1m "'0#!2-1m #129,m +0!"-1m !-,m #*m $*3-0-!0-+-m MFFm ^0-(-_m 7m *-1m !# "-0#1m 0#4#01-1m !-,m #*m $*3-0-!0-+-m NFFm ^4#0"#_Ym *m m @"'"-m #0m #*m .0-"3!2-m "#m *m .0'+#0m Ym *m .0-%0+m "#m m 32'*'8"-m #0m #*m +'1+-m /3#m #,m *m .0'+#0m +.*'$'!!'A,m 3,/3#m !+ ',"-m *m 2#+.#0230m "#m &' 0'"!'A,m .0m !"m .0#(m "#m !# "-0#1Ym ,m #121m +.*'$'!!'-,#1m "# >m 2#,#01#m .0#!3!'A,m 7m 1#m "# >,m #,4-*4#0m *-1m 23 -1m !-,m ..#*m "#m *3+','-m #,m 2-"-m +-+#,2-m 7m /3#m *-1m $*3-0-!0-+-1m m 1#m "#%0",m*m#6.-,#01#mm*m*38Ym ',*+#,2#Zm*m4'13*'8!'A,m"#*m.0-"3!2-m"#mm1#m0#*'8Am#,m%#*#1m"#m%0-1m*mGPm7m 2',!'A,m !-,m 0-+30-m "#m #2'"'-Ym #m 31Am +0!"-0m "#m .#1-m +-*#!3*0m "#!3"-m m !"m $0%+#,2-m ^*O #2m .0m $0%+#,2-1m "#m GFFjGFFFm . m 7m wm "'%#0'"-m !-,m #(Cm .0m $0%+#,2-1m "#m +91m "#m GFFFm . _m .0m !-+.0- 0m /3#m #*m +.*'!A,m - 2#,'"-m #0m #*m !-00#!2-Ym CMCMETTTT 12#m.1-m#1m,#!#10'-m.0m*m"#2#!!'A,m"#m*m+32!'A,m^'%30mHYIY _Ym"m.-!'**-m"#m *1m .*!1m .--*m !-,12m "#m m "#m Jm $+'*'1m Hm "'12',21m ^!"m 3,m "#m #**1m !-,m GFm ',"'4'"3-1Zm.-0m*-m2,2-m#,m!"m.-!'**-m&7mJFm',"'4'"3-1m0#.0#1#,2"-1_Ym*mm#129m +32"-m *m 80m 7m #,m !"m .-!'**-m .3#"#m & #0m .0#1#,!'m "#m *#*-1m 1'*4#120#1m 7m *#*-1m MI .,#&O3O'6.))- Detección e identificación de los mutantesO +32"-1Ym m $-0+!'A,m "#*m &#2#0-"B.*#6m 1A*-m 1#m "09m #,20#m $0%+#,2-1m !-,m *%B,m !+ '-m"#m 1#m-mZm#1m"#!'0Zm#,20#m*#*-1m"'12',2-1m^+32"-m7m,-m+32"-_Ym 0m*m$-0+!'A,m"#*m&#2#0-"B.*#6m1#m1-+#2'#0-,m*1m1m!-,m+0!(#m^-.O_mm 3,m!'!*-m"#m"#1,230*'8!'A,m7m*3#%-m3,m0#,230*'8!'A,m*#,2Ym0m#**-m1#m',20-"3(-m *m -.O O #,m #*m 2#0+-!'!*"-0m HFFm !-,m 3,m .0-%0+m "#m OJEm "30,2#m GFm +',32-1m7m*3#%-m3,m%0"'#,2#m"#mOJEmmNEm"'1+',37#,"-mjFYGEi1m7m$',*'8,"-mmJEYm m CMCMFTTTT T CMCMFMBTTTTTTTTT 0m #*#%'0m !-00#!2+#,2#m *m "'*3!'A,m "#m *m #,8'+m ()O 1#m 31Am *m ',$-0+!'A,m .0-.-0!'-,"m .-0m #*m * -02-0'-m "#*m Zm /3#m $3#m #*m !#,20-m /3#m ,-1m .0-.-0!'-,Am *m #,8'+m !-,!#,20"Ym ,m #*m ,#6-m Y!m .3#"#m 4#01#m #*m %09$'!-m #* -0"-m .-0m #12#m * -02-0'-m"A,"#m1#m.3#"#m"#2#0+',0m*m"'*3!'A,m"#m#,8'+m,#!#10'm#,m$3,!'A,m"#m*m !-,!#,20!'A,m"#mm- 2#,'"-m#,m#*m.0-"3!2-m"#m*mYm m !-,!#,20!'A,m +#"'m "#m m - 2#,'"m #,m ,3#120-m * -02-0'-m #,m *1m !-,"'!'-,#1m !'2"1m,2#0'-0+#,2#m#0m"#*m0,%-m"#mJFjKFm,%Zm.-0m#12#m+-2'4-m7m& '#,"-m0#*'8"-m .03# 1m 2#12m .0m !-00- -00m *m ',$-0+!'A,m "#*m %09$'!-m 1#m 32'*'8Am *m "'*3!'A,m GiKFFFm ^,#6-mY!_m"#m*m#,8'+m()Em m CMCMFMCTTTTTTTTT 0m!"m0#!!'A,m"#m"'%#12'A,m^'%30mHYIY!_m^7m2#,'#,"-m#,m!3#,2m/3#m*m!,2'""m"#m .0-"3!2-m"#mm1'#+.0#m-1!'* m#,20#mJFm7mKFm,%_m1#m@"'AmIx*m"#*m.0-"3!2-m"#mZm Im x*m "#m 2+.A,m .0m *m "'%#12'A,m ^,#6-m Y#_Zm Im x*m "#m ()m ^GiKYFFF_m 7m HGm x*m "#m %3m m.0m**#%0mm*-1mIFmx*m"#m4-*3+#,m2-2*Ym12m0#!!'A,m1#m',!3 mmJKEm"30,2#m HFm+',32-1Ym-12#0'-0+#,2#Zm.0m"#2#,#0m*m0#!!'A,m"#m"'%#12'A,Zm1#m@"'#0-,mKmx*m"#m mFYGKmm+,2#,'#,"-m*m0#!!'A,m#,m&'#*-m7m.0-2#%'"m"#m*m*38Ym T CMCMFMDTTTTTTT 0m*m.30'$'!!'A,m.0'+#0-m"# >m.0#.001#m*m.*!m"#m.30'$'!!'A,m**#,,"-m*m.*!m "#m!0%m!-,m*"2m#,m.-*4-m^#.&"#6mjKFm3.#0$',#Zm+#01&+m'-1!'#,!#1_Zm7m #6.,"'0m !-,m *m #1.923*m /3#m **#4m "(3,2m *m .*!m "#m !0%m #.&"#6m KFm ^FOLJKZm '**'.-0#_Ym ,m 4#8m '#,m **#,-1m *-1m .-!'**-1m 7m *m .*!m *'+.'m 1#m ',4'02'Am 1- 0#m 3,m .*!m $'*20-m '**'.-0#m ^3*2'!0##,j_m "#(,"-m /3#m #*m *"2m !7#0m #,m !"m.-!'**-Ym@"'+-1mIHKmx*m"#m%3mmm!"m.-!'**-m"#m*m.*!m$'*20-m.0m/3#m#*m MJ Detección e identificación de los mutantes .,#&O3O'6.))- *"2O .-*'+#0'80m 7m $-0+0m *m 0#1',m /3#m .30'$'!0>m #*m .0-"3!2-m "#m *m "'%#12'A,Ym ,m4#8m@"'"m#*m%3m&'8-m$*2m#1.#00m3,m+>,'+-m"#m3,m&-0m.0m/3#m*m0#1',m 1-0 '#0m13$'!'#,2#+#,2#m#*m%3Ym #1.3<1m "#m 3,m &-0m 1#m !#,20'$3%Am *m .*!m $'*20-m !-,m 3,m .*!m "# (-m ^'!0-.*2#m 0#',#0m "#m OLm .-!'**-1_m m HYFFFm 0.+m "30,2#m Hm +',32-1m .0m 1#!0m *m 0#1',Ym ,m 4#8m #6.3*1"m #*m %3m *m .*!m #12 m *'12m .0m !0%0m *-1m IKm x*m "#m *m "'%#12'A,m "#m &#2#0-"B.*#6Ym 0m '1*0m *m +3#120m 1#m !-*-!Am *m .*!m "#m 0#!-*#!!'A,m ^*!m _Zm & '#,"-m!0%"-m.0#4'+#,2#mKmx*m"#m83*m!-,m$-0++'"m#,m!"m.-!'**-Zm"# (-m"#m*m .*!m $'*20-m ^.0#12,"-m 2#,!'A,m m /3#m *m -0'#,2!'A,m "#m *1m "-1m .*!1m 1#m *m +'1+_Ym -12#0'-0+#,2#m1#m@"'#0-,m*-1mIKmx*m"#m*m"'%#12'A,m#,m!"m.-!'**-m7m1#m!#,20'$3%Am-20m 4#8mHm+',32-1mmHYFFFm0.+Zm#*37#,"-m1>m*m+3#120Ym0m#*m1#!"-m7m!-,!#,20"-m"#m*m +3#120m1#m"#.-1'2Am*m.*!m#,m#*m*OO^ -3,mmGFFO_mmLKEm"30,2#mJKm+',32-1Ym #m #12#m +-"-m 1#m 0#"3(-m #*m 4-*3+#,m "#m %3m 7m 1#m - 234-m *m +3#120m !-,!#,20"m 7m m .3,2-m.0m*m!0%m#,m#*m%#*m"#m!0'*+'"m4#02'!*Ym m CMCMGT T T T T T T T T TTT m CMCMGMBTTTTTT 0m*m1#.0!'A,m"#m*1m+3#1201m&#+-1m32'*'8"-m#*m1#!3#,!'"-0mjmJIFFYm0m *m .0#.0!'A,m "#*m %#*Zm .0'+#0-m 1#m +-,20-,m "#!3"+#,2#m *-1m !0'12*#1m "#*m jm ^!0'12*#1m202"-1m#1.#!>$'!+#,2#m.0m*m!-00#!2m!.2!'A,m7m#*m,9*'1'1m"#*m*91#0m"#m*m +'1+m+9/3',_Ym,20#m*-1m"-1m!0'12*#1m1#m!-*-!0-,m*-1m#1.!'"-0#1m"#mHKm++m"#mj Zm7m1#m#,!(0-,m*-1m!0'12*#1m!-,m*1m.'#81m.0m#12#m+-,2(#Ym,m4#8m+-,2"-1m1#m .0#.0Am *m +#8!*m !-,m HKm +*m "#m !0'*+'"m ^/&O;BG;MO+/(#(!O,HO.#)(&O #!()-.#-_Zm HFm x*m "#m m 7m GFFm x*m "#m m ^.#013*$2-m "#m +-,'-_Ym m +#8!*m 1#m %'2Am*'%#0+#,2#m7m1#m 1-0 'Am#,m3,m(#0',%m"#mKFm+*m.0m',7#!20*m',+#"'2+#,2#m #,m #*m +-,2(#m "#m *-1m !0'12*#1Ym ',*+#,2#m 1#m .31-m #*m .#',#m #,m *m .02#m 13.#0'-0m "#*m %#*m .0m +0!0m #*m #1.!'-m "A,"#m 1#m !0%0>,m .-12#0'-0+#,2#m *1m +3#1201Ym ,m 4#8m .-*'+#0'8"-m#*m%#*m^#,20#mIFm7mJKm+',32-1_m1#m+-,2Am"#,20-m"#*mjmJIFFYm-"1m*1m .'#81m1#m#,!(0-,m2*m7m!-+-m+3#120m*m'%30mHYJYm#m31AmmGFm"'*3'"-mm.02'0m"#*m 12-!)m !-+#0!'*m ^m 3$$#0m !)Zm j_m !-+-m 2+.A,m .0m !-00#0m *1m +3#1201Ym 1m !-,"'!'-,#1m "#m .0#!*#,2+'#,2-m "#*m %#*m 31"1m #,m #*m jm JIFFm $3#0-,m *1m #12,"0'8"1m .0m #*m m /3#m !-00#1.-,"#,m m GKFFm Zm JFm +Zm JFm m 7m KFEm MK .,#&O3O'6.))- Detección e identificación de los mutantesO "30,2#mGKm+',32-1Ym,m4#8m&#!&-m#*m.0#!*#,2+'#,2-m"#*m%#*m1#m.0-!#"'Amm!0%0m*1m +3#1201Ym m m m (&30 TCMEOT#.0#1#,2!'A,m"#*m+-,2(#m,#!#10'-m.0m!-00#0m#*m%#*m#,m#*mjmJIFFYm*m%#*m1#m',20-"3!#m#,m*m +9/3',mjmJIFFm7m1#m!-,20-*m+#"',2#m3,m!-+.32"-0m /3#m!-,20-*m*1m!-,"'!'-,#1m "#m#*#!20-$-0#1'1m ^'+%#,m#620>"m"# 555Y*'!-0Y!-+_ m CMCMGMCTTTTTTTTTTT 1m +3#1201m !-,!#,20"1m +#"',2#m #*m *O 0m 1#m "#1,230*'80-,m #,m 3,m 2#0+-!'!*"-0m m OJEm "30,2#m Im +',32-1m #m ',+#"'2+#,2#m 1#m .31'#0-,m #,m &'#*-Ym *m +0!"-0m "#m MFFm . m ^jm '8#m 2,"0"m KFjMFFm .m 7#hm MFFm 7m NFF\_m .0m #*m j m 2+ '<,m "# >m "#1,230*'801#Ym 1m +3#120m 1#m !0%0-,m #,m 3,m .*!m "#m !0%m ^B@&&O',(O,3FODB@FOO"O&O)'*(3_m .0m 1>m .-12#0'-0+#,2#m 1-0 #0m *1m +3#1201m !-,m *-1m .#',#1m "#1#!& *#1m ^ B@O O "O &O )'*(3_Ym #1.3<1m "#m "-1m +',32-1m^#,m*-1m/3#m*m+3#120m1#m 1-0 #m '#,m#,m#*m.#',#_m1#m!-*-!Am#*m.#',#m#,m*m.02#m 13.#0'-0m "#*m %#*m 7m 1#m "#(0-,m !-00#0m *1m +3#1201m "30,2#m Jm +',32-1m !-,m #*m .#',#m #,!("-Ym ',*+#,2#Zm 1#m "#234-m #*m 4-*2(#m .0m /3'20m #*m .#',#m "#1#!& *#m "#(,"-m !-00#0m*1m+3#1201m#*m2'#+.-m,#!#10'-m#,m$3,!'A,m"#*m2+@-m"#*m+.*'!A,m^.0mGFFFm . ZmJjLm&-01_m^'%30mHYIY"_Ym m T ML Detección e identificación de los mutantes .,#&O3O'6.))- CMCMGMDTTTTTOTT -1m +32,2#1m 1#m '"#,2'$'!0-,m $',*+#,2#m #,m *-1m %#*#1m "#m !0'*+'"Ym 0m "#2#!20m 3,m +32,2#m&!#m$*2m&!#0m3,m,9*'1'1m"#2**"-m"#m*m'+%#,m#,m!"m!00'*m7m0#!-00#0*-m +,3*+#,2#m.0m.-"#0m"#2#!20m*-1m.#/3#@-1m.3,2-1m/3#m.0#!#,m!-+-m0#13*2"-m"#m *m"'%#12'A,m"#m3,m&#2#0-"B.*#6m!-,m*m#,8'+m()Ym 0m #*m ,9*'1'1m "#*m %#*m 1#m ,*'8Am *m '+%#,m ^!-,m *m 73"m "#*m .0-%0+m ").)")*_m +.*'9,"-*m &12m 0!0m 2-"-1m *-1m !00'*#1m .0m #,!-,200m *-1m !-02#1m "#m *-1m &#2#0-"B.*#6Ym m '+%#,m 1#m ,*'8Am !-,(3,2+#,2#m #,m *-1m "-1m !,*#1m ^MFFm 7m NFF_m 7m .-12#0'-0+#,2#m 1#m 4#0'$'!Am #,m !"m !,*m #*m .3,2-m "#m '"#,2'$'!!'A,m "#*m &#2#0-"B.*#6m !-+.0- 9,"-1#m /3#m *m 13+m "#*m 2+@-m "#*m !-02#m #,m *-1m "-1m !,*#1Zm !-',!'">m !-,m #*m 2+@-m2-2*m"#*m$0%+#,2-m,*'8"-m^'%30mHYK_Ym m m (&30 T CMF[m '13*'8!'A,m "#m *1m +3#1201m #,m #*m %#*m "#m Ym m "'%#12'A,m "#m 3,m &#2#0-"B.*#6m 1#m .3#"#m 4'13*'80m +#"',2#m "-1m .3,2-1m #,m #*m +'1+-m !,*Ym ,-m ^0-(-_m .#02#,#!#m *m $0%+#,2-m "'%#0'"-m "#1"#m #*m !# "-0m "'0#!2-m ^+0!"-m !-,m m MFF_m &12m #*m &#2#0-"B.*#6Zm 7m #*m -20-m $0%+#,2-m !-00#1.-,"#m "#1"#m #*m MM .,#&O3O'6.))- Detección e identificación de los mutantesO !# "-0m',4#01-m^+0!"-m!-,mmNFF_m&12m#*m&#2#0-"B.*#6Ym#m#12#m+-"-m*m13+m"#*m2+@-m"#m*-1m"-1m $0%+#,2-1m"# #m"0m#*m2-2*m"#*m2+@-m"#*m+.*'!A,Zm/3#m!-00#1.-,"#m*m&-+-"B.*#6m^ ,"m+0'**m"#m*m .02#m 13.#0'-0m "#*m %#*_Ym 0m 4'13*'80m !-,m +91m "#2**#m 7m 1#%300m *m #1.#!'$'!'""m "#*m !-02#m 1#m .3#"#m 4'13*'80m2+ '<,m#*m%#*m#,m!"m!,*m',"#.#,"'#,2#Zm#,m#12#m!1-m1A*-m4#0#+-1m#*m$0%+#,2-m+0!"-m.0m #1#m!,*m^'+9%#,#1m#,m *,!-m7m,#%0-mm*m"#0#!&_Ym m ,m4#8m'"#,2'$'!"-1m*-1m!00'*#1m/3#m!-,2#,>,m3,m"'%#12'A,m1#m.0-!#"'Am.0'+#0-mm*m '"#,2'$'!!'A,m"#*m.-!'**-m"#m*m.*!m+#8!*m7m.-12#0'-0+#,2#mm'"#,2'$'!0m*m$+'*'mHm !-,!0#2m /3#m !-,2#,>m *m +32!'A,m "#,20-m "#m *m +#8!*m ^0#!-0"#+-1m /3#m *1m +#8!*1m #129,m$-0+"-1m.-0m!320-m$+'*'1_Ymm#12#m.0-!#1-m1#m*#m**+m"#!-,4-*3!'A,Ym 0m*m"#!-,4-*3!'A,m1#m#* -0Am3,m.*,2'**m^'%30mHYL_m"A,"#m1#@*,"-m*m.-1'!'A,m "#*m .--*m +32,2#Zm 1#m .-">,m '"#,2'$'!0m !-,m 1#%30'""m *1m !320-m $+'*'1m Hm /3#m *-m $-0+ ,Zm%0!'1mm*m#1203!230m7mm*-1m!-*-0#1m"#m*m+'1+Ym ,m4#8m'"#,2'$'!"1m*1m!320-m$+'*'1m1#m0#.#2>m#*m.0-2-!-*-m^"#1"#m*m.0'+#0mZm -.O Zm $-0+!'A,m "#m &#2#0-"B.*#6Zm "'%#12'A,Zm .30'$'!!'A,Zm 7m %#*m "#m !0'*+'"_m .0m.-"#0m'"#,2'$'!0m!39*m"#m*1m!320-m$+'*'1mHm#0m*m/3#m!-,2#,>m*m+32!'A,Ymm m m (&30 T CMG[m *,2'**m "'1#@"m .0m -.2'+'80m *m "#!-,4-*3!'A,Ym 0'+#0-m 1#m +0!m *m .-1'!'A,m #,m *m .*!m "-,"#m 1#m &m "#2#!2"-m #*m .--*m +32,2#Ym + '<,m 1#m !-*-0#09m !-,m #*m !-*-0m !-00#1.-,"'#,2#m m *m .*!m .--*m "A,"#m&#+-1m#,!-,20"-m#*m+32,2#m^#,m#*m#(#+.*-m*m.-1'!'A,m"#*m+32,2#m"#2#!2"-m#1mJm"#m*m.*!m.--*mLm ^!-*-0m $3!1'__Ym -12#0'-0+#,2#m 1#m .0-!#"#m m '"#,2'$'!0m *m .*!m "'*3!'A,m "#m *m /3#m .0-4'#,#m #*m +32,2#[m "#1.*89,"-,-1mm*m"#0#!&m^$*#!&mGm%0'1_m"#1"#m,3#120-m#(#+.*-m^JZm$3!1'_m2#,#+-1m*m$'*m"#2#0+',"m7m ,-1m"#2#,"0#+-1m#,m*m!-*3+,m"#*m+'1+-m!-*-0mYm#m#12#m+-"-m.-"0#+-1m'"#,2'$'!0m*m.*!m"'*3!'A,m"-,"#m 1#m#,!3#,20m#*m+32,2#m^#,m#*m#(#+.*-m*m.*!m"'*3!'A,m#1m*mHHm^HH__Ym,m4#8m'"#,2'$'!"m*m.*!m"'*3!'A,m #1m,#!#10'-m'"#,2'$'!0m*m.-1'!'A,m"#m*1m!320-m$+'*'1m/3#m!-+.-,#,m#*m.--*m#,m*m.*!m"'*3!'A,Ym0m#**-Zm 32'*'8+-1m *m $*#!&m Hm 7m ,-1m "#1.*8+-1m m *m '8/3'#0"m "#1"#m *m *-!*'8!'A,m "#m ,3#120-m +32,2#Ym ,+#"'2+#,2#m1 #+-1m/3#m*1m$+'*'1m/3#m!-+.-,#,m#*m.--*m+32,2#m#129,m#,m*1m.-1'!'-,#1m^jjj_m ^%0!'1mm*m$*#!&mH_m"#m*m!-*3+,mJm"#m*m.*!m"#m"'*3!'A,mHHYm T T T MN Detección e identificación de los mutantes .,#&O3O'6.))- CMCMHTTTTTTT 0m '"#,2'$'!0m #*m !+ '-m "#m 1#m .0-"3!'"-m .-0m #*m m &'8-m $*2m 1#!3#,!'0m *1m $+'*'1mHm+32,2#1Ym0m#**-m1#m+.*'$'!Am+#"',2#m-.O-Om"#m*1m$+'*'1m +32,2#1m"#m!"m%#,m,*'8"-Ymm+.*'$'!!'A,m1#m!-+.0- Am+#"',2#m%#*m"#m%0-1m 7m #*m $0%+#,2-m 1#m .30'$'!Am +#"',2#m #.&"#6Ym 0m *m 1#!3#,!'!'A,m 1#m 32'*'8Am #*m .0-2-!-*-m"#1!0'2-m#,m#*m.02"-m,2#0'-0m^HYHYGYH_Ym ,m 4#8m - 2#,'"1m *1m 1#!3#,!'1m 1#m ,*'80-,m !-,m #*m .0-%0+m +/(",O >EAm 7m 1#m 31!Am #,m #*m !0-+2-%0+m *m +32!'A,m #,m $-0+m "#m "- *#m .'!-m ^7m /3#m !"m $+'*'m !-,2'#,#m 1m "#m GFm ',"'4'"3-1m 7m #,m !-,1#!3#,!'m 1#m 202m "#m 3,m +#8!*m "#m *#*-1m +32,2#1m 7m 1'*4#120#1_Ym ,m 4#8m "#2#!2"m *m +32!'A,m 1#m ,*'8Am !-,m #*m +'1+-m .0-%0+m1'm*m+32!'A,m#12 m*-!*'8"m#,m8-,m',20A,'!m-m#6A,'!m7m#,m#12#mB*2'+-m !1-m 1'm !-+.-02 m 3,m !+ '-m "#m +',-9!'"-Ym 0m #**-Zm 1#m 20"3(-m *m 1#!3#,!'m - 2#,'"m"#*m+32,2#m7m1#m!-+.0Am!-,m*m1#!3#,!'m"#m*m.0-2#>,m-0'%',*Ym1>m1#m.3"-m 4#0'$'!0m 1'm & >m 3,m !+ '-m "#m +',-9!'"-m 7m !A+-m "#m "0912'!-m .-">m 1#0m #*m !+ '-m +#"',2#m,9*'1'1m!-,m#*m.0-%0+mYm m CMCMIT T T T T T T T T T TT 12m.02#m"#*m.0-2-!-*-m1A*-m.3"-m0#*'801#m!-,m*-1m+32,2#1m"#m*m'2-#,-m"#12301Ym ',m#+ 0%-Zm20 (-1m.-12#0'-0#1m0#*'8"-1m.-0m-20-1m!-* -0"-0#1m"#*m* -02-0'-m&,m .#0+'2'"-m/3#m2#,%+-1m"2-1m"#m1#%0#%!'A,m"#m-20-1m+32,2#1m"#*m%#,m>m^<12-1m1#m .0#1#,20,m.-12#0'-0+#,2#m#,m#*m.02"-mJYHYH_Ym ,m 4#8m '"#,2'$'!"m *m $+'*'m Hm +32,2#m 1#m %#0+',0-,m HKm 1#+'**1m "#m *m +'1+m $+'*'m ^.0-.-0!'-,"1m .-0m jZm *#,!'Zm "-,"#m 1#m &**,m *+!#,"1_Ym 121m 1#m %#0+',0-,m .0m - 1#040m 1#%0#%!'A,m "#m *m +32!'A,m 7m *%B,m $#,-2'.-Ym ,m #12"'-m"#m.*9,23*m1#m.0-!#"'Amm&!#0m3,m#620!!'A,m"#mm"#m*1m.*,21m+32,2#1m .0m*mm1#%B,m#*m.0-2-!-*-m"#1!0'2-m#,m#*m.02"-mHYGYIYHm.0m.-"#0m1#!3#,!'0m7m ,*'80m ^1#%B,m .02"-m HYHYGYH_m *m 0#%'A,m "-,"#m 1#m #,!-,20 m *m +32!'A,Zm 7m "#m #12#m +-"-m !-+.0- 0m /3#m & >m 1#%0#%!'A,m "#*m *#*-m +32,2#m #m '"#,2'$'!0m 3,m ',"'4'"3-m !-,m#*m*#*-m+32,2#m#,m&-+-8'%-1'1Ymm m MO .,#&O3O'6.))- EcoTILLING CMDTT T CMDMBTTTT 0m#*m!-m1#m.0#.0Am#*mm"#mGGIm40'#""#1m"#m+#*A,m/3#m1#m0#!' '#0-,m "#*m ,!-m "#m %#0+-.*1+m "#*m m ^,#6-m Y(_Ym #m !"m 3,-m "#m #**-1m 1#m &'8-m *m !3,2'$'!!'A,m +#"',2#m ,-"0-.m ^(),)*LO *.,)*").)'.,O N;E:::_Ym ,m 4#8m "#2#0+',"m *m !-,!#,20!'A,m "#m m "#m !"m 40'#""Zm 1#m "'*37Am m KFm ,%ix*m 7m 1#m @"'Am #*m 4-*3+#,m "#!3"-m "#m m "#m LHjGGIm ^m "#m 0#$#0#,!'_m .0m - 2#,#0m 3,m+#8!*m#/3'+-*0m#,m*m/3#m+ -1m1m#1234'#0,mmKFm,%ix*Ym #m"'1#@Am3,m.*!m"-,"#m!"m.-!'**-m!-,2#,>m*m+#8!*m"#m*1m"'$#0#,2#1m40'#""#1m "#m+#*A,m!-,m#*mm"#m0#$#0#,!'Ym0m"#2#0+',0m*1m"'$#0#,!'1m*<*'!1m^&.*-2'.-1_m #,20#m*1m40'#""#1m1#m0#*'8Am#*m.0-2-!-*-m"#mm!-,m*-1m%#,#1m>m7m;Em,m *-1m %#*#1m "#m !0'*+'"m 7m *1m 1#!3#,!'!'-,#1m .-12#0'-0#1m 1#m .3"'#0-,m '"#,2'$'!0m *-1m "'12',2-1m&.*-2'.-1m.0m!"m%#,Ym m CMDMCTTTTT 0m *m "#2#0+',!'A,m "#m *-1m &.*-2'.-1m 1#m 1#*#!!'-,0-,m *1m 40'#""#1m /3#m .0#1#,2 ,m &#2#0-"B.*#6m #,m *-1m %#*#1m 7m 1#m 1#!3#,!'0-,m !-,m #*m +'1+-m .0-2-!-*-m ',"'!"-m ,2#0'-0+#,2#Ym ,m 4#8m - 2#,'"1m *1m 1#!3#,!'1m 1#m ,*'80-,m !-,m #*m .0-%0+m +/(",O >EAm 7m 1#m '"#,2'$'!0-,m *-1m &.*-2'.-1m "'4#0%#,2#1m m *m 40'#""m 0#$#0#,!'Ym ',*+#,2#Zm 1#m !-+.00-,m *-1m "2-1m $#,-2>.'!-1m .0-!#"#,2#1m "#*m m .0m !"m 40'#""m !-,m *-1m &.*-2'.-1m .0m ',2#,20m "#2#0+',0m 1'm #6'12>m *%3,m !-00#*!'A,m#,20#m*m$3,!'A,m"#*m%#,mm7m13m$#,-2'.-Ymm T NF ,).))&)-O!(,&- .,#&O3O'6.))-OO m TOTTTT -1m .0-2-!-*-1m "#1!0'2-1m m !-,2',3!'A,m &,m 1'"-m 32'*'8"-1m $0#!3#,2#+#,2#m "30,2#m #*m .#0>-"-m "#m #12m 2#1'1m 3,/3#m ,-m #129,m "'0#!2+#,2#m 0#*!'-,"-1m !-,m #*m .0-2-!-*-m "#m Y TT CMETTTTT #m 310-,m ,3#1201m "#m .3*.m "#m $032-m "#m +#*A,m GGGm GKm ">1m 7m JLm ">1m .-12,2#1'1Ym *m .0-2-!-*-m32'*'8"-m!-00#1.-,"#m*mjm^_Ym #m2-+0-,mHm%m"#m!"m+3#120m"#m.3*.m7m1#m.3*4#0'80-,m!-,m,'20A%#,-m*>/3'"-m#,m3,m +-02#0-m .0#4'+#,2#m #12#0'*'8"-Ym ,m 4#8m .3*4#0'8"-Zm #*m +2#0'*m 1#m 20,1$'0'Am m 3,m 23 -m*!-,m"#mKFm+*m7m1#m*#m@"'AmHFm+*m"#mjYm-12#0'-0+#,2#m1#m0#.02'Am *m+#8!*m#,m.02#1m'%3*#1m#,m23 -1m*!-,m"#mKFm+*Zm7m1#m*#1m@"'Am-20m4#8mm!"m3,-m FZHm+*m.-0m+*m"#m4-*3+#,m"#mjYm#m%'2Am7m1#m!#,20'$3%Am*m+#8!*mmIYFFFm 0.+m"30,2#mJKm+',32-1mmJEYm-12#0'-0+#,2#m1#m0#!3.#0Am*m$1#m!3-1m7m1#m0#.02'Am #,m 23 -1m #.#,"-0$m "#m GZKm +*m @"'<,"-*#m m !"m 3,-m FZKm +*m "#m '1-.0-.,-*m !#,20'$3%9,"-*-1m m NYFFFm 0.+m "30,2#m IFm +',32-1m m JEYm #m #12#m +-"-m 1#m - 234-m 3,m .#*#2Zm /3#m 1#m "#(Am 1#!0m #,20#m GFjGKm +',32-1m m 2#+.#0230m + '#,2#m .0m .-12#0'-0+#,2#m 0#131.#,"#0*-m !-,m HFm x*m "#m %3Ym m !-+.0- !'A,m "#m *m !,2'""m 7m !*'""m "#*m m 1#m &'8-m +#"',2#m %#*m "#m %0-1Ym 0#4'+#,2#m 1#m &'!'#0-,m 40'-1m *4"-1m"#mm^G_m*m+2#0'*m"#m#*#!20-$-0#1'1m.0m#4'20m*m!!'A,m"#m11Ym T CMFTTTTT T CMFMBTTP$$$QT ,m4#8m'"#,2'$'!"-m3,m.-*'+-0$'1+-m#,m3,m1#!3#,!'m.3#"#m,*'801#m1'm#,m<*m#6'12#m *%3,m"',m"#m#,8'+m"#m0#120'!!'A,Ym#m#12#m+-"-Zm1'm1#m0#*'8m*m+.*'$'!!'A,m"#*m $0%+#,2-m 7m .-12#0'-0+#,2#Zm *m "'%#12'A,Zm #*m .20A,m - 2#,'"-m 1#09m "'12',2-m #,20#m #*m %#,-2'.-m /3#m 2'#,#m #*m .-*'+-0$'1+-m 7m #*m /3#m ,-Ym 12m "'$#0#,!'m "#m .20A,m 1#m .-"09m 4'13*'80m #,m 3,m %#*m "#m %0-1m ^-,'#!8,7m 7m 313 #*Zm GOOI_Ym m !-,!#,20!'A,m "#m %0-1m"#m#12-1m%#*#1m"#.#,"#09m"#*m2+@-m#1.#0"-m"#m*-1m$0%+#,2-1m"#m"'%#12'A,Ym m +#,-0m 2+@-m "#m $0%+#,2-Zm +91m "#,1'""m "# #m 2#,#0m #*m %#*Zm **#%,"-m m 3101#m ,-0+*+#,2#m%#*#1m"#m%0-1m*mHPYm,m4#8m+.*'$'!"1m*1m0#%'-,#1m"#*m$0%+#,2-m NG .,#&O3O'6.))- ,).))&)-O!(,&-O ,*'8"-Zm1#m.0-!#"#mm.0#.00m*1m"'%#12'-,#1m!-,m*1m#,8'+1m"#m0#120'!!'A,Ym121m1#m 0#*'80-,m & '23*+#,2#m #,m 3,m 4-*3+#,m 2-2*m "#m HFm x*m /3#m !-,2'#,#,m Hm x*m "#m 2+.A,m GF6m^!-00#1.-,"'#,2#mm!"m#,8'+m"#m0#120'!!'A,_ZmHYKmm"#m#,8'+ZmGFmx*m"#*m.0-"3!2-m +.*'$'!"-Ymm+#8!*m1#m',!3 mm*m2#+.#0230mA.2'+m"#m!"m#,8'+m^IMEjLKE_m "30,2#m Hm &m ^2+ '<,m 40' *#m #,m $3,!'A,m "#m *m #,8'+_Ym *m .0-"3!2-m "#m "'%#12'A,m 1#m 4'13*'8m201m#*#!20-$-0#1'1m#,m%0-1YT T CMFMCTTT1TP$$ QT *m .0-2-!-*-m 31"-m #,m #*m * -02-0'-m .0m *m +.*'$'!!'A,m "#m +0!"-0#1m 1m #12 m .3#12-m m .3,2-m !-,m +0!(#m 0"'-!2'4-m ^28'0m 7m !-*YZm GOOL_Ym 0m *m 0#!!'A,m "#m +.*'$'!!'A,m 1#m 31Am #*m 2+.A,m "#m m G6m ^0'1j*m MKm +m .m NYNZm ^J_Hm HFm Zm 5##,jHFmFYFGmP_Zm%*HmIYKm+ZmFYLmxm"#m!"m!# "-0m^"#.#,"'#,"-m"#*m_ZmGLLm xm "#m ,3!*#A2'"-1m "Zm "Zm "Zm Hm xm "Zm FYGm x*m "#m tIIm j"m ^IYFFFm 'i++-*_ZmHmm+m.-*'+#01m7mLFm+%m"#mm+-*"#m#,m3,m4-*3+#,m2-2*m"#mGKmx*Ym1m !-,"'!'-,#1m "#m +.*'$'!!'A,m $3#0-,m 3,m .0'+#0m !'!*-m "#m "#1,230*'8!'A,m m OJEm "30,2#m Gm +',Zm .-12#0'-0+#,2#m IKm !'!*-1m "#m +.*'$'!!'A,m "#m IFm 1m m OJm EZm IFm 1m "#m &' 0'"!'A,m m KOEm 7m IFm 1m "#m #*-,%!'A,m m MHEm 7m .-0m B*2'+-Zm 3,m #62#,1'A,m $',*m "#m Km +',mmMHEYm -12#0'-0+#,2#m m *m +3#120m 1#m *#m @"'Am GFm x*m "#m 2+.A,m "#m !0%m ^OKPm $-0++'"Zm m GFm +Zm 83*m "#m 0-+-$#,-*m FYFGm PZm 6'*#,!',-*m FYFGP_Ym 1m +3#1201m $3#0-,m "#1,230*'8"1m "30,2#m GFm +',32-1m m GFFEm .0m .-"#0m .0-!#"#0m m *m 1#.0!'A,m +#"',2#m#*#!20-$-0#1'1m4#02'!*m#,m!-,"'!'-,#1m"#1,230*'8,2#1m#,m%#*#1m"#m!0'*+'"m "30,2#mHjIm&-01Ym #1.3<1m "#m @"'0*#m m *m +3#120m #*m 2+.A,m "#m !0%m 7m .*'!0*#m #*m .0-!#1-m "#m "#1,230*'8!'A,Zm 1#m !0%0-,m Jm x*m "#m *-1m .0-"3!2-1m "#m +.*'$'!!'A,m #,m #*m %#*m "#m !0'*+'"Ym*m!-,2#,'"-m"#m!0'*+'"m32'*'8"-m.0m*-1m1m#1m& '23*+#,2#m"#m3,m LPm "#m !0'*+'"m ^GO[Gm !0'*+'"i '1!0'*+'"_Zm 2+.A,m m G6Zm 30#m MYKm Zm FYFKPm m ^.#013*$2-m "#m +-,'-_m 7m FYGPm m ^ZZaZaj#20+#2&7*#,#"'+',_Ym ,m 4#8m .-*'+#0'8"-m #*m %#*Zm 1#m !*#,2Am &12m *!,80m *-1m KFEm .0m .-12#0'-0+#,2#m !0%0m *1m+3#1201m7m.*'!0m3,m4-*2(#m"#mLFmm"30,2#mHjIm&-01Ym #1.3<1m#*m%#*m$3#m20,1$#0'"-mm3,m..#*m&2+,mImZm1#!"-m*m4!>-m7m#6.3#12-m #,m3,m$'*+m$-2-%09$'!-mm30'6mHm&12m#*m">m1'%3'#,2#Ym m T NH ,).))&)-O!(,&- .,#&O3O'6.))-OO CMFMDTTT1TTTTTT 12m 2<!,'!m 1#m 1m #,m #*m .0-2-!-*-m "#*m '2m !-+#0!'*m m 0'1+m 1&-2m ""m 0'+#0m62#,1'-,m'2m^..*'#"m'-1712#+1_Ym-0+*+#,2#m$3#m31"m#,m*-1m!1-1m#,m/3#m ,-m 1#m "#2#!2 m ,',%3,m #,8'+m "#m 0#120'!!'A,m /3#m .3"'#1#m "'$#0#,!'0m + -1m *#*-1m .0m "'1#@0m 3,m +0!"-0m 2'.-m Ym 0m ','!'0m #*m .0-2-!-*-m "# >m - 2#,#01#m #*m .0-"3!2-m "#m m !-,m *-1m !# "-0#1m #1.#!>$'!-1m m 7m !-+.0- 0m *m !,2'""m 1>m !-+-m *m !*'""m "#m *m +.*'$'!!'A,Ym 0m #12#m .0-2-!-*-m #0m ,#!#10'-m "'1#@0m 3,m !# "-0m ',2#0,-m "#m 3,1m HFm . m /3#m 2#0+',0m *m .-1'!'A,m Iam (312-m ,2#1m "#*m ,3!*#A2'"-m .-*'+A0$'!-Ymm #m 2-+0-,m KFm ,%m "#*m .0-"3!2-m +.*'$'!"-m 7m 1#m *#m @"'#0-,m Hm x*m "#m *m #,8'+m 6-j jm^Zm*#4#*,"Zm&'-_m.0m',!3 0m*m+#8!*m"30,2#mGKm+',32-1mmIMmEYmm12m #,8'+m !-,2'#,#m 3,m #6-,3!*#1m m 7m 3,m $-1$21m *!*',m "#m %+ m /3#m 1-,m &'"0-*>2'!1m 7m 1#m 32'*'8,m .0m #*'+',0m *-1m 0#12-1m "#m "1m 7m !# "-0#1m /3#m /3#",m "#1.3<1m "#m 0#*'80m *m Zm "#m +-"-m /3#m ,-m .3#",m ',2#0$#0'0m #,m *-1m .1-1m 1'%3'#,2#1m "#*m.0-2-!-*-Ym-12#0'-0+#,2#m1#m',!2'4Am*m#,8'+mmNFmEm"30,2#mGKm+',32-1Ymm #m#12m0#!!'A,m1#m32'*'80-,mHKm,%m!-+-m+-*"#m.0m*m#62#,1'A,Zm(3,2+#,2#m!-,mHYKm x*m "#m ,1&-2m #"7m #!2'-,m '6m 7m Hm .+-*m "#*m !# "-0m ',2#0,-m .0#4'+#,2#m "'1#@"-Zm#,m3,m4-*3+#,m2-2*m"#mKmx*Ymm0#!!'A,m"#m#62#,1'A,m!-,1'12'Am#,mHKm!'!*-1m"#m 3,m.0'+#0m"#1,230*'8!'A,mmOLEm"30,2#mGFm1Zm*m&' 0'"!'A,m"#*m!# "-0m',2#0,-mm KFEm"30,2#mIFm1m7m*m#62#,1'A,mmLFEm"30,2#mIFm1Ym',*+#,2#m1#m+,234-m*m0#!!'A,m mJmEYm-12#0'-0+#,2#m1#m202Am*m0#!!'A,m!-,mGmm"#m$-1$21m',2#12',*m -4',m^-!&#_m mIMEm"30,2#mGm&Zm.0m"#%0"0m#*m!# "-0m',2#0,-m/3#m.3"'#0m/3#"0m#,m#6!#1-Ym#m ',!2'4Am*m#,8'+m**#4,"-m*m0#!!'A,mmMKEm"30,2#mGKm+',Ym3#%-m1#m@"'AmKFFm !-+-m +0!"-0m "#m .#1-m +-*#!3*0Ym *m !# "-0m #62#,"'"-m 1#m 4'13*'8Am #,m 3,m 1#!3#,!'"-0mm0'1+mIGFFm^..*'#"m'-1712#+1_m#,m*1m!-,"'!'-,#1m0#!-+#,""1m#,m #*m.0-2-!-*-m"#m1&-2Ym m CMGT TTT 0m #*m !*-,(#m "#m m #,m .*91+'"-m 1#m 32'*'80-,m *1m !#.1m "#m EO )&#m m GFOm !-+.#2#,2#1m .-0m !&-/3#m 2<0+'!-m /3#m 4#,>,m "(3,21m *m '2m "#*m 4#!2-0m "#m !*-,(#m .jm b17m #!2-0m 712#+cm ^0-+#%_Ym 0m ','!'0m #*m !*-,(#m 1#m +.*'$'!Am #*m $0%+#,2-m#,m!3#12'A,m+#"',2#mYm-1m!# "-0#1m32'*'8"-1m$3#0-,m#,m!"m!1-m*-1m #1.#!>$'!-1m"#m*m0#%'A,mm+.*'$'!0Ym-12#0'-0+#,2#m1#m234-m/3#m.30'$'!0m#*m$0%+#,2-m "#m m +#"',2#m #*m '2m !-+#0!'*m -!&#m ^#!"O/,OO,)/.O/,# #.#)(O#._Ym ,m NI .,#&O3O'6.))- ,).))&)-O!(,&-O 4#8m &#!&m *m !-+.0- !'A,m "#m *m !*'""m 7m !,2'""m "#*m .0-"3!2-m +#"',2#m %#*m "#m %0-1Zm 1#m 0#*'8Am *m *'%!'A,m 2*m 7m !-+-m ',"'!m #*m $ 0'!,2#m "#*m '2m .jm 17m #!2-0m712#+mYm-12#0'-0+#,2#m1#m0#*'8Am*m20,1$-0+!'A,m#,m*1m!<*3*1m!-+.#2#,2#1m mGFOm/3#m2+ '<,m',!*3>m#*m'2m!-+#0!'*Ym CMGMBT T T T T T T T ,20#mGjImx*m"#m*m0#!!'A,m"#m*'%!'A,m$3#m@"'"mmKFmx*m"#m!<*3*1m!-+.#2#,2#1m/3#m #1234'#0-,m.0#4'+#,2#m',!3 "1m#,m&'#*-m"30,2#mIFm+',Ym*m!&-/3#m2<0+'!-m1#m0#*'8Am mJHEm"30,2#m.0-6'+"+#,2#mKFm1m7m09.'"+#,2#m1#m',!3 Am#,m&'#*-m"30,2#mHm+',Ym 3#%-m 1#m 20,1$'0'#0-,m *1m !<*3*1m m 3,m 23 -m #.#,"-0$m !-,m OKFm x*m "#m m ^GPm !2-j 20'.2-,ZmFYKmPm#620!2-m"#m*#4"30ZmFYKmPm*m.mMYF_m.0m',!3 0*1m"30,2#mGm&mm IMEm7m!-,m3,m%'2!'A,m"#mHFFm0.+Ym 1m!<*3*1m20,1$-0+"1m$3#0-,m1#*#!!'-,"1m#,m.*!1mm%0m^ZmGYKmPm !2-j%0_m !-,m,2' 'A2'!-m"#m0#1'12#,!'m+.'!'*',m^KFmx%i+_Zmj*m^Kj 0-+-jJj!&*-0-jIj',"-*'*jm uj%*!2-1'"1_m ^HFm ,%i+_m #m m ^'1-.0-.'*2'-jm ujm j%*!2-1'"1_m ^JFm x%i+_Ym 1m .*!1m 1#m "#(0-,m ',!3 0m 2-"m 3,m ,-!&#m m IMEm .0m .-"#0m 1#*#!!'-,0m *1m !<*3*1m 20,1$-0+"1Ym m CMGMCTTTTTPQT 0m *m .30'$'!!'A,m "#*m m .*1+>"'!-m 1#m 31Am #*m '2m '%#,hm ','.0#.m ^'%#,_Zm 1"-m#,m*m*'1'1m*!*',m"#m*1m!<*3*1m !2#0',1m^'0, -+m7m-*7ZmGOMO_m!-,m*%3,m +-"'$'!!'A,Ymm#m32'*'80-,mGZKm+m"#m!3*2'4-m !2#0',-m/3#m1#m& >m!0#!'"-m"30,2#m 2-"m*m,-!&#m,2#0'-0mmIMEYm-12#0'-0+#,2#Zm1#m!#,20'$3%AmmNYFFFm0.+m"30,2#mIm+',m "#m +-"-m /3#m #*m .0#!'.'2"-m $3#m 0#131.#,"'"-m !-,m *m 1-*3!'A,m m (3,2-m !-,m 1m ^GFFm x%i+_Ym -12#0'-0+#,2#m 1#m @"'#0-,m JFFm x*m "#m *m 1-*3!'A,m m ^/3#m .0-"3!#m *m *'1'1m !#*3*0_m 7m 1#m ',!3 Am #,m &'#*-m "30,2#m Km +',m !-,m 3,m 0#4#m %'2!'A,m .0m ,-m "@0m #*m m .*1+>"'!-Ym *m @"'0m IFFm x*m "#m 1-*3!'A,m m 1#m ,#320*'8Am *m m *'1'1m ^.3#12-m /3#m !-,2'#,#m3,m*2m!-,!#,20!'A,m"#m1*#1m7m#121m.#0+'2#,m*m0#,230*'8!'A,m"#*mm .*1+>"'!-m7m13m#12 '*'8!'A,m#,m*m1-*3!'A,_Ym#1.3<1m3,m!#,20'$3%!'A,mmGIYFFFm0.+m "30,2#m Mm +',m m Jm Em .#0+'2'Am *m .0#!'.'2!'A,m "#m *-1m 0#12-1m !#*3*0#1Ym *m m .*1+>"'!-m !-,2#,'"-m #,m #*m 1- 0#,",2#m 1#m 20,1$'0'Am m 3,m 23 -m ,3#4-m #4'2,"-m #*m .0#!'.'2"-Ym#m*#m@"'Am3,m4-*3+#,m"#m$#,-*j!*-0-$-0+-m7m1#m!#,20'$3%Am"30,2#mKm+',m m GIYFFFm 0.+Ym #m 0#!3.#0Am *m $1#m !3-1m @"'<,"-*#m KFFm x*m "#m '1-.0-.,-*m 7m NJ ,).))&)-O!(,&- .,#&O3O'6.))-OO +#8!*9,"-*-m '#,m.-0m',4#01'A,Ym#m!#,20'$3%AmGFm+',mmGIYFFFm0.+m7m1#m*'+.'Am#*m.#*#2m - 2#,'"-Ym ',*+#,2#m 1#m *4Am #*m .#*#2m !-,m #2,-*m *m MFPm !#,20'$3%9,"-*-m 2+ '<,m "30,2#mKm+',mmGIYFFFm0.+Ym3#%-m1#m"#(Am1#!0m#*m.#*#2m7m1#m0#131.#,"'Am#,mKFmx*m"#m %3m"#1'-,'8"m#12<0'*m- 2#,'#,"-m3,m0#,"'+'#,2-m"#mGjJmx%m"#mm.-0mGZKm+m"#m !3*2'4-Ym m T NK )(-.,/#9(OO/(O*&. ),'OO Resultados m m NL m )(-.,/#9(OO/(O*&. ),'OO Resultados m DMTT T T DMBT T T T T T T T Tm 30,2#m *-1m B*2'+-1m @-1m *m 2<!,'!m "#*m m 1#m &m 31"-m +.*'+#,2#m .0m #*m .-7-m "#m *m +#(-0m %#,<2'!m #,m .*,21m ^,%Zm HFFL_Zm 3,/3#m #,m +#*A,m 2-"4>m ,-m 1#m & >m "#100-**"-m ,',%3,m .- *!'A,m "#m +32,2#1Ym +.0#11m .0'4"1m !-+-m '#&&-O #.9m1#m& >,m+-120"-m',2#0#1"1m#,m73"0mm"#100-**0m&#00+'#,21m/3#m73"0,m m -.2'+'80m *m 1#*#!!'A,m 7m +#(-0m "#m #12m #1.#!'#Ym *m "#100-**-m "#m 3,m .*2$-0+m "#m +32,2#1m0#.0#1#,20>m3,m!-*#!!'A,m"#m',"'4'"3-1m!-,m,3#4-1m*#*-1m/3#m.-"0>,Zm#,m *%3,-1m!1-1Zm.0-.-0!'-,0m,3#4-1m!0!2#0#1m"#m',2#0<1m.0m*m#1.#!'#Ymm/3#m/3>m1#m "#1!0' #m #1m *m .0'+#0m .- *!'A,m "#m m #* -0"m #,m //'#-O '&)m ^3,/3#m "30,2#m*-1m!320-m@-1m"#m#12#m20 (-m7m1#m&m- 2#,'"-m-20m^&+,'j0"1m7m!-*YZm HFGF__Zm /3#m &m 0#/3#0'"-m 3,m *0%-m .0-!#1-m "#m .3#12m m .3,2-m 7m -.2'+'8!'A,m "#*m .0-2-!-*-Ym 12#m 20 (-m 1#m #,!3#,20m #,+0!"-m "#,20-m "#*m .0-7#!2-m m ^HFGIjHFHIMZm HFFJjHFFM_m /3#m 2#,>m !-+-m - (#2'4-m "#100-**0m &#00+'#,21m %#,A+'!1m.0m#*m+#*A,m7m/3#m!-,2Am!-,m*m!-* -0!'A,m"#m*m#+.0#1m'#&&-O#.9m7m#*m m^,12'232-m"#m-,1#04!'A,m7m#(-0m"#m*m%0-"'4#01'""m*#,!',_m.0m*m .3#12mm.3,2-m"#m*m.*2$-0+m"#mYm m DMBMBTTTTTTT DMBMBMBTTTTTTTTGCSBBDT 0m"#100-**0m*m.- *!'A,m"#mm#,m+#*A,m1#m"#!'"'Am310m*m*>,#m.30m"- *#m &.*-'"#m ^_m "#m +#*A,m 2'.-m b'#*m "#m 1.-cm 40'#""m ()),/-m LHjGGIYm m #+.0#1m '#&&-O#.9O$3#m*m#,!0%"m"#m13 +','1200m*1m1#+'**1m"#m#12m*>,#m.0m%#,#00m*m .- *!'A,m"#mYm 0m !-00- -00m /3#m *m *>,#m #0m 0#*+#,2#m &-+-!'%-2Zm 1#m ,*'8Am !-,m 3,m 2#0>m "#m +'!0-12<*'2#1m ^1_m 2,2-m *m *>,#m -0'%',*m LHjGGIm !A+-m *1m*>,#1m .0#,2*#1m 31"1m $0#!3#,2#+#,2#m#,m#*m* -02-0'-Zm*m*>,#mb'#*m"#m.-cmGGGm7m*m!!#1'A,m!-0#,mm GLGIMKYm ,*'8,"-m Hm 1m .-0m %03.-m "#m *'%+#,2-m ^ *m IYGm 7m '%30m IYG_m *-1m 0#13*2"-1m +-1200-,m /3#m #*m %#,-2'.-m "#m *m *>,#m 31"m #0m '%3*m /3#m #*m %#,-2'.-m "#m NM )(-.,/#9(OO/(O*&. ),'OO Resultados GGGZm 7m "'12',2-m "#*m m 7m m 13m 4#8Zm .3"'+-1m !-,$'0+0m /3#m #0m &-+-!'%-2m .0m *-1m HJm 1m#,17"-1Ym m T !+ TDMB[m#1!0'.!'A,m"#m*-1m1m32'*'8"-1m.0m*m!-+.0- !'A,m"#m*m&-+-!'%-1'1m"#m*m*>,#mLHjGGIYmm m -+ 0#m +0!"-0m m m NKm NKm m Jm Jm m IOm IOm m LNm LNm m IFm IFm m GHKm GHKm m GFNm GFNm m Lm Lm m KHm KHm m Hm Hm m GNm GNm m JGm JGm m m NN m m # "-0m"'0#!2-i0#4#01-m #$#0#,!'m iLHj GGIm m #0,9,"#8j '*4m7m!-*YZm HFFNm GFMm GGFgm -,8*-m7m!-*YZm HFFKm GHLm GIFm -m.3 *'!"-m GJFm GLFm -,8*-m7m!-*YZm HFFKm GNFm GOKm -,8*-m7m!-*YZm HFFKm GMNm GKFgm #0,9,"#8j '*4m7m!-*YZm HFFNm GIKm GGFgm #0,9,"#8mj '*4m7m!-*YZm HFFNm GGIm GHFgm -,8*-m7m!-*YZm HFFKm GJFm GKFm -,8*-m7m!-*YZm HFFKm GHFm GJFm -,8*-m7m!-*YZm HFFKm GLKm GMKm -,8*-m7m!-*YZm HFFKm GJFm HGFm -,8*-m7m!-*YZm HFFKm GHFm GJKm m m m m m m m m m m m m m m m m m m m m m m m m m +@-m*#*-1m ^. _m m m m )(-.,/#9(OO/(O*&. ),'OO m MKm MKm m GMHm GMHm m Hm Hm m KKm KKm m JMm JMm m HHm HHm m MGm MGm m Nm Nm m LIm LIm m NOm NOm m HOm HOm m IIm IIm Resultados m m m m m m m m m m m m m m m m m m m m m m m m -,8*-m7m!-*YZm HFFKm GKFm GMKm #0,9,"#8j '*4m7m!-*YZm HFFNm GGGm GIFgm -,8*-m7m!-*YZm HFFKm GKHm GJFgm #0,9,"#8j '*4m7m!-*YZm HFFNm GGGm GHFgm ,',j-*#%m7m !-*YZmHFFFm GKJm GJKgm -,8*-m7m!-*YZm HFFKm GLLm GMFm -,8*-m7m!-*YZm HFFKm GLKm HFKm -,8*-m7m!-*YZm HFFKm GJFm GKKm #0,9,"#8j '*4m7m!-*YZm HFFNm GFFm GIFgm -,8*-m7m!-*YZm HFFKm GINm GMKm -,8*-m7m!-*YZm HFFKm GIMm GHFgm -,8*-m7m!-*YZm HFFKm GGFm GHKm m [email protected]'+"-m"#2#0+',"-m+#"',2#m4'13*'8!'A,m"#m*-1m%#*#1Ymm m m m m NO Resultados )(-.,/#9(OO/(O*&. ),'OO m m (&30 T DMB[m -1'!'A,m "#m *-1m 1m ,*'8"-1m #,m *m *>,#m LHjGGIm #,m !"m %03.-m "#m *'%+'#,2-m "#*m +.m %#,<2'!-m"#m+#*A,mm^#0,9,"#8j'*4m7m!-*YZmHFFN_Ymm DMBMBMCTTTTTTTTT ,-m "#m *-1m - (#2'4-1m +91m '+.-02,2#1m .0m "#100-**0m 3,m .- *!'A,m "#m m #$#!2'4m#1m/3#m2#,%m3,m#*#4"m21m"#m+32!'A,Ym0m#**-Zm&!#m$*2m#12 *#!#0m!39*m #1m#*m0,%-m"#m"-1'1m"#m+329%#,-m+91m"#!3"-m.0m- 2#,#0m3,m*2m21m"#m+32!'A,m OF )(-.,/#9(OO/(O*&. ),'OO Resultados !-+.2' *#m!-,m3,m 3#,m21m"#m13.#04'4#,!'m7m$#02'*'""m"#m*1m.*,21m^',)*#0m7m !-*YZm HFFK_Ym ,m ,3#120-m * -02-0'-m 1#m 0#*'8Am 3,m #6.#0'+#,2-m .0#4'-m *m "#100-**-m "#m *m .- *!'A,m "#m m .0m .-"#0m #12 *#!#0m #*m 0,%-m "#m "-1'1m +91m "#!3"-Ym 12#m !-,1'12'Am #,m +320m 2,"1m "#m GFFm 1#+'**1m !-,m "'12',21m !-,!#,20!'-,#1m "#m m m ^FYGZm FYKZmGYFZmGZKm7mHYFmP_m7m- 1#040m*m21m"#m%#0+',!'A,m*m! -m"#m"-1m1#+,1m^'%30m IYH_Ym *m .0'+#0m #$#!2-m "#12! *#m .3"-m - 1#0401#m #,m *1m .*,21m +32"1m m 3,m !-,!#,20!'A,m"#mFYKmPm"#mm7m/3#m3,mHHPm"#m*1m1#+'**1m,-m1#m"#100-**0-,m!-,m ,-0+*'""Ym 12#m 4*-0m 3+#,2 m &12m 3,m KFPm #,m *1m .*,21m 202"1m !-,m "-1'1m m .02'0m"#*mGPm"#mYm-0m*-m2,2-Zm#12#m0#13*2"-m',"'! m/3#m!-,m0,%-1m13.#0'-0#1mm FYKPm"#mm*m%#0+',!'A,m#,m*mFm"'1+',3>m!-,1'"#0 *#+#,2#Ym ,m!3,2-mm*m%#0+',!'A,m"#m*m%#,#0!'A,mHm1#m- 1#04Am3,m.#/3#@m"'1+',3!'A,m #,m*m"-1'1m"#mFYKPZm#,m*m!3*m%#0+',0-,m#*mOIYKGP "#m*1m1#+'**1Zm+'#,201m/3#m#,m*1m "-1'1m *m GPm 7m GYKPm *m "'1+',3!'A,m "#m *m %#0+',!'A,m $3#m *%-m +7-0m - 2#,'#,"-m %#0+',!'-,#1m"#*mNHYMIm7mMKYOJPZm0#1.#!2'4+#,2#Ymm m m m (&30 T DMC[m -0!#,2(#1m "#m %#0+',!'A,m #,m 2,"1m "#m GFFm 1#+'**1m Fm 202"1m !-,m "'12',2-1m .-0!#,2(#1m "#m m ^"#m FPm m HP_Zm "-1m 1#+,1m "#1.3<1m "#*m 202+'#,2-m 1#%B,m *m - 1#04!'A,m "#*m !0#!'+'#,2-m "#m *m %#,#0!'A,m GYm ^Sm 1#+'**1m ,-m %#0+',"1Zm Sm 1A*-m "#100-**-m 0>8Zm Sm !-2'*#"-,#1m ,-0+*#1m 7m "#100-**-m 0>8Zm Sm "#100-**-m ,-0+*_Ym 123"'-m 0#*'8"-m .-0m ,2-,'-m -,$-02#Zm ,m "30"-m 7m -0"'m 0!'m1m"30,2#m#*m@-mHFFJm^_Ym m ',*+#,2#m 1#m "#!'"'Am 310m *1m "-1'1m "#m FZKPZm GPm 7m GZKFPm ^ *m IYH_m .0m +320m *1m 1#+'**1m 7m /3#m <121m .0-"3!>,m 3,-1m ,'4#*#1m !#.2 *#1m "#m 13.#04'4#,!'m #,m *m Gm OG )(-.,/#9(OO/(O*&. ),'OO Resultados ^%#0+',!'A,m13.#0'-0m*mJFPm^'%30mIYH__Zm$#02'*'""m#,m*mGm7m4'%-0m#,m*m%#0+',!'A,m 7m "#100-**-m "#m *m %#,#0!'A,m HYm *m 202+'#,2-m 1#m &'8-m #,m GMYFFFm 1#+'**1Zm .*'!,"-m "'12',21m "-1'1m "#m Ym 1m 1#+'**1m 202"1m 1#m 0#.02'#0-,m #,20#m *-1m "-1m !#,20-1m !-* -0"-0#1m^'#&&-O#.9Zm#,m 0#0m"#m0m^0!#*-,_m7mjm^*#,!'__m .0m 13m !0#!'+'#,2-Ym ,m !"m *3%0m 1#m !0#!'#0-,m *1m .*,21m - 2#,'#,"-m *m %#,#0!'A,m GZm3,/3#m#,m#*m!1-m"#*mm&3 -m3,m"0912'!m.<0"'"m"#m.*,21m"# '"-mm3,m #*#4"m ',!'"#,!'m "#m !-*.1-m "#*m +#*A,m #,m #*m @-m HFFKYm 1m .*,21m Gm 1#m 32-$#!3,"0-,m7m1#m- 234'#0-,mIGJFm$032-1Zm*1m1#+'**1m"#m*1m!3*#1Zm1#m.*,20-,m.0m - 2#,#0m *m %#,#0!'A,m HYm #m !"m 3,-m "#m *-1m $032-1m 1#m .*,20-,m GFm 1#+'**1Zm - 2#,'#,"-m 1>m *m %#,#0!'A,m HYm ',*+#,2#Zm .0m !"m $+'*'m 1#m !-%'Am 3,m "'1!-m "#m &-(m "#m !"m 3,m "#m *1m "'#8m .*9,23*1m HZm /3#m 1#m +#8!*0-,m .0m #620#0m #*m Ym *m ,B+#0-m "#m $+'*'1m Hm #,m *1m /3#m 1#m - 234-m m $3#m HILNYm 12-1m 1m $3#0-,m #,4'"-1m m ,3#120-m * -02-0'-m #,m 0'*1m "-,"#m 1#m 20,1$'0'#0-,m m .*!1m .0m .-12#0'-0+#,2#m-0%,'80m*1m+#8!*1m/3#m$-0+0>,m*m.- *!'A,m"#mYmm T !+ T DMC[m -1'1m "#m m 31"1m .0m +320m *1m 1#+'**1Zm ,B+#0-m "#m .*,21m !-,m $032-1m - 2#,'"-1m #,m *m %#,#0!'A,mGm7m,B+#0-m"#m$+'*'1mHm!-,mm"'1.-,' *#Ym m Dosis EMS Número de frutos recogidos en las plantas M1 Número de familias M2 incluidas en la población de TILLING 0,50% 204 177 1% 2544 1922 1.5% 392 269 TOTAL 3140 2368 m DMBMBMDTTTTTTTTTTTT m .- *!'A,m "#m m#129m 0#.0#1#,2"m #,m Mm .*!1m .--*m ^-m +#8!*_m "-,"#m 1#m &,m +#8!*"-m *-1m 1m "#m *1m HILNm $+'*'1m #,m +#8!*1m "#m !320-m $+'*'1Ym m .- *!'A,m !-,12m "#m 20#1m 2'.-1m "#m .*!1[m 3,1m !-,m *-1m 1m -0'%',*#1m "#m *1m #620!!'-,#1m .0m !"m$+'*'mHm^.*!1me2-!)e_Zm-201m!-,m#*mm"'*3'"-mGiGFm^.*!1me'*32'-,e_mm3,m !-,!#,20!'A,m"#m^Km,%ix*_m7m$',*+#,2#m*1m.*!1m"#m20 (-m/3#m',!*37#,m*m+#8!*m"#m !320-m $+'*'1Ym 1m +#8!*1m 1#m &,m #* -0"-m !-,m 3,m !0'2#0'-m "#m -0"#,m +37m #120'!2-m .3#12-m /3#m .-12#0'-0+#,2#m m *m "#2#!!'A,m "#m *-1m +32,2#1m "# #m .-"#01#m '1*0m #m '"#,2'$'!0m$9!'*+#,2#m*m$+'*'m/3#m!-,2'#,#m*m+32!'A,Ym OH )(-.,/#9(OO/(O*&. ),'OO Resultados *m-0"#,m"#*mm#,m*1m.*!1m!-00#1.-,"#m*m-0"#,m"#m*1m20#1m2,"1m"#m+32!'A,m"#m *1m1#+'**1Ymm,-+#,!*230m31"m.0m*1m$+'*'1mHm*m#12 *#!'#0-,m*-1m"-1m!#,20-1m !-* -0"-0#1m#,m$3,!'A,m"#*m-0"#,m"#m0#!-%'"m"#m*m.*,2m#,m!"m!#,20-Zm1>m2-"1m*1m $+'*'1m/3#m1#m!0#!'#0-,m#,m'#&&-O#.9m^ 0#0m"#m0_m!-+'#,8,m.-0mbcZm+'#,201m /3#m*1m/3#m1#m!0#!'#0-,m#,m#*mjm^*#,!'_m!-+'#,8,m.-0mbcYm1m1#+'**1m "#m2-"1m*1m$+'*'1m#129,m!-00#!2+#,2#m%30""1m7m#2'/3#2"1m#,m#*mjYm *m*'12"-m7m*m.-1'!'A,m.0m!"m$+'*'mHm#,m*1m.*!1m"#m*m.- *!'A,Zm1#m#,!3#,20,m "#2**"-1m#,m#*m,#6-mYYm m DMBMBMETTTTTT$ "-m /3#m #*m +<2-"-m m ,-m & >m 1'"-m 31"-m .0m "#100-**0m .- *!'-,#1m "#m +32,2#1m#,m+#*A,Zm#0m,#!#10'm*m-.2'+'8!'A,m"#m*m2<!,'!m#,m,3#120-m* -02-0'-Ymm 0m .-"#0m "#100-**0m A.2'++#,2#m *m .- *!'A,m "#m +32,2#1m 1#m "#!'"'Am 0#*'80m 3,m #12,!'m #,m #*m %03.-m "#*m 0Ym "#*m #,"&+,#m "#*m jm ^407Zm 0,!'_Ym ,m 3,m .0'+#0m $1#m #,m #*m @-m HFFKm 1#m .0#,"'Am *m 2<!,'!m .0m .-"#0m "#100-**0*m #,m ,3#120-m * -02-0'-Ym m 1#%3,"m $1#m #,m #*m HFFNm 1'04'Am .0m ,*'80m *-1m %#,#1m #,m *1m "'12',21m .- *!'-,#1m "#m +32,2#1m /3#m 1#m & >,m "#100-**"-m #,m #*m * -02-0'-m "#*m Ym #m #1#m +-"-m 1#m .0#2#,">m !-+.00*1m 7m .-"#0m "#2#0+',0m *m #$'!'#,!'m "#m *m .- *!'A,m Em -0m #12#m +-2'4-Zm #,m *-1m .02"-1m 1'%3'#,2#1m 1#m '0,m "#1!0' '#,"-m +32,2#1m!0!2#0'8"-1mm.02'0m"#m*m.- *!'A,m"#*mm7m"#*mYmm m IYGYGYJYGmmmmmm m .- *!'A,m "#m m "#*m m 2'#,#m *%3,1m "'$#0#,!'1m 0#1.#!2-m m *m .- *!'A,m "#*m m 7m /3#m !-,12m "#m 40'1m 13 .- *!'-,#1m - 2#,'"1m .-0m "'12',21m #+.0#11m .0'4"1m "#m 1#+'**1m ^)''Zm m 7m 32'#0_Ym m "'$#0#,!'m "#m *m ,3#120Zm #129m 0#*'8"m !-,m3,m40'#""m2'.-m",(.#-Em*m,B+#0-m"#m$+'*'1m/3#m*m!-+.-,#,m#1m"#mHJNIm7m <121m #129,m +32"1m 31,"-m "-1'1m !-+.0#,"'"1m #,20#m Gm 7m IPm "#m Zm .-0m *-m 2,2-m *m !-,!#,20!'A,m "#m m 1#m 3+#,2Am !-,1'"#0 *#+#,2#m 0#1.#!2-m m *m "-1'1m 31"m #,m *m .- *!'A,mYm"#+91Zm*1m+#8!*1m#129,m!-+.3#121m.-0mNm$+'*'1mHm+'#,201m/3#m *1m ,3#1201m !-,2'#,#,m Jm $+'*'1m Hm ^ *m IYI_Ym + '<,m #1m '+.-02,2#m "#12!0m /3#m .0m+320m*m.- *!'A,m"#*mm1#m310-,m20#1m.0-2-!-*-1m"'12',2-1m#,m*-1m!3*#1m,-m1#m .0#&'"020-,m *1m 1#+'**1m ,2#1m "#m .*'!0m #*m Zm 3,/3#m *-1m .0-2-!-*-1m 1-,m !-,$'"#,!'*#1m7m.#02#,#!#,mm!"m3,m"#m*1m#+.0#11m.0'4"1m/3#m*-1m"#100-**AYm1m '+.-02,2#m 2#,#0m #,m !3#,2m #12#m .3,2-m .3#12-m /3#m .3#"#m ',$*3'0m "#m 3,m +-"-m "#2#0+',,2#m#,m*m#$'!'#,!'m$',*m"#m+32!'A,m"#m*m.- *!'A,Ym OI )(-.,/#9(OO/(O*&. ),'OO Resultados !+ TDMD[m *m!-+.02'4m"#m*1m"-1m.- *!'-,#1m,*'8"1m#,m#12#m20 (-m+#"',2#mYmm m @T % ,(+( 1T CT KTT /+(" "(>-T#$+TT 0($# #T ,(+( 1R,$8"+ T .!+ "(>-T T HILNm FYKZmGZmGYKPm !-,m.0#&'"02!'A,m"#m *1m1#+'**1m '#*m"#m.-m Jm .!+ "(>-T T HJNIm GZmGYKZmHPm 1',m.0#&'"02!'A,m"#m*1m 1#+'**1m &0#,2'1m Nm m IYGYGYJYHmmmmmm -1m .0-2-!-*-1m "#m m 0#!-+'#,",m #*m 31-m "#m +m -*'+#01m !-,m !2'4'""m !-00#!2-0m-m"#m*2m$'"#*'""Ym129m"#1!0'2-m/3#m*m+m2'#,#m3,m21m"#m#00-0m"#mGYG6GFjJm #00-0#1i. m ^0,#1Zm GOOJ_m .-0m #**-m 1#m ','!'0-,m *-1m #6.#0'+#,2-1m !-,m +m .-*'+#011m !-+#0!'*#1m /3#m !-,2#,>,m !2'4'""m !-00#!2-0m !-+-m *m /m ^-!&#_m - 2#,'"m "#m 3,))/-O /,#)-/-Fm!-,m3,m21m"#m#00-0mGYLm6mGFjLm#00-0#1i. m^3," #0%m7m!-*YZmGOOG_m-m*m 2*(m+O*)&3',-m^-!&#_m!-,m3,m21m"#m#00-0m"#mJYNm6mGFjLZm3,/3#m#*m!-12#mm"#m*1m 0#!!'-,#1m #0m #6!#1'4-Ym #m .0- 0-,m *1m +'1+1m +.*'$'!!'-,#1m !-,m +m 1',m !2'4'""m !-00#!2-0m 7m 1#m "#2#0+',Am ^+#"',2#m m 7m 1#!3#,!'!'A,_m 1'm 1#m & >,m @"'"-m #00-0#1m"30,2#m*m+.*'$'!!'A,Zm.3"'#,"-m.0- 0m/3#m,-m#0m1>Ym',*+#,2#Zm1#m"#!'"'Am /3#m 2-"1m *1m +.*'$'!!'-,#1m 1#m &0>,m !-,m +O 1',m !2'4'""m !-00#!2-0Zm 4#0'$'!,"-m .-12#0'-0+#,2#m *m +32!'A,m +#"',2#m 1#!3#,!'!'A,Ym 12#m .3,2-m #1m '+.-02,2#m .3#12-m /3#m0#"3!#m#*m!-12#m"#m*m2<!,'!m!-,1'"#0 *#+#,2#Ym m IYGYGYJYImmmmmO ,m &#00+'#,2m ',"'1.#,1 *#m .0m .-,#0m m .3,2-m #*m m #1m "'1.-,#0m "#m 3,m !-,20-*Ym #m "#!'"'Am 310m 3,m m .0#4'+#,2#m '"#,2'$'!"-m #,m ,3#120-m * -02-0'-Ym ,m HFFLm'#2-m7m!-*Ym'"#,2'$'!0-,m#*m%#,m (-0O^!-00#1.-,"'#,2#m*m%#,m >m"#m+#*A,_m/3#m !-,$'#0#m0#1'12#,!'m*m4'031mm^&)(O,).#O*).O#,/-_Ym*m%#,m(-0m!-"'$'!m.0m 3,m $!2-0m "#m ','!'!'A,m "#m *m 20"3!!'A,m "#m .0-2#>,1m 7m 3,m +32!'A,m #,m #12#m %#,m !-,$'#0#m 0#1'12#,!'m m !'#02-1m 4'031m ^- %*'m 7m 0,2Zm HFFL\m '#2-m 7m !-*YZm HFFK_Ym m +32!'A,m/3#m"m0#1'12#,!'mmm#1m3,m!+ '-m"#m+',-9!'"-m"#m3,m*#3!',m#,m#*m %#,-2'.-m0#1'12#,2#mmGLGIMKm^_mm3,m&'12'"',m#,m#*m%#,-2'.-m131!#.2' *#m^GGG_m#,m*m .-1'!'A,mHHNm"#m*m.0-2#>,Ym12m.-1'!'A,m1#m*-!*'8m#,m#*m#6A,mKZm+91m!-,!0#2+#,2#m#,m *m .-1'!'A,m LNIm "#*m %#,m ^'#2-m 7m !-*YZm HFFL_Ym #!'"'+-1m 310m #12#m m !-+-m !-,20-*m .-1'2'4-m .0m .-,#0m m .3,2-m #*m +<2-"-Ym 0m #**-Zm 1#m 1#!3#,!'Am #*m $0%+#,2-m "#*m %#,m OJ )(-.,/#9(OO/(O*&. ),'OO Resultados >m"-,"#m#129m"#1!0'2m*m+32!'A,m#,m*m*>,#mLHjGGIm7m1#m!-+.0Am!-,m*m1#!3#,!'m "#m *m *>,#1m GGGm 7m Ym m 1#!3#,!'m "#m LHjGGIm 7m GGGm #,m #12m 0#%'A,m #1m '"<,2'!Ym 1>+'1+-m1#m*-!*'80-,m-20-1m.-*'+-0$'1+-1m#,20#mLHjGGIiGGGm7mm^'%30mIYIm_Ymm m T T (&30 T DMD[m _m 1/3#+m "#*m $0%+#,2-m 1#!3#,!'"-m "#*m %#,m >m !-,m *1m .-1'!'-,#1m "#m *-1m .-*'+-0$'1+-1m #,!-,20"-1m#,20#m*1m40'#""#1mLHjGGIm7mYm _m#*m"#mjm3,m4#8m.*'!"-m#*m+<2-"-m"#mmm "'12',21m+3#1201m"#m1Ym"m.,#*m0#.0#1#,2m*-1m!,*#1mMFFm7mNFFZm0#1.#!2'4+#,2#Ymgmm*',#m #,m %0'1m "#2#0+',m #*m 2+@-m m .02'0m "#*m !3*m #*m %#*m .#0">m 0#1-*3!'A,m ^7m .-0m *-m 2,2-m *-1m 2+@-1m "#m *-1m &#2#0-"B.*#6m4'13*'8"-1m#,m#*m%#*m,-m!-',!'"#,m!-,m#*m2+@-m0#*_m!-+-m!-,1#!3#,!'m"#*m3+#,2-m#6!#1'4-m "#m*m2#+.#0230m"#*m%#*m"#m!0'*+'"Ym#m!-+#,209m#,m"#2**#m#,m#*m2#62-Ymm m OK Resultados )(-.,/#9(OO/(O*&. ),'OO m .02#m "#*m m 0#1.-,1 *#m "#m (-0m m NKOiIGFm . m "#m "'12,!'m "#m *-1m !# "-0#1m ;M /&&=Km#,!-,20+-1m3,m',1#0!'A,mm#,m#*m%#,-2'.-mm#,m*m.-1'!'A,mILGiNFNYm *m2#0!#0m.-*'+-0$'1+-m#,!-,20"-m#0m3,mm/3#m#,m#*m%#,-2'.-mLHjGGIm!-,2#,>m3,m m+'#,201m/3#m#,m#*m%#,-2'.-mm!-,2#,>m3,mm#,m*m.-1'!'A,mNONiHMGYm#m+-"-m/3#m*m .*'!0m #*m .0-2-!-*-m "#m m #,m *m +.*'$'!!'A,m "#m #12#m $0%+#,2-m 31,"-m !-+-m m +-*"#m *m +#8!*m "#m + 1m 40'#""#1m - 2#,>+-1m 3,m .20A,m "#m "'%#12'A,m !0!2#0>12'!-m#,m*-1m%#*#1m"#m!0'*+'"m^'%30mIYIm _Ymmm #m310-,m!# "-0#1m7m"'1#@"-1m,2#0'-0+#,2#m.0m+.*'$'!0m*m8-,m"#*mm^'#2-m 7m!-*YZmHFFM_m^(.,)(O;O3O /&&O=K_m7m.-12#0'-0+#,2#m1#m0#*'8Am#*m.0-2-!-*-m40',"-m "'4#01-1m .09+#20-1m .0m .-"#0m "#2#0+',0m *1m !-,"'!'-,#1m A.2'+1m 7m .-"#0m #12,"0'80*1Ym12-1m.09+#20-1m$3#0-,m'_m*m!,2'""m"#mm/3#m"# >+-1m@"'0m#,m *m "'%#12'A,Zm ''_m #*m .-0!#,2(#m "#m "'*3!'A,m "#m *m #,"-,3!*#1Zm '''_m #*m 1'12#+m "#m .30'$'!!'A,m"#m*m0#!!'A,m"#m"'%#12'A,Zm'4_m*m!-,!#,20!'A,m"#m*m+3#120m^#*m2'#+.-m"#m !#,20'$3%!'A,m7m*m2#+.#0230m.*'!"m#,m#*m*_m7m4_m#*m+-"-m"#m!0%m#,m#*mj m ^!-,m .#',#m -m +,3*_Ym ',*+#,2#Zm "#1.3<1m "#m 40'1m .03# 1Zm 1#m #12,"0'80-,m *1m!-,"'!'-,#1m#,m*1m/3#m#*mm!-,20-*m1#m4#>m!-,m+7-0m0#1-*3!'A,Ym#m"#+-120Am/3#m *m .30'$'!!'A,m "#m *m 0#!!'A,m "#m "'%#12'A,m #0m ,#!#10'm .3#12-m /3#m 1'm ,-m 1#m 0#*'8 m .0#!>,m 3,1m ,"1m #,m #*m %#*m "#m jm /3#m ',2#0$#0>,m #,m *m 4'13*'8!'A,m "#m *1m "'%#12'-,#1Ym 1m !-,"'!'-,#1m A.2'+1m "#m !-,!#,20!'A,m "#m *m +3#120m #,m #*m *O $3#0-,m "#m JKm +',32-1m m LKEZm .3#12-m /3#m m +#,-0m 2'#+.-m 7m +#,-0m 2#+.#0230m *m +3#120m /3#" m "#+1'"-m "'*3'"m .0m - 2#,#0m 3,m 4'13*'8!'A,m !-00#!2m #,m #*m j Ym',*+#,2#Zm1#m!-+.0- Am/3#m#*m+<2-"-m"#m!0%m31,"-m*-1m.#',#1m"#1#!& *#1m ^ OL_m.0-.-0!'-, m3,m4'13*'8!'A,m!-,m+#(-0m0#1-*3!'A,m.0m*m'"#,2'$'!!'A,m"#m *-1m!00'*#1m/3#m!-,2'#,#,m+32,2#1m1>m!-+-m*m!.!'""m"#m!0%m^OLm+3#1201m.-0m%#*m +'#,201m/3#m*m!0%m+,3*m1A*-m.#0+'2#m*m!0%m"#mLJm+3#1201_Ym ,m *m '%30mIYIY m.3#"#m4#01#m#*m0#13*2"-m "#m 3,m "#m *1m .03# 1m .0m "#2#0+',0m *-1m .09+#20-1mA.2'+-1m"#*m.0-2-!-*-m7m!-+.0- 0m*m1#,1' '*'""m"#*m+<2-"-Ym,m#*m!,*m MFFm 1#m 4'13*'8m *m "'%#12'A,m "#1"#m #*m !# "-0m "'0#!2-m ^;_m &12m #*m .3,2-m "#m *m "'%#12'A,Zm +'#,201m /3#m #,m #*m !,*m NFFm 1#m 4'13*'8m #*m $0%+#,2-m "#1"#m #*m !# "-0m 0#4#01-m ^ /&&=K_m &12m #*m +'1+-m .3,2-m "#m *m "'%#12'A,m ^'%30m IYI_Ym ,m !-,1#!3#,!'Zm *-1m 2+@-1m "#m *-1m $0%+#,2-1m "'%#0'"-1m /3#m 1#m 4'13*'8,m #,m + -1m !,*#1m "# #,m 13+0m *-m +'1+-m /3#m *m 2-2*'""m "#*m 2+@-m "#*m $0%+#,2-m 1',m "'%#0'0Ym #*m !00'*m Gm *m Nm .3#"#,m 4#01#m *1m "'%#12'-,#1m 0#13*2,2#1m 1#%B,m *-1m "'12',2-1m 1m #+.*#"-1Ym 1m +#8!*1m /3#m !-,2#,%,m 1m !-,m 1#!3#,!'1m "'12',21m +-1200,m *m OL )(-.,/#9(OO/(O*&. ),'OO Resultados "'%#12'A,m .0-"3!'"m .-0m ()O ^!00'*#1m "#*m GjJm 7m L_m +'#,201m /3#m *1m +3#1201m /3#m !-,2#,%,m 1m '%3*#1m #,m 1#!3#,!'m ^M_m -m ,-m 1#,m +#8!*1m "#m 1m ^Km 7m N_m ,-m +-1200,m"'%#12'A,Ym3#"#m- 1#0401#m/3#m#,m!3*/3'#0m"#m*1m"'*3!'-,#1m&#!&1m#,m*1m +#8!*1m"#m*-1m+'1+-1m1m^!00'*#1mGjJ_m*m"'%#12'A,m.-">m"#2#!201#m!-,m*m+'1+m ',2#,1'""Ym-0m*-m2,2-m1#m!-+.0- Am/3#m#,m*1m"'12',21m"'*3!'-,#1m"#mmGiGLZmGiNZm GiJm 7m GiGm ^!00'*#1m GZm HZm Im 7m J_m *-1m &#2#0-"B.*#6m 1#m 4'13*'8 ,m .#0$#!2+#,2#m 7m .09!2'!+#,2#m!-,m*m+'1+m',2#,1'""Ym1m+3#1201m1-,m+#8!*1m"#m"'12',2-1m1m7m "#m "'12',2-1m &#2#0-"B.*#6Ym 1m #,"-,3!*#11m ,-m !-02,m 2-2*+#,2#m 2-"-1m *-1m &#2#0-"B.*#6m 1'+3*29,#+#,2#Ym -0m #12#m +-2'4-m #,m *-1m %#*#1m 1#m .3#"#,m 4'13*'80m *-1m $0%+#,2-1m"#m*-1m"'12',2-1m2+@-1m"#.#,"'#,"-m"#*m&#2#0-"B.*#6m/3#m&7m"'%#0'"-m *m#,"-,3!*#1Ym+ '<,m.-0m#**-Zm#,m*-1m%#*#1m1#m.3#"#,m4'13*'80m#*m2+@-m2-2*m"#*m $0%+#,2-m ,*'8"-m ^.#02#,#!'#,2#m m /3#**1m +3#1201m #,m *1m /3#m ,-m 1#m &m "'%#0'"-m ,',%B,m &#2#0-"B.*#6_m 7m *-1m 2+@-1m "#m !"m &#2#0-"B.*#6m ^.#02#,#!'#,2#1m m /3#**1m +3#1201m#,m*1m/3#m1#m&m"'%#0'"-m!"m3,-m"#m#**-1_Ymm 20m-.2'+'8!'A,m.-12#0'-0m$3#m!+ '0m#*m+-"#*-m"#mjYm*m,3#4-m+-"#*-mJIFFZm ,-1m.#0+'2'Am+#(-01m'+.-02,2#1[m0#"3!'0m#*m2'#+.-m.0m!-00#0m*1m+3#1201Zm3+#,20m *m 0#1-*3!'A,m 7m ,*'80m jMFFm 7m NFFm !-,(3,2+#,2#Zm *-m /3#m .#0+'2#m *m '"#,2'$'!!'A,m .0#!'1m"#m*1m"'%#12'-,#1m7mm*m4#8Zm"#1!020m*-1m02#$!2-1Ym '#,201m /3#m #,m #*m +-"#*-m ,2'%3-m ^'jm H_m #*m 2'#+.-m "#m #*#!20-$-0#1'1m "30 m .0-6'+"+#,2#m 1'#2#m &-01Zm !-,m #*m jm JIFFm !-,1#%3'+-1m 0#"3!'0*-m m IjJm &-01m "#.#,"'#,"-m "#*m $0%+#,2-m m ,*'80Ym "#+91Zm #12-m .#0+'2>m /3#m *-1m %#*#1m 234'#0,m +91m 0#1-*3!'A,m 7m /3#m !-,m Mm &-01m "#m +'%0!'A,m *m !0'*+'"m 3+#,2 m #6!#1'4+#,2#m "#m 2#+.#0230m 7Zm #,m !-,1#!3#,!'Zm *m .02#m 13.#0'-0m "#*m %#*m .#0">m +3!&m0#1-*3!'A,m^'%30mIYI Zm2+@-1m13.#0'-0#1mmJLFm ._Ymm m DMBMCT$ 01m#*m"#100-**-m7m-.2'+'8!'A,m"#m*m.*2$-0+m"#mm#,m+#*A,m! #m"#12!0m /3#m #1m '+.-02,2#m 3,m #123"'-m .0#4'-m "#m +32%<,#1'1m .0m - 2#,#0m 3,m #$'!'#,!'m "#m +32!'A,m"#!3"Ym0m#**-Zm#*m#123"'-m"#*m"#100-**-m"#m*m.*,2m201m*m%#0+',!'A,m 1>m !-+-m #*m "#m *m !.!'""m "#m .0-"3!'0m 1#+'**m Hm 4' *#m #1m +37m '+.-02,2#Ym *m .0-2-!-*-m "#m +32!'A,m "#m *1m 1#+'**1m "# #m 1#0m -.2'+'8"-m .0#4'+#,2#m ,-m 1A*-m .0m $'(0m*m"-1'1m"#m+329%#,-m+91m#$'!'#,2#m1',-m2+ '<,m.0m.*'!0*-m"#m3,m+-"-m#$'!8Ym #%B,m,3#120-1m"2-1m#*m.-0!#,2(#m"#m+329%#,-mA.2'+-m#,m+#*A,m#129m.0- *#+#,2#m "#,20-m"#*m0,%-m"#*mGZKjHZKPYmm OM Resultados )(-.,/#9(OO/(O*&. ),'OO ,m 4#8m "#100-**"m *m .- *!'A,m #1m ,#!#10'm *m .3#12m m .3,2-m "#*m +<2-"-m "#m "#2#!!'A,m 1'#,"-m ',"'1.#,1 *#m 3,m !-,20-*m .-1'2'4-m /3#m .#0+'2m -.2'+'80m 2-"-1m *-1m .1-1m "#*m .0-2-!-*-Zm 1>m !-+-m "'1.-,#0m "#m 3,m 2#!,-*-%>m /3#m .#0+'2m *m "#2#!!'A,m 09.'"m 7m #$'!8Ym ,m #*m !1-m "#m #12#m 20 (-m 1#m "#!'"'Am 310m !-+-m !-,20-*m #*m %#,m >m .3#12-m /3#m 7m 1#m 1 >m /3#m !-,2#,>m 3,m .-*'+-0$'1+-m #,20#m *-1m %#,-2'.-1m "#*m +#*A,m GGGm7m#*m+#*A,m!-0#,-mYm3"'+-1m"#2#0+',0m/3#m,-m.0#!#m,#!#10'-m#*m31-m"#m+m !-,m !2'4'""m !-00#!2-0m 7m /3#m #*m +<2-"-m #1m .0#!'1-m !-,m *m +3#120m "#m m +32,2#m "'*3'"m&12mGLm4#!#1Ym*m+'1+-m2'#+.-Zm"#+-120+-1m/3#m#*m.1-m"#m*m.30'$'!!'A,m"#m *m"'%#12'A,m!-,m()m#1m',"'1.#,1 *#m.0m3,m4'13*'8!'A,mA.2'+m"#m*-1m$0%+#,2-1m #,m*-1m%#*#1m7m/3#m#*mjmJIFFm0',"#m3,m+37m*2m0#1-*3!'A,m7m0#"3!#m#*m2'#+.-m"#m +'%0!'A,m"#m*1m+3#1201Ymm m ON .#9(OO'/.#)(-O Resultados T m DMCT T T T T T T T TTTTTTT m *m +<2-"-m m #129m "'1#@"-m .0m 310*-m %#,#0*+#,2#m !A+-m &#00+'#,2m "#m %#,<2'!m',4#01[m.0'+#0-m1#m#*'%#m3,m%#,m"',m"#*m!3*m/3#0#+-1m#,!-,200m+32,2#1m7m 3,m4#8m#,!-,20"-1m7m#123"'"-1m131m$#,-2'.-1m1#m.3#"#m$-0+3*0m3,m&'.A2#1'1m1- 0#m #*m#$#!2-m-m*m$3,!'-,*'""m"#*m%#,m,*'8"-Ym-1m%#,#1m"',m#,m#12#m20 (-m&,m1'"-m 1#*#!!'-,"-1m 91'!+#,2#m.-0m13m.-1' *#m',2#0<1m%0-,A+'!-Zm#6!#.2-m#,m#*m!1-m"#*m%#,m "#m *m m ^'2-#,-m "#12301_m /3#m $3#m #*#%'"-m !-+-m !-,20-*Ym -1m #$#!2-1m "#m *%3,1m +32!'-,#1m #,m #12#m %#,m &,m 1'"-m "#1!0'2-1m #,m -201m #1.#!'#1m 7m 1#m !0!2#0'8,m .-0m 3,m $3#02#m#$#!2-m.0#+230-m7m/3#m.3#"#m"#2#!201#m4'13*+#,2#Zm#,,'1+-m-m* ','1+-m"#m *m.*,2Zm#1m.-0m#**-m/3#m#12#m%#,m#0m3,m 3#,m!,"'"2-m!-+-m!-,20-*m$#,-2>.'!-m#,m#12#m 20 (-m^',m7m!-*YZmHFFM_Ymm -1m%#,#1m"#m*m$+'*'m"#m*-1m$!2-0#1m"#m','!'!'A,m"#m*m20"3!!'A,m^>m7mI#-)J>_m 1-,m 3#,-1m !,"'"2-1m .0m m .-0m 13m '+.*'!!'A,m #,m 0#1'12#,!'1m m 4'031Zm +91m !-,!0#2+#,2#Zm m .-2'4'031m ^- %*'Zm HFFL\m 3$$#*m 7m !-*YZm HFFJ_Ym ',*+#,2#m #*m ;O ^."3&(O*.),O;_m.3#"#m1#0m3,m%#,m',2#0#1,2#m.-0m13m'+.*'!!'A,m#,m*m0#!#.!'A,m"#m #2'*#,-m 7m #,m !-,1#!3#,!'Zm #,m *m +"30!'A,m "#*m $032-m ^*##Zm GOOO\m '*)',1-,m 7m !-*YZm GOOK_Ym m#1202#%'m1#%3'"m.0m.-"#0m1#!3#,!'0m*-1m%#,#1m1#*#!!'-,"-1m$3#m#,!-,200m1m -m3,'%#,#1m"#m#12-1m%#,#1m#,m 1#1m"#m"2-1m"#m1m"#m+#*A,Ym,m4#8m#,!-,20"m*m 1#!3#,!'m"#m',2#0<1m1#m.0-!#"'Amm"'1#@0m!# "-0#1m.0m.-"#0m+.*'$'!0m7m1#!3#,!'0m .0#$#0' *#+#,2#m *m 0#%'A,m #6A,'!m "#*m %#,m #,m *m *>,#m LHjGGIYm 0m !"m %#,m "'1.-,>+-1m "#m "'$#0#,2#m ',$-0+!'A,Zm 7m /3#m #,m *%3,-1m !1-1m ^!-+-m #,m #*m >_m #*m %#,m 7m #12 m !0!2#0'8"-m 7m #6'12>m 3,m #123"'-m .0#4'-m "#m !-m ^'#2-m 7m !-*YZm HFFM_Ym0m*-1m-20-1m%#,#1m*mB,'!m',$-0+!'A,m"#m*m/3#m1#m"'1.-,>m$3#0-,m1#!3#,!'1m .0!'*#1m "#m 1m ^ *m IYJ_Ym ,m *%3,-1m !1-1m 1#m 1#!3#,!'Am 1A*-m 3,m 0#%'A,m "#*m %#,Zm #1!-%'"m1#%B,m*m',$-0+!'A,m"'1.-,' *#Zm-m201m#*m31-m"#*m.0-%0+mm^))(-O *.#'#4O.)O#-)0,O&.,#)/-O-#)(-_Ymm m T OO .#9(OO'/.#)(-O Resultados !+ T DMEm 2-1m 32'*'8"-1m .0m - 2#,#0m *1m 1#!3#,!'1m "#m *-1m %#,#1m !,"'"2-1Ym ,m *m .0'+#0m !-*3+,m *-1m 3,'%#,#1m 1#*#!!'-,"-1m m .02'0m "#m *m 1#m "#m "2-1m 3Zm #,m *m 1#%3,"m #*m ,B+#0-m "#m !!#1'A,Zm 1'm #129m "'1.-,' *#Zm7m$',*+#,2#Zm#*m!A"'%-m"#m*m,-2!'A,m"#*m%#,m!-00#1.-,"'#,2#m#,mmYmm m $-T T-(&$-T3TT ?,$0.T#$T ""$1(.-TT >#(&.TT HIHGMHm0#%'A,[mOOIKYYGGOGJm I#-)J>O JJOFGmm ^#7#0m7m!-*YZmHFFN_m IFHIFIM m >O ;O O KJLIOm IOINIFm^+m!-+.*#2-_m JNJOOm JMGGJm^,2'%3-m OFMF_m ^'#2-m7m!-*YZmHFFL_m IFFHLONm jm IFFIOFLm jm IFGMMMHm m ,m2<0+',-1m%#,#0*#1m#*m.0-!#"'+'#,2-m#+.*#"-m$3#m/3#Zm3,m4#8m1#!3#,!'"-m2-"-m#*m %#,m -m 3,m $0%+#,2-m "#*m +'1+-Zm 1#m "#100-**0-,m !# "-0#1m #1.#!>$'!-1m .0m *m 8-,m m ,*'80m+#"',2#mm7m1#m,*'8Am!"m%#,m#,m2-"m*m.- *!'A,m"#m+32,2#1m^Mm .*!1m "#m +#8!*_Ym ,m 4#8m "#2#!2"-1m *-1m +32,2#1m 1#m &'!'#0-,m *1m "#!-,4-*3!'-,#1m !-00#1.-,"'#,2#1m ^'"#,2'$'!!'A,m "#m *m $+'*'m 0#1.-,1 *#m "#m *m +32!'A,m "#,20-m "#m *m +#8!*_Ym -12#0'-0+#,2#Zm 1#m 1#!3#,!'0-,m 7m ,*'80-,m *1m +32!'-,#1m "#2#0+',,"-m 1'm <121m#12 ,m#,m3,m0#%'A,m',20A,'!m-m#6A,'!Ym1m*-!*'8"1m#,m3,m0#%'A,m#6A,'!m 1#m#123"'0-,m!-,m+91m"#2**#m'"#,2'$'!,"-m!A+-m$#!2 mm*m.0-2#>,m7m1'm*m+32!'A,m .0-4-! m 3,m !+ '-m "#m +',-9!'"-Ym ,m /3#**-1m !1-1m #,m /3#m #*m !+ '-m #0m 1'%,'$'!2'4-m ^1#%B,m 4*-0m "#m .0-%0+m ',$-0+92'!-m _m 1#m 1-*'!'2Am *m 1#+'**m "#m *m $+'*'m +32"m 7m 1#m - 1#04Am #*m $#,-2'.-Ym #m #620(-m #*m m "#m *-1m ',"'4'"3-1m .0m !-+.0- 0m*m1#%0#%!'A,m"#m*m+32!'A,m#,m*m$+'*'Zm3,/3#m#12#mB*2'+-m.1-m1A*-m1#m 0#*'8Am#,m#*m%#,mYmm T DMCMBTTPTQT 0m#+.#80mm310m*m.- *!'A,m"#mm1#m"#!'"'Am1#*#!!'-,0m3,m%#,m!-,20-*m!-,m #*m /3#m O*,#),#O$3#0m +91m 1#,!'**-m ,*'80m #*m $#,-2'.-m "#m *-1m +32,2#1Ym *m %#,m #1!-%'"-m $3#m #*m "#m *m m ^'2-#,-m "#12301_m /3#m #129m ',4-*3!0"-m #,m *m 032m "#m 1>,2#1'1m "#m !0-2#,-1Ym ',m 7m !-* -0"-0#1m "#+-1200-,m /3#m *m "'103.!'A,m "#m #12#m %#,m #,m ,#)*-#-O .0-4-!m $#,-2'.-1m * ',-1m 7m #,,-1m !-+-m !-,1#!3#,!'m "#*m #$#!2-m "#m ',2#003.!'A,m #,m *m '-1>,2#1'1m "#m !*-0-$'*Zm !0-2#,-'"#1m 7m %' #0'*',1m ^',m 7m !-*YZm HFFM_Ym 1>m .3#1Zm 1'm "#2#!29 +-1m 3,m $+'*'m +32,2#m #,m *m %#,#0!'A,m Hm #,m *m /3#m *m +32!'A,m '+.*'!0m 3,m !+ '-m "#m +',-9!'"-Zm #1.#09 +-1m - 1#040m *%3,-1m "#m *-1m GFFm .#9(OO'/.#)(-O Resultados $#,-2'.-1m "#1!0'2-1m ,2#0'-0+#,2#m #,m -201m #1.#!'#1Ym 12-m "#+-1200>m /3#m *m .- *!'A,m !-,2'#,#m +32,2#1Zm /3#m #*m +<2-"-m "#m "#2#!!'A,m #1m !-00#!2-m 7m /3#m "#+91Zm .3#"#,m - 2#,#01#m+32,2#1m!-,m$#,-2'.-m1-!'"-Ym '+3*29,#+#,2#mm#12#m20 (-m1#m"#100-**Am3,m 1#m"#m"2-1m"#m1m"#m+#*A,m#,m#*m +0!-m "#*m .0-7#!2-m 3m ^555Y'!3%'Y-0%_Ym #m #12#m +-"-m 234'+-1m m ,3#120-m *!,!#m 3,m&#00+'#,2m#$'!'#,2#m.0m 31!0m1m"#m3,m%#,m"#2#0+',"-m7m.-"#0m.0-!#"#0m*m "'1#@-m"#m!# "-0#1m/3#m,-1m1'04'#0,m.0m- 2#,#0m*m1#!3#,!'m!-+.*#2m"#*m%#,m#,m*m *>,#m LHjGGIYm 0m *m m #,!-,20+-1m 3,m B,'!-m m ^OFMF_Zm !23*+#,2#m "#,-+',"-mJMGGJYm m DMCMBMBTTTTTT$T 02'#,"-m"#*mmOFMFm/3#m!-,2#,>m3,m*2m&-+-*-%>m^OIP_m!-,m#*m%#,m"#m*mm "#m )'),#O",(.#m INLGFKYG_Zm "'1#@+-1m "-!#m !# "-0#1m !-+ ',9,"-*-1m #,20#m 1'm ^'%30m IYJ_m .0m .-"#0m - 2#,#0m *m 1#!3#,!'m %#,A+'!m #,m *m *>,#m LHjGGIm /3#m ',!*37#0m *1m 0#%'-,#1m ',20A,'!1Ym ',*+#,2#m +.*'$'!+-1m 7m 1#!3#,!'+-1m 3,m 0#%'A,m %#,A+'!m"#mJKIMm. Ym *m ,-m "'1.-,#0m "#m *m 1#!3#,!'m !-+.*#2m "#*m %#,m "#m *m m #,m +#*A,m 31!+-1m -02A*-%-1m#,m#1.#!'#1m!#0!,1Ym3"'+-1m'"#,2'$'!0m/3#m"'!&m1#!3#,!'m!-00#1.-,">mm *-1mB*2'+-1mLm#6-,#1m"#m*mm"#m)'),#O",(.#OINLGFKYG_m^0#%'A,m+0!"m#,m %0'1m#,m*m'%30mIYK_Ym',m#+ 0%-Zm,-m1#m1'%3'Am!-,m*m1#!3#,!'!'A,m"#*m%#,m!-+.*#2-m ""-m /3#m #,m #1#m +-+#,2-m ,-m 1#m "'1.-,>m "#m +91m 1m 7m "#+91Zm 1#m !-,1'"#0Am /3#m #*m $0%+#,2-m1#!3#,!'"-m 12 m.0m','!'0m*m B1/3#"m"#m+32,2#1m""-m/3#m!-,2#,>m .0-6'+"+#,2#m *m +'2"m "#m 0#%'A,m #6A,'!m ^#6-,#1m "#*m Om *m GJ_Ym !23*+#,2#Zm 1#m "'1.-,#m"#m*m1#!3#,!'m!-+.*#2m"#*m%#,-+m"#*m+#*A,Zm&#00+'#,2m/3#m&m.#0+'2'"-m '"#,2'$'!0m#*m%#,m!-+.*#2-m"#m*mYm,m*m'%30mIYKm1#m.3#"#m- 1#040m*m#1203!230m "#*m%#,Zm/3#m!-,2'#,#mGJm#6-,#1Ymm m m GFGm .#9(OO'/.#)(-O Resultados m (&30 TDME[m1/3#+m0#.0#1#,22'4-m"#m*m0#%'A,m"#mm"#m+#*A,m#,20#m*-1m#6-,#1mOm7mGJYm_m,m+-0"-Zm*-1m !# "-0#1m32'*'8"-1m.0m*m1#!3#,!'!'A,m"#*m%#,mm^,#6-m_m _m1/3#+m"#m*m1#!3#,!'m"#m0#$#0#,!'m "#m*m!3*m1#m.02'Am.0m#*m"'1#@-m"#m!# "-0#1m7m/3#m!-00#1.-,"#m*mmOFMFm#620>"m"#m*m 1#m"#m"2-1m "#*m3Ym!_m#!3#,!'m- 2#,'"m"#1.3<1m"#m*m+.*'$'!!'A,m7m1#!3#,!'!'A,m!-,m*-1m!# "-0#1m',"'!"-1Ym"_m +.*'!A,m#1!-%'"-m.0m#*m,9*'1'1m+#"',2#mYmm m #m &m .-"'"-m 0#*'80m 3,m *',#+'#,2-m +B*2'.*#m !-,m #*m %#,m "#m *m m '"#,2'$'!"-m #,m +#*A,m ^IFGMMMH_m 7m -201m #1.#!'#1m !-,m 2*m "#m - 1#040m *1m 0#%'-,#1m +91m !-,1#04"1m7m.-12#0'-0+#,2#m,*'80m*m.-1'!'A,m"#m*1m+32!'-,#1m"#2#!2"1m^'%30m IYK_Ym "#+91Zm 7m %0!'1m m &#00+'#,21m /3#m !23*+#,2#m #12,m "'1.-,' *#1m #,m +#*A,m !-+-m#*m'*-+m^.&7*-+#" Y-0%_Zm1#m&m- 2#,'"-m#*m90 -*m$'*-%#,<2'!-m"#*m%#,m.3"'#,"-m !-00- -00m /3#m *m 1#!3#,!'m "#m *m /3#m "'1.-,>+-1m !-00#1.-,"#m *m %#,m "#m *m m ^'%30m IYLZm $*#!&m 0-(_m 7m /3#m #*m 90 -*m $'*-%#,<2'!-m *-m 0#*!'-,m !-,m 13m -02A*-%-m "#m ,#)*-#-O^'%30mIYLZm$*#!&m83*_Zm/3#m#129m!-00#!2+#,2#m,-2"-Em*m+'1+-m2'#+.-Zm #12m&#00+'#,2m,-1m.#0+'2#m$'0+0m/3#m&7m3,m1-*m!-.'m"#m#12#m%#,m#,m#*m%#,-+m "#*m+#*A,m^'%30mIYL_Ym,m#*m+'1+-m90 -*m$'*-%#,<2'!-m.0#!#,m2+ '<,m"-1m%#,#1m"#m*m #2j!0-2#,-m "#12301m ^_m ^&7FFIIfm 7m &7FFIGf_Zm !#0!,m$'*-%#,<2'!+#,2#mmYm ,m4#8m- 2#,'"m#12m0#%'A,m"#m*m1#!3#,!'m"#*m%#,m#1!-%'+-1m#*m$0%+#,2-mm,*'80m +#"',2#m Ym 0m #*#%'0*-m "# >m 2#,#01#m #,m !3#,2m /3#m #*m 2+@-m A.2'+-m "#m 0#1-*3!'A,m "#m *-1m $0%+#,2-1m #,m #*m jm JIFFm #1m "#m GFFFm . m .0-6'+"+#,2#Ym -0m #12#m+-2'4-Zm*-1m+.*'!-,#1m,*'8"-1m#,m#12#m20 (-m,-m1- 0#.1,m*-1mGHFFm. Ym0m ,*'80m%#,#1m"#m2+@-m+7-0m"#mGm &!#m$*2m"'1#@0m40'-1m+.*'!-,#1 m.02'0m "#m"'12',21m.02#1m"#*m%#,Ymm m GFHm m .#9(OO'/.#)(-O Resultados m m m (&30 T DMFm #!3#,!'m .0-2#'!m "#*m %#,m "#m *m m #,m +#*A,m /3#m !-,2'#,#m GJm #6-,#1Ym *m %#,m IFGMMMHm ^OMFOm. _m&m1'"-m,-2"-mm.02'0m"#* %#,-+m"#*m+#*A,Y #m+3#120m#*m*',#+'#,2-m+B*2'.*#m!-,m)'),#O ",(.#Zm ,!,#O ((-m 7m O '3-m 7m *m .-1'!'A,m "#m *1m +32!'-,#1m '"#,2'$'!"1m #,m #12#m %#,m +#"',2#m m#,m#*m.0#1#,2#m20 (-m^83*m7m4#0"#_Ym,m%0'1m*m8-,m0#.0#1#,2"m.-0m#*m3,'%#,mOFMFm-0'%',*Ym T GFIm Resultados .#9(OO'/.#)(-O (&30 T DMG[m 0 -*m $'*-%#,<2'!-m "#*m %#,m "#m *m m "#m +#*A,m ^&7FFIOm -m IFGMMMH_m 7m "#m -201m HIm #1.#!'#1m 4#%#2*#1Ym m *m "#0#!&m #*m "#2**#m "#m *m .-1'!'A,m "#m *m m "#m +#*A,m ^$*#!&m 0-(_m 1>m !-+-m "#m 13m -02A*-%-m#,m,#)*-#-m^$*#!&m83*_m#,m#*m90 -*m$'*-%#,<2'!-m^$3#,2#[m&7*-+#" Y-0%_Ym m *m+'1+-m2'#+.-Zm#*m.0-%0+m (.'#2&m7m51-,ZmHFFK_m,-1m',"'!m*m0#%'A,m !-,m+91m.0- '*'""m"#m13$0'0m3,m!+ '-m"#m+',-9!'"-m201m*m+32%<,#1'1m7m/3#m#12#m !+ '-m1#m1'%,'$'!2'4-m.0m*m$3,!'-,*'""m"#m*m.0-2#>,Ym#,'#,"-m#,m!3#,2m#12-1m "2-1m1#m#*'%'Am#*m$0%+#,2-m"#2**"-m#,m*m'%30mIYJm"_m!-,m3,m2+@-m2-2*m"#mGGNOm. m 7m/3#m',!*37#m.09!2'!+#,2#m*-1m20#1mB*2'+-1m#6-,#1Ym ,m*-1m.0'+#0-1m%#*#1m0#*'8"-1m!-,m*mm1#m',!*37AZmm.02#m"#*m!-,20-*m.-1'2'4-m/3#m 1#m& >m32'*'8"-m&12m#1#m+-+#,2-m^>N(-0_m^.02"-mIYGYGYJYI_Zm3,m+3#120m/3#m !-,2#,>m *m +#8!*m "#m *-1m +.*'!-,#1m m m .02'0m "#m *1m 40'#""#1m GGGm 7m Ym *m GFJm T .#9(OO'/.#)(-O Resultados .*'!0m #*m .0-2-!-*-m "#m m #,m #12m +3#120m - 1#04+-1m /3#m .0#!>,m 40'-1m &#2#0-"B.*#6m^'%30mIYM_Ym#!'"'+-1m'"#,2'$'!0m*-1m1m#,20#mGGGm7mZm#,!-,20,"-m ,3#4#m .-*'+-0$'1+-1Ym #!'"'+-1m 310m #12#m $0%+#,2-m !-+-m ,3#4-m !-,20-*m .-1'2'4-m #,m *-1m %#*#1m "#m Zm .3#12-m /3#m !-,2#,>m +91m 1m 7m *m 0#1-*3!'A,m #0m +#(-0m /3#m *m - 2#,'"m.0m#*m$0%+#,2-m"#*m%#,m>m!-+#,2"-m,2#0'-0+#,2#Ymm m m (&30 TDMHm1/3#+m"#*m$0%+#,2-m"#m*mm,*'8"-m+#"',2#mYmm+ -1m*"-1m"#m*m$'%30m#129,m *1m "'%#12'-,#1m #,m *-1m "-1m !,*#1m "#*m jm ^"#0#!&Zm NFFZm !-*-0m 4#0"#\m '8/3'#0"Zm MFFZm !-*-0m 0-(-_m +'#,201m /3#m #,m *m .02#m !#,20*m .3#"#m 4#01#m 3,m 0#.0#1#,2!'A,m "#*m $0%+#,2-m ,*'8"-m 7m *m .-1'!'A,m ^.02'#,"-m "#m !"m 3,-m "#m *-1m "-1m !# "-0#1m 32'*'8"-1m ^"'0#!2-[m Jm 7m 0#4#01-m __m "#m *-1m 1m "#2#!2"-1m+#"',2#m1#!3#,!'!'A,m#,20#mGGGm7mYm,m*mB*2'+m 00m1#m"#2**,m*1m"'12,!'1m#,20#m1Ym m DMCMBMCTNTTTTTTTT 01m 0120#0m HILNm $+'*'1m Hm "#m *m .- *!'A,m m 7m HJNIm "#m *m .- *!'A,m m 1#m "#2#!20-,m "-1m ^GGKGm 7m INJ_m 7m !320-m ^GGNHZm HJOKZm GHHLm 7m GJLF_m +32,2#1m 0#1.#!2'4+#,2#m ^'%30m IYOZm *m IYK_m .0m #*m %#,m Ym "m $+'*'m +32,2#m 1#m GFKm .#9(OO'/.#)(-O Resultados '"#,2'$'!Am +#"',2#m "#!-,4-*3!'A,m 7m .-12#0'-0+#,2#m 1#m "#2#!2Am 7m !-+.0- Am #*m m +#"',2#m 1#!3#,!'!'A,m 7m ,9*'1'1m "#m *-1m !0-+2-%0+1Ym ,m 2-"-1m *-1m +32,2#1m 1#m '"#,2'$'!Am *m +32!'A,m #,m #*m !0-+2-%0+m !-+-m 3,m "- *#m .'!-m "#*m ,3!*#A2'"-m #,m *m .-1'!'A,m "#m *m +32!'A,Zm "# '"-m m /3#m #*m $0%+#,2-m ,*'8"-m 1#m & >m +.*'$'!"-m m .02'0m "#m 3,m +#8!*m "#m m "#m "'#8m ',"'4'"3-1m "#m !"m $+'*'m HYm #"',2#m #*m #123"'-m "#*m !0-+2-%0+m ^'%30m IYN_m 1#m "#2#0+',Am *m .-1'!'A,m "#m *m +32!'A,m 7m 1#m '"#,2'$'!Am#*m!+ '-m"#m,3!*#A2'"-Ym m m m (&30 TDMI[m 0-+2-%0+1m "#m *1m "-1m $+'*'1m !-,m +32!'-,#1m #,m *m 8-,m #6A,'!m "#m *mm ^INJm 7m GGNH_Ym -1m !0-+2-%0+1m "#m *m .02#m 13.#0'-0m !-00#1.-,"#,m m *-1m %#,-2'.-1m &-+-!'%-2-1m 1'*4#120#1m ^1i1_m "#m LHj GGIZm+'#,201m/3#m*-1m!0-+2-%0+1m"#m*m.02#m',$#0'-0m!-00#1.-,"#,mm*-1m%#,-2'.-1m&#2#0-!'%-2-1m+32,2#1m ^+i1_Ym,m#12-1mB*2'+-1m1#m.3#"#m- 1#040m#*m"- *#m.'!-m/3#m0#.0#1#,2m*m&#2#0-!'%-1'1m"#*m*#*-m^.3#12-m/3#m#*m m.)%m"#m!"m$+'*'m#129m!-+.3#12-m.-0m3,m+#8!*m"#mGFm',"'4'"3-1_Ymm m ,m *m '%30m IYOm .-"#+-1m - 1#040m *m 0#.0#1#,2!'A,m "#*m %#,m "#m *m m ',"'!,"-m #*m $0%+#,2-m ,*'8"-m +#"',2#m m 7m *1m .-1'!'-,#1 "A,"#m 1#m &,m "#2#!2"-m *1m +32!'-,#1m #,m *1m $+'*'1m "#m !"m .- *!'A,m ^Zm 20'9,%3*-1m #,m 0-(-m 7m m 20'9,%3*-1m#,m4#0"#_Ym,m*m *mIYKm1#m"#1!0' #,m!-,m+91m"#2**#m*1m!0!2#0>12'!1m"#m !"m+32!'A,Ym+ '<,Zm#*m.-0!#,2(#m"#mm*m/3#m#12 m+32%#,'8"m*m1#+'**m7m #*m !+ '-m "#m +',-9!'"-m /3#m .0-4-!m *m +32!'A,Ym -1m "#m *-1m +32,2#1m #,!-,20"-1m ^GGNHm7mINJ_m.0#1#,2,m*m+32!'A,m#,m0#%'A,m#6A,'!Zm!-,!0#2+#,2#m#,m*-1m#6-,#1mGHm 7m GIm "#*m %#,Zm 0#1.#!2'4+#,2#Ym -1m !320-m +32,2#1m 0#12,2#1m ^GHHLZm GJLFZm HJOKZm GGKG_m .0#1#,2,m*1m+32!'-,#1m#,m#*m',20A,mGHYm-"-1m*-1m!+ '-1m$3#0-,m"#m!'2-1',mm2'+',Zm &#!&-m /3#m !-,$'0+m #*m #$#!2-m "#*m m ^20,1'!'-,#1m jij_m ^#,')-$$m 7m -+'Zm HFFI _Ym m GFLm .#9(OO'/.#)(-O Resultados m m (&30 TDMJ[m#.0#1#,2!'A,m"#m*m.02#m1#!3#,!'"m"#m*mm^'2-#,-m"#12301_m"A,"#m*1m!(1m0#.0#1#,2,m *-1m#6-,#1m7m*m.02#m*',#*m*-1m',20-,#1Ym,m*m.02#m13.#0'-0Zm1#m"#2**m*m0#%'A,m"#*m%#,m"#mGGNNm. m,*'8"-m +#"',2#m m 7m #,m *m .02#m ',$#0'-0m *m .-1'!'A,m "#m *-1m +32,2#1Ym -1m 20'9,%3*-1m 0-(-1m 0#.0#1#,2,m *-1m +32,2#1m #,!-,20"-1m #,m *m .- *!'A,m "#*m m +'#,201m /3#m *-1m 4#0"#1m 0#.0#1#,2,m *-1m #,!-,20"-1m #,m *m .- *!'A,m"#*mm^#12m!-"'$'!!'A,m"#m!-*-0m1#m+-12009mm*-m*0%-m"#*m20 (-_Ym m !+ TDMF[m32,2#1m#,!-,20"-1m#,m#*m$0%+#,2-m"#mGGNNm. m"#*m%#,mO,*'8"-Ym,m$-,"-m0-(-m/3#**-1m +32,2#1m #,!-,20"-1m #,m *m .- *!'A,m m 7m #,m $-,"-m 4#0"#m /3#**-1m #,!-,20"-1m #,m *m .- *!'A,m Ym g-1'!'-,#1m0#1.#!2-m*m!# "-0m"'0#!2-mJYm T Nº Familia Posición Mutación* Cambio aa 1 2 3 %EMS SIFT 1182 Exón 12 C395T Ser485Phe 2495 Intrón 12 C/T 2% 2% 0.01 1226 Intrón 12 C/T 2% 4 1460 Intrón 12 C/T 2% 5 F1151 Intrón 12 C/T 1% 6 C384 Exón 13 C560T Ser540Phe 1% 0.00 1m $+'*'1m INJm 7m GGNHm !-,2'#,#,m 3,m +32!'A,m #,m 0#%'A,m #6A,'!m /3#m .0-4-!m #*m +'1+-m !+ '-m "#m +',-9!'"-m "#m 1#0',m m $#,'**,',m ^7m /3#m + 1m !+ ',m "#*m !-"A,mmm_Zm*m.0'+#0m#,m*m.-1'!'A,mJNKm7m*m1#%3,"m#,m*m.-1'!'A,mKJFm"#m*m 1#!3#,!'m.0-2#'!m"#*m%#,m"#m*mm^IFGMMMH_m^'%30mIYKZm.-1'!'-,#1m+0!"1m #,m83*m7m4#0"#_Y m .0#"'!!'A,m "#m !A+-m #12#m !+ '-m "#m +',-9!'"-m .3#"#m $#!20m m *m .0-2#>,m .3#"#m !-+.0- 01#m+#"',2#m#*m,9*'1'1m!-,m#*m.0-%0+mm^),.#(!O(.)&,(.O,)'O)&,(.Zm &22.[ii *-!)1Y$&!0!Y-0%i1'$2iY&2*+_m ^3*',#m 7m #,')-$$Zm HFFI_Ym ,20-"3!'#,"-m #,m #*m m*m1#!3#,!'m.0-2#'!m-m*m"#*m%#,m#m',"'!,"-m*m1312'23!'A,m+',-!>"'!Zm&!#m3,m .0-6'+!'A,m +2#+92'!m +#"',2#m !-+.0!'A,m !-,m 1#!3#,!'1m -02A*-%1m 7m "m 3,m .3,23!'A,m"#m!A+-m#12#m!+ '-m.3#"#m$#!20mm*m$3,!'-,*'""m"#m*m.0-2#>,Ym#%B,m m*1m13 12'23!'-,#1m!-,m3,m.3,23!'A,m+#,-0m"#mFYFKm$#!209,mm*m$3,!'-,*'""m GFMm Resultados .#9(OO'/.#)(-O "#m*m.0-2#>,m+'#,201m/3#m3,m.3,23!'A,m+7-0m',"'!m/3#m.0- *#+#,2#m#*m!+ '-m ,-m $#!2m m *m $3,!'A,m "#m *m .0-2#>,Ym ,m 2-"-1m *-1m +32,2#1m "#m 2-"-1m *-1m %#,#1m ,*'8"-1m #,m #12#m 20 (-m 1#m &m &#!&-m #12#m ,9*'1'1Ym 0m *m Zm #,m + -1m !1-1m m .0#"'!#m /3#m *m +32!'A,m .3#"#m !310m 3,m #$#!2-m #,m *m $3,!'A,m "#m *m .0-2#>,m !-,1'"#09,"-*m ,-m 2-*#0"Ym #,'#,"-m #,m !3#,2m /3#m *m 1#0',m #1m 3,m +',-9!'"-m .-*0m ,-m !0%"-m 7m *m $#,'**,',m #1m 3,m +',-9!'"-m ,-m .-*0m ^'%30m IYGF_Zm "#+91m "#*m 0#13*2"-m "#m *m .0#"'!!'A,m "#m Zm "#!'"'+-1m 1#%3'0m !-,m *m - 1#04!'A,m $#,-2>.'!m "#m #12-1m+32,2#1Ymm m m (&30 TDMBA[m#.0#1#,2!'A,m"#m*-1mHFm+',-9!'"-1Ym#.#,"'#,"-m"#*m%03.-m0"'!*m<12-1m.3#"#,m!*1'$'!01#m #,m .-*0#1Zm .-*0#1m ,-m !0%"-1m 7m "#,20-m "#m *-1m .-*0#1m !0%"-1m #,20#m 9!'"-1m 7m 91'!-1Ym ,m #*m !1-m "#m *1m $+'*'1m +32,2#1m INJm 7m GGNHm #*m !+ '-m "#m 1#0',m m $#,'**,',m .3#"#m +-"'$'!0m *1m .0-.'#""#1m "#m *m #1203!230m.3#12-m/3#m1#m.0-"3!#m3,m1312'23!'A,m"#m3,m+',-9!'"-m1',m!0%mm3,-m.-*0m.#0-m!-,m3,m%03.-m 0"'!*m+3!&-m+91m%0,"#Ym T DMCMBMDTTTTTTTTDIETTBBBFT -1m.0'+#0-1m+32,2#1m"#2#!2"-1m#,m#*mm+#"',2#mm$3#0-,m*-1m"#*m%#,m"#m *mYm#m!-,2',3Am#*m,9*'1'1m"#m#121m$+'*'1m.-0/3#m"'1.-,>+-1m"#m*1m1#+'**1m"#m *1m$+'*'1mHm.0m.-"#0m,*'80m#*m$#,-2'.-Ym,m!+ '-Zm,-m1#m!-,2',3Am#*m,9*'1'1m"#m *m$+'*'mGGNHm.3#12-m/3#m#12#m+32,2#m1#m"#2#!2Am.-12#0'-0+#,2#m#,m#*mm7m,-m&3 -m 2'#+.-m +2#0'*m "#m 1-*'!'20m *1m 1#+'**1m Hm 7m $#,-2'.0*1Ym 0m *m $+'*'m INJm #0m GFNm .#9(OO'/.#)(-O Resultados $!2' *#m 4'13*'80m *%B,m $#,-2'.-m .3#12-m /3#m *m +32!'A,m #12 m #,m 0#%'A,m #6A,'!m 7m .0-"3!>m3,m!+ '-m"#m+',-9!'"-m^ *mIYK_Ym-0m#*m!-,200'-Zm.0m*m$+'*'mGGKGZm 2+ '<,m"#m*m.- *!'A,m"#*mZm,-m1#m#1.#0 m,',%B,m#$#!2-m$#,-2>.'!-m.3#12-m/3#m*m +32!'A,m 1#m #,!3#,20m #,m 0#%'A,m ',20A,'!Ym ',m #+ 0%-Zm 2+ '<,m 1#m 0#*'8Am #*m #123"'-m "#m*m1#%0#%!'A,m"#m*m+32!'A,m.0m#12m$+'*'Ym*m.-0!#,2(#m"#m%#0+',!'A,m"#m*1m 1#+'**1mHm$3#m#*#4"-Zm#,m*m$+'*'mINJm$3#m"#*mNFPm+'#,201m/3#m#,m*m$+'*'mGGKGm $3#m"#*mNNPm^ *mIYL_Ymm m !+ TDMG[m#0+',!'A,m"#m*m1#+'**1mHm#,m*1m$+'*'1mINJm7mGGGKYm m +'*'m #+'**1m .*,2"1m #0+',"1m *,21m"3*21m *,21m!-,m$032-m INJm HFm GLm GJm Nm GGKGm HKm HHm HHm HFm m 0m*m$+'*'mGGKGm1#m201.*,20-,m*m',4#0,"#0-m*1mHHm.*,21m%#0+',"1m7m,-m1#m - 1#04Am,',%B,m$#,-2'.-Ym,m#12m$+'*'m#*m.-0!#,2(#m"#m<6'2-m"#m!3("-m"#m*-1m$032-1m $3#m #*#4"-m ^OFZOP_m ^ *m IYL_Ym -1m $032-1m "#m + 1m $+'*'1m $3#0-,m +#"'"-1Zm $-2-%0$'"-1m 7m ,*'8"-1m $#,-2>.'!+#,2#m .#0-m ,-m 1#m - 1#04Am ,',%3,m 40'!'A,m '+.-02,2#m 0#1.#!2-m *m !-,20-*m ^'%30m IYGG_Ym 1m 1#+'**1m Im "#m #12-1m $032-1m 1#m 0#!-%'#0-,m7m*+!#,0-,Ym m m m (&30 TDMBB[m+%#,m"#m20#1m$032-1m"#m.*,21mHm0#!-%'"-1m"#m*1m$+'*'1mINJm^'8/3'#0"_ZmGGGKm^"#0#!&_Zm7m !-,20-*mLHjGGIm^!#,20-_Ym m GFOm Resultados .#9(OO'/.#)(-O #m *m $+'*'m GGKGm 1#!3#,!'+-1m GKm ',"'4'"3-1m "#m *-1m !3*#1m #,!-,20+-1m Jm &-+-!'%-2-1m 1'*4#120#1Zm Mm &#2#0-!'%-2-1m 7m Jm &-+-!'%-2-1m +32,2#1Zm "#m +-"-m /3#m 1#m !3+.*>m*m1#%0#%!'A,m#1.#0"mG[H[Gm^ *mIYM_Ymm ,m *m $+'*'m INJm .3"-m 4#01#m 3,m $#,-2'.-m !0!2#0>12'!-m /3#m !-,1'12#m #,m 3,m 3*2+'#,2-m -m +*$-0+!'A,m "#m *m &-(m 1>m !-+-m 3,m !0#!'+'#,2-m 0*#,2'8"-m "#m *m .*,2Ym 12#m $#,-2'.-m 1#m "#2#!2Am #,m Km .*9,23*1m 3,/3#m ,-m #,m 2-"1m #**1m !-,m *m +'1+m ',2#,1'""m^*#!&1m83*#1m#,m'%30mIYGH_Ym ,m 3,m #12"'-m +91m "#*,2"-m "#m .*9,23*m ^"-1m 1#+,1m 201m *m %#0+',!'A,_m .3"-m - 1#0401#m #12#m $#,-2'.-m "#m 3,m +-"-m +91m !#,23"-m #,m Lm "#m *1m GLm .*9,23*1m %#0+',"1Ym -1m !-2'*#"-,#1m #12 ,m +37m 003%"-1m 7m 1#m 1#! ,Ym 1m .0'+#01m &-(1m "#m #121m .*9,23*1m +-120 ,m 3,m 0#201-m "#m !0#!'+'#,2-m #,m !-+.0!'A,m m *1m /3#m ,-m .0#1#,2 ,m #12#m $#,-2'.-m 7m #,m *%3,1m "#m #**1m ,-m & >m ,'m 1'/3'#0m .0#1#,!'m "#m *1m .0'+#01m&-(1Ym#m#121m.*,21m+30'Am3,m"#m*m!3*m,-m.3"'+-1m0#!-%#0m+3#120Ym*m ! -m"#mJm1#+,1m.0-6'+"+#,2#Zm*1m.*,21m1#m.10-,m*m',4#0,"#0-m.0m.-"#0m 1#%3'0m #*m #123"'-m $#,-2>.'!-m #,m *m .*,2m "3*2Ym ,m .*,2m "3*2Zm ,-m 1#m - 1#040-,m !0!2#0>12'!1m $#,-2>.'!1m "'$#0#,!'*#1m "#m *1m .*,21m !-,20-*Zm .#0-m 3,m 4#8m 32-.-*','8"1Zm 7m 2#,'#,"-m #,m !3#,2m /3#m !0#!>+-1m 3,m $032-m .-0m .*,2Zm 1A*-m 1#m - 234'#0-,mNm$032-1m"#mGJm.*,21m^3,mKMP_m^ *mIYL_Ym GGFm .#9(OO'/.#)(-O Resultados m m (&30 TDMBCOT*9,23*1mHm"#m*m$+'*'m+32,2#mINJYm#m- 1#04Am3,m$#,-2'.-m!0!2#0>12'!-m!-,1'12#,2#m#,mm#*m 3*2+'#,2-m"#m*-1m!-2'*#"-,#1m^$*#!&1m83*#1_Ymm m *m 1#!3#,!'0m *-1m GKm ',"'4'"3-1m %#0+',"-1m "#m *m $+'*'m INJm - 234'+-1m Lm &-+-!'%-2-1m 1'*4#120#1m 7m Om &#2#0-!'%-2-1m ^ *m IYMZm #6.#0'+#,2-m G_Ym -m #,!-,20+-1m ,',%B,m&-+-!'%-2-m+32,2#Zm3,/3#m&7m/3#m2#,#0m#,m!3#,2m/3#m,-m.3"'+-1m0#!-%#0m +2#0'*m "#m *m .*,2m /3#m +30'Am #,m #12"'-m "#m !-2'*#"A,Ym -m 1#m .3"-m #12 *#!#0m 3,m 0#*!'A,m"'0#!2m!-,m#*m$#,-2'.-m"#2#!2"-m#,m#12m$+'*'m7m#*m%#,-2'.-m"#m*-1m',"'4'"3-1m ^'%30m IYGH_Ym 1m .-0m #**-m /3#m 1#m "#!'"'Am 0#.#2'0m #*m #6.#0'+#,2-m ^#6.#0'+#,2-m H_m .0m ',2#,20m0#!-%#0m+2#0'*m"#m#11m.*9,23*1m/3#m1#m+-0>,m.0#+230+#,2#Ymm 0m #**-Zm 1#m %#0+',0-,m HFm 1#+'**1m Im /3#m 1#m & >,m - 2#,'"-m "#m 3,m .*,2m Hm &#2#0-!'%-2m.0m*m+32!'A,Ym#m- 234'#0-,mGKm.*,21Zm*-m/3#m0#.0#1#,2m3,m.-0!#,2(#m "#m %#0+',!'A,m "#*m MKPYm *m $#,-2'.-m - 1#04"-m ,2#0'-0+#,2#m ^&-(1m 1#!1Zm 3*2"1_m 1#m0#.'2'Am.#0-m"#+91m#12m4#8m1#m- 234-m3,m.*,2m* ',Ymm m GGGm .#9(OO'/.#)(-O Resultados !+ T DMH[m #13*2"-1m "#m *m 1#%0#%!'A,m "#m *m +32!'A,m #,m *1m $+'*'1m +32,2#1m "#m *m Ym #2**#m "#m *-1m ',"'4'"3-1m#,!-,20"-1m#,m!"m!*1#m%#,-2>.'!m7m*-1m"2-1m"#*m2#12m"#m"#O/,)O^sH_m!-,m13m.0- '*'""Ym 0m *m $+'*'m INJm 1# 0#*'80-,m "-1m #6.#0'+#,2-1Ym ,m #* .0'+#0-Zm 0#*'8"-m #, *m %#,#0!'A,m HZ ,-m - 234'+-1m ,',%B,m &-+-!'%-2-m +32,2#Zm 3,/3#m 1#m +30'Am 3,m .*9,23*m ,2#1m "#m .-"#0m 0#!-%#0m +2#0'*Ym *m 1#%3,"-m #6.#0'+#,2-m 1#m 0#*'8Am !-,m *m %#,#0!'A,m IZm #,m *m !3*m 1'm - 234'+-1m 3,m +32,2#m &-+-!'%-2-m /3#m !-',!'"'Am!-,m#*mB,'!-m$#,-2'.-m* ',-Ym m ,(+( T 52R52T PGCSBBDQT 52R,T ,R,T 2 T 0.! !(+(# #T GGKGm Jm Mm Jm FZFGLMm TFZOm INJm^#6.#0'+#,2-mGZmH_m Lm Om jm HZOm FZKjFZGm INJm^#6.#0'+#,2-mHZmI_m GJm m Gm Nm FZFGm m #m 0#!-%'Am +2#0'*m "#m *m &-(m 7m 1#m %#,-2'.0-,m GKm ',"'4'"3-1Ym 12m 4#8m #*m ,B+#0-m "#m &-+-!'%-2-1m 1'*4#120#1m ^LHjGGI_m $3#m "#m GJZm ,',%3,m .*,2m 0#13*2Am &#2#0-!'%-2m 7m .3"'+-1m4#0'$'!0m+#"',2#m1#!3#,!'!'A,m/3#m*mB,'!m.*,2m&-+-!'%-2m+32,2#m#0m *m.*,2m!-,m$#,-2'.-m* ',-Zm2*m7m!-+-m.3#"#m4#01#m#,m*m'%30mIYGIYm m m m (&30 TDMBD[m ,m #*m !#,20-Zm *-1m !0-+2-%0+1m - 2#,'"-1m *m 1#!3#,!'0m #*m $0%+#,2-m "#*m %#,m "#m *m m #,m *-1m "'12',2-1m',"'4'"3-1m"#m*m$+'*'m+32,2#mINJYm3#"#m- 1#0401#m^"#m00' m (-_m#*m%#,-2'.-m&-+-!'%-2-m +32,2#m/3#m!-00#1.-,"#mm*m.*,2mIm* ',m^'+9%#,#1m#,m*-1m*2#0*#1_Zm#*m%#,-2'.-m&-+-!'%-2-m1'*4#120#Zm7m $',*+#,2#m #*m %#,-2'.-m &#2#0-!'%-2-Ym m .*,2m * ',m $3#m #*m B,'!-m ',"'4'"3-m &-+-!'%-2-m .0m *m +32!'A,m #,!-,20"-m#,m*m$+'*'mINJYm^[m32,2#Zm[m'*4#120#_Ym m T GGHm .#9(OO'/.#)(-O Resultados T DMCMCT!$PTTTTTQT 1m 0#1'12#,!'1m 0#!#1'41m #,m .*,21m &,m 1'"-m +.*'+#,2#m ',4#12'%"1m 4'<,"-1#m /3#m *-1m $!2-0#1m "#m ','!'!'A,m "#m *m 20"3!!'A,m ^>Jm #129,m "'0#!2+#,2#m 0#*!'-,"-1m !-,m *%3,1m 0#1'12#,!'1m m 4'031m 7m +91m !-,!0#2+#,2#m m *-1m .-2'4'031m ^- %*'m 7m 0,2Zm HFFL\m 3$$#*m 7m !-*YZm HFFJ_Ym ,m ,3#120-m * -02-0'-m "'1.-,>+-1m "#m *m 1#!3#,!'m "#*m %#,m >O^3,'%#,m3mKJLIOZm,B+#0-m"#m!!#1'A,mKMOMF_m7m*-1m!# "-0#1m.0m#*m ,9*'1'1m#12 ,m7m"'1#@"-1m.0m!-m^'#2-m7m!-*ZmHFFM_Ym-0m#**-Zm1#m310-,m *-1m +'1+-1m !# "-0#1m /3#m .#0+'2>,m #*m ,9*'1'1m "#*m %#,m #,m "-1m +.*'!-,#1Z 3,m .0'+#0m +.*'!A,m /3#m 0! m KFFm . m 7m .#0+'2>m +.*'$'!0m #*m .0'+#0m #6A,m 7m 3,m 1#%3,"-m +.*'!A,m"#mGGLOm. m/3#m.#0+'2>m,*'80m"#*m1#%3,"-m*m/3',2-m#6A,m^'%30mIYGJ_Ymm m (&30 TDMBEOT#.0#1#,2!'A,m"#*m%#,m>m#,m+#*A,m^(-0_Ym,m*m.02#m13.#0'-0m1#m+3#120,m*-1m"-1m+.*'!-,#1m 31"-1m"#mKFFm7mGGLOm. Ym-1m20'9,%3*-1m"#2**,m*1m.-1'!'-,#1m#,m*1m/3#m1#m&,m#,!-,20"-m+32!'-,#1Ym,m 0-(-Zm*-1m+32,2#1m#,!-,20"-1m#,m*m.- *!'A,m"#*mm7m#,m4#0"#m*-1m+32,2#1m#,!-,20"-1m#,m*m.- *!'A,m "#*mYm,m0-(-m7m+0'**-m*1m0#%'-,#1mKdm7mIdmZm0#1.#!2'4+#,2#Ym m 1m'+.-02,2#m+#,!'-,0m/3#m%0!'1mm*m0#!'#,2#m- 2#,!'A,m"#m*m1#!3#,!'m"#*m%#,-+m "#*m+#*A,m^0!'j1m7m!-*YZmHFGH_m1#m&m.-"'"-m!-,$'0+0m/3#m1A*-m#6'12#m3,m!-.'m"#*m %#,m>m#,m#12m#1.#!'#m^'%30mIYGK_Zmm"'$#0#,!'m"#m,#)*-#-O."&#(m/3#m!-,2'#,#mIm %#,#1Zm -m Hm #,m 2-+2#Ym 1m 20#1m #1.#!'#1Zm 1',m #+ 0%-Zm 1A*-m 2'#,#,m 3,m !-.'m "#m *m '1-$-0+mI#-)J>m^-"0>%3#8j#0,9,"#8m7m!-*YZmHFGH_Ym m GGIm Resultados m .#9(OO'/.#)(-O m (&30 TDMBFOm0 -*m$'*-%#,<2'!-m"#*m%#,m>Ymm*m"#0#!&m1#m- 1#04m*m1#!!'A,m+.*'"m"-,"#m1#m*-!*'8m #12#m %#,m "#m +#*A,m ^$*#!&m 0-(_Ym #m .3#"#m - 1#040m /3#m 1A*-m &7m 3,m !-.'m ^$3#,2#[m &7*-+#" Y-0%_m 1',m #+ 0%-Zm,#)*-#-O."&#(m!-,2'#,#m20#1m!-.'1m^$*#!&1m83*#1_Ym T DMCMCMBTNTTTTTTTTTT!T 0m #*m .0'+#0m +.*'!A,m ^ *m IYN_m 1#m "#2#!2Am 3,m +32,2#m #,m *m .- *!'A,m "#*m m ^HFILZm +32,2#m ,Em G_m 7m 20#1m #,m *m .- *!'A,m "#*m m ^KIm ^K_Zm HKIHm ^L_m 7m GJHFm ^M__Ym -1m +32,2#1mGZmKm7mLm2'#,#,m*m+32!'A,m#,m#*m.0'+#0m#6A,m+'#,201m/3#m#*m+32,2#mMm2'#,#m *m +32!'A,m #,m *m 0#%'A,m "#*m .0'+#0m ',20A,m 3,/3#m +37m !#0!,m *m $',*m "#*m #6A,Ym *m 1#!3#,!'0m*-1m1m1#m&m!-+.0- "-m/3#m2-"-1m*-1m!+ '-1m#6!#.2-m"-1m^+32,2#mJZm OKOZmim7m+32,2#mGFZm$+'*'mGHNMZmi_Zm1-,m20,1'!'-,#1m"#mimmiZm2*m7m!A+-m #0m#1.#0"-m*m310mYm#m*1m20#1m+32!'-,#1m"#1!0'21m#,m#*m#6A,mGZm"-1m.0-4-!,m !+ '-m"#m+',-9!'"-m1',m#+ 0%-Zm#*mm"#*m+32,2#mLm#1m1'*#,!'-1-Ym1m+32!'-,#1m "#*m+32,2#mGm^HK_m7m"#*m+32,2#mKm^OM_m.0-4-!,m1312'23!'-,#1m'+.-02,2#1m.0m *m$3,!'-,*'""m"#m*m.0-2#>,m1#%B,mYmm T GGJm .#9(OO'/.#)(-O Resultados !+ TDMIOT32,2#1m#,!-,20"-1m#,m#*m.0'+#0m+.*'!A,m"#mKFFm. m"#*m%#,m>Ym,m0-(-Zm/3<**-1m#,!-,20"-1m #,m*m.- *!'A,mm7m#,m4#0"#m#,m*m.- *!'A,mYmg-1'!'A,m0#1.#!2-m#*mm#,m#*m+Ym m Nº Familia Posición CDS* Cambio aa %EMS SIFT 1 F2036 Exón 1 G 74 A Arg25Lys 1% 0.00 0.02 5 53 Exón 1 G 289 A Glu97Lys 1% 6 2532 Exón 1 C 294 T Phe98Phe 2% 7 1420 Intrón 1 G/A 2% 0m #*m 1#%3,"-m +.*'!A,m ^ *m IYO_m 1#m '"#,2'$'!0-,m 3,m 2-2*m "#m GJm +32,2#1m "#m *-1m !3*#1mGGm1#m&,m"#2#!2"-m#,m*m.- *!'A,m"#*mm7mIm#,m*m.- *!'A,m"#*mYm#m #12-1Zm Km 2'#,#,m *m +32!'A,m #,m 0#%'A,m #6A,'!Zm Mm #,m 0#%'A,m ',20A,'!m 7m Hm #,m #*m #620#+-m IaYm 320-m "#m *-1m +32,2#1m /3#m 2'#,#,m *m +32!'A,m #,m *m 0#%'A,m #6A,'!Zm .0-4-!,m 3,m !+ '-m "#m +',-9!'"-m ^KMZm GHHOZm JJJZm HFLF_m 7m *m $+'*'m GNNFm !-,2'#,#m 3,m +32!'A,m1'*#,!'-1Ym m$+'*'mGLLMm!-,2'#,#m#*mm#,m#*m.0'+#0m,3!*#A2'"-m"-,"#m#+.'#8m#*m',20A,mIZm.-0m *-m2,2-Zm.-"0>m4#01#m$#!2"m*m$3,!'A,m"#m-*&##(!O7m#,m!-,1#!3#,!'m*m$3,!'-,*'""m "#m *m .0-2#>,Ym -"1m *1m +32!'-,#1m '"#,2'$'!"1m #,m #12#m +.*'!A,m 1-,m 20,1'!'-,#1m ijim#6!#.2-m#,mOKOZm#,m#*m/3#m#*m!+ '-m#1m3,m20,14#01'A,m"#m%3,',mm!'2-1',m 7mGILNZm/3#m!-,2'#,#m3,m!+ '-m"#m2'+',mm!'2-1',Ym m !+ T DMJOT 32,2#1m '"#,2'$'!"-1m #,m #*m 1#%3,"-m +.*'!A,m "#m GGLOm . m "#*m %#,m >Ym ,m 0-(-Zm /3<**-1m #,!-,20"-1m#,m*m.- *!'A,mm7m#,m4#0"#m#,m*m.- *!'A,mYmm m Nº Familia Posición CDS Cambio aa %EMS SIFT 2 F57 Exón 2 G 385 A Glu129Lys 1% 0.00 3 F1880 Exón 2 G 465 A Thr155Thr 1% 4 F959 Intrón 2 G/C 8 1229 Exón 2 C 401 T Ala134Val 2% 0.10 9 444 Exón 2 G 407 A Gly136Glu 2% 0.00 10 1287 Intrón 2 C/A 2% 11 1115 Intrón 2 C/T 2% 12 1667 Intrón 3 G/A primer nucleótido del intrón 2% 13 2646 Intrón 3 C/T 2% 14 1233 Intrón 3 C/T 15 2060 Exón 4 G 616 A 1% 2% Glu206Lys 2% 0.09 GGKm .#9(OO'/.#)(-O Resultados 16 2035 Intrón 4 C/T 2% 17 1368 3’UTR T/C 2% 18 2163 3’UTR G/A 2% m ,m 0#13+#,Zm #,m #*m %#,m >m 1#m &,m #,!-,20"-m 3,m 2-2*m "#m GNm +32,2#1m 2#,'#,"-m #,m !3#,2m*-1m0#13*2"-1m"#m*-1m"-1m+.*'!-,#1Ym!&-m"#m#**-1m^JJZJP_m#,m0#%'A,m#6A,'!ZmNm #,m0#%'A,m',20A,'!m^JJZJP_m7mHm#,m#*m#620#+-mIam^GGZGGP_Ym#m*-1m+32,2#1m#,m0#%'A,m #6A,'!Zm Im ^IMZKP_m .#02#,#!#,m m *m .- *!'A,m "#*m m +'#,201m /3#m Km ^LHZKP_m m *m .- *!'A,m"#*mYm,m*m'%30mIYGLm1#m.0#1#,2m#*m*',#+'#,2-m#,20#m#*m%#,m>m7m 13m '1-$-0+Zm I#-)J>Zm "#m +-"-m /3#m .3#"#m - 1#0401#m *m &-+-*-%>m #,20#m + -1m 7m "#+91m *m *-!*'8!'A,m "#m *1m +32!'-,#1m '"#,2'$'!"1m #,m #*m .0'+#0-m "#m #**-1m #,m .-1'!'-,#1m #6A,'!1Ym *%3,1m "#m #121m +32!'-,#1m #129,m *-!*'8"1m #,m 0#%'-,#1m +37m !-,1#04"1m.0m+ -1m%#,#1Ym m m (&30 T DMBGOT *',#+'#,2-m #,20#m *1m .0-2#>,1m "#m >m 7m #*m I#-)J>m "#m +#*A,m ',"'!,"-m *1m +32!'-,#1m "#2#!2"1m#,m>m^*1m4#0"#1m!-00#1.-,"'#,2#1mm+32!'-,#1m"#2#!2"1m#,m$+'*'1m"#m*m.- *!'A,mm7m *1m0-(1m#,m*m.- *!'A,m_Ym m 1m'+.-02,2#m"#12!0m/3#m"#m*1m!320-m$+'*'1m+32,2#1m"#2#!2"1m#,m*m.- *!'A,m "#*m Zm Im 2'#,#,m *m +32!'A,m #,m 0#%'A,m #6A,'!m ^MKP_Ym ',m #+ 0%-Zm #,m *m .- *!'A,m "#*m Zm "#m 3,m 2-2*m "#m GJm $+'*'1m +32,2#1m 1A*-m Km 1#m *-!*'8,m #,m 0#%'A,m #6A,'!m ^IKZMP_Ymm #%B,m *-1m 4*-0#1m "#m Zm *1m +32!'-,#1m /3#m $#!20,m m *m $3,!'-,*'""m "#m *m .0-2#>,m1#09,m*1m"#m*1m$+'*'1mHFILZmKIZmKMm7mJJJZm+'#,201m/3#m*1m+32!'-,#1m"#m GGLm .#9(OO'/.#)(-O Resultados *1m$+'*'1mGHHOm7mHFLFm1#09,m2-*#0"1m1#%B,mm^4*-0TFZFK_m7m*m$3,!'-,*'""m"#m*m .0-2#>,m ,-m 1#m 4#09m $#!2"Ym #1.#!2-m m *m "'120' 3!'A,m "#m *1m +32!'-,#1m "# #+-1m "#12!0m/3#m1#m&,m#,!-,20"-m+32,2#1m#,m2-"-1m*-1m#6-,#1m#6!#.2-m#,m#*m#6A,mIYm-0m -20-m *"-Zm *m "'120' 3!'A,m "#m *1m +32!'-,#1m #,m *1m .02#1m ',20A,'!1m ,*'8"1m .0#!#m 1#0m&-+-%<,#Ym m DMCMCMCTTTTTTDTTTT!T 0m !-+.*#+#,20m *-1m #123"'-1m "#m .0#"'!!'A,m !-,m m "#m !A+-m .3#"#,m $#!20m *1m 1312'23!'-,#1m +',-!>"'!1m m *m $3,!'-,*'""m "#m *m .0-2#>,m "#*m %#,m >Zm 1#m 0#*'8Am 3,m#123"'-m"#2**"-m"#m*m#1203!230m#,mIm"#m>Em*m%#,m>m2'#,#m3,m%0,m',2#0<1m .3#12-m /3#m *m - 2#,!'A,m "#m 3,m 40'#""m 0#1'12#,2#m m "#2#0+',"-1m 4'031m 1#0>m 3,m &**8%-m'+.-02,2#m2,2-mm,'4#*m!'#,2>$'!-m!A+-m!-+#0!'*Ym-0m#12#m+-2'4-m0#*'8+-1m 3,m #123"'-m +91m #6&312'4-m "#m .0#"'!!'A,m "#m !A+-m .-">,m $#!20m *1m +32!'-,#1m "#2#!2"1m m *m #1203!230m "#m >Ym *m +-"#*(#m #,m Im 1#m 0#*'8Am !-,m #*m .0-%0+m '-',$-0+92'!-m 7Ym ,m *1m $'%301m /3#m 1#m .0#1#,2,m m !-,2',3!'A,m 1#m .3#"#,m 4'13*'80m *1m *-!*'8!'-,#1m "#m *1m +32!'-,#1m '"#,2'$'!"1m /3#m .-"0>,m $#!20m m *m $3,!'-,*'""m"#m>Em *m+32,2#m,B+#0-mHm^$+'*'mKMZm+32!'A,m*3GHO71_m^1#%B,m *mIYO_m^'%30mIYGM_m .0#!#m !-,2#,#0m *m +32!'A,m +91m '+.-02,2#m #,m !3,2-m *m .-1' *#m #$#!2-m 1- 0#m *1m ',2#0!!'-,#1m#,20#m*m.0-2#>,m7m13m*'%,"-Ym30,2#m#*m+-"#*(#m1#m#12 *#!'Am*m.-1' *#m 8-,m "#m ',2#0!!'A,m #,20#m >m 7m #*m KaZm 7m /3#m 7m -$0#!>m *m .-1' '*'""m "#m "#$','0m4'023*+#,2#m^m204<1m"#m!-+.0!'-,#1m!-,m*1m 1#1m"#m"2-1m"#m!0'12*'8!'A,m "#m3,'-,#1m"#m.0-2#>,1m!-,m13m131202-m-m*'%,"-_m#*m!#,20-m!2'4-m7m#*m*'%,"-m^'%30m IYGN_Ym,m#12#m!1-m#*m*'%,"-m#1m*mMj+#2'*m%3,-1',m20'$-1$2-m^GGGNKGGHQ_m-mKaZm +-*<!3*m /3#m 1#m @"#m *m +m 7m *-m .0-2#%#m "#m 13m "#%0"!'A,Ym 12m +-*<!3*m #1m #*m *3%0m"#m0#!-,-!'+'#,2-m.0m#*m','!'-m"#m*m20"3!!'A,m7m.-0m*-m2,2-m*m/3#m',2#0!!'-,m "'0#!2+#,2#m!-,m*m.0-2#>,m>m#,m#*m+-+#,2-m"#*m','!'-m"#m*m20"3!!'A,m^- %*'m 7m 0,2Zm HFFL_Ym 12m +32!'A,m #1m #1.#!'*+#,2#m ',2#0#1,2#m .-0/3<m .0#!#m /3#m - *'%0>m m #12 *#!#0m #,*!#1m "'12',2-1m !-,m #*m *'%,"-Zm *-m /3#m .-"0>m 2#,#0m #$#!2-m #,m *m $3,!'-,*'""m"#m>Ymm m GGMm .#9(OO'/.#)(-O Resultados T T (&30 T DMBH[m -"#*(#m "#m *m .0-2#>,m >m #,m Im +#"',2#m #*m /.*/.O "#*m .0-%0+m 7m "#*m +32,2#m Hm ^$+'*'mKM_Ym,m0-(-m7m+0!"m+#"',2#m*m$*#!&Zm*m.-1'!'A,m"#m*m+32!'A,m*3GHO71Ym m m m (&30 T DMBI[m -"#*(#m "#m *m .0-2#>,m >m #,m Im +#"',2#m #*m /.*/.O "#*m .0-%0+m 7m !-,m .-1' *#m *'%,"-m ^+-*<!3*m Kdm "#*m +_Ym ,m +0'**-Zm "#2**#m "#m *1m .-1' *#1m ',2#0!!'-,#1m #,20#m #*m *'%,"-m ^#,m 0-(-_m7m#*m+',-9!'"-m*3GHOm^#,m0-(-m7m$*#!&_Ym m *m +32,2#m ,B+#0-m Km ^$+'*'m KIZm +32!'A,m *3OM71_m ^1#%B,m *m IYN_m ^'%30m IYGO_m !-,2'#,#m 3,m +32!'A,m /3#m .3#"#m .0-4-!0m 3,m #$#!2-m !-+.0-+#2'"-m .0m *m $3,!'-,*'""m "#m *m .0-2#>,Ym *m 9!'"-m %*329+'!-m "#m *m .-1'!'A,m OMm #,m #*m %#,-2'.-m 1'*4#120#m !0#m 3,m #,*!#m "#m &'"0A%#,-m !-,m *m 1#0',m OIm ^'%30m IYHF_Ym ,m !+ '-Zm #,m #*m +32,2#m #*m 9!'"-m %*329+'!-m /3#"m 1312'23'"-m .-0m 3,m *'1',m 7m <12m .10>m m GGNm .#9(OO'/.#)(-O Resultados ',2#0!!'-,0m !-,m *m 20#-,',m *-!*'8"m #,m *m .-1'!'A,m OGYm -0m *-m 2,2-Zm *m +32!'A,m .0-"3!'0>m 3,m !+ '-m #,m *1m ',2#0!!'-,#1m #,20#m +',-9!'"-1m 7m .-"0>m $#!20m *m #1203!230m-m*m#12 '*'""m"#m>Ymm m m m (&30 T DMBJ[m -"#*(#m "#m *m .0-2#>,m >m #,m Im +#"',2#m #*m /.*/.O "#*m .0-%0+m 7m "#*m +32,2#m KZm $+'*'mKIYm,m0-(-m7m+0!"m+#"',2#m*m$*#!&Zmm*m.-1'!'A,m"#m*m+32!'A,m*3OM71Ym m m T (&30 TDMCAOm/.*/.O"#*m.0-%0+m7m"#*m+32,2#mKZm$+'*'mKIYm#2**#m"#m!A+-m!+ '0>m#*m#,*!#m#,m#*m +32,2#Ym ,m #*m %#,-2'.-m 1'*4#120#m ',2#0!!'-,m #*m 9!'"-m %*329+'!-jOMm !-,m *m 1#0',jOIm 7m #,m !+ '-Zm #,m #*m +32,2#m',2#0!!'-,0>m*m*'1',jOMm!-,m*m20#-,',jOGYm *m +32,2#m ,B+#0-m Nm ^$+'*'m GHHOZm +32!'A,m *GIJ*_m ^1#%B,m *m IYO_m 2'#,#m *m +32!'A,m*-!*'8"m#,m*m13.#0$'!'#m"#m>m^'%30mIYHG_m.-0m*-m/3#m13m#$#!2-m"# #0>m 1#0m +#,-0m .3#12-m /3#m #*m !#,20-m !2'4-m "#m >m 1#m *-!*'8m #,m 3,m .-1'!'A,m ',2#0,Ym GGOm .#9(OO'/.#)(-O Resultados "#+91Zm*m4*',m7m*m*,',m,-m.-1##,m!0%Zm7m.-0m*-m2,2-m*m1312'23!'A,m,-m2#,"0>m .0- *#+#,2#m,',%B,m#$#!2-mm,'4#*m#1203!230*Ym m (&30 T DMCB -"#*(#m "#m *m .0-2#>,m > #,m Im +#"',2#m #*m 32.32m "#*m .0-%0+m 7m "#*m +32,2#m NZ $+'*'mGHHOYm,m0-(-m7m+0!"m+#"',2#m*m$*#!&Zm*m.-1'!'A,m"#m*m+32!'A,m*GIJ*YT m *m+32,2#m,B+#0-mOm^$+'*'mJJJZm+32!'A,m*7GIL*3_m^1#%B,m *mIYO_m',20-"3!#m3,m !+ '-m"#m%*'!',mm9!'"-m%*329+'!-Zmm3,m0#1'"3-m"#m!"#,m*0%m*2#0*m!-,m!0%Ymm .-1'!'A,m"#m#12#m0#1'"3-m,-m#1m13.#0$'!'*m1',-m',2#0,m^'%30mIYHH_Ymm m T T (&30 T DMCC[m -"#*(#m "#m *m .0-2#>,m >m #,m Im +#"',2#m #*m /.*/.O "#*m .0-%0+m 7m "#*m +32,2#m OZm $+'*'mJJJYm,m$3!1'm7m+0!"m+#"',2#m*m$*#!&Zm*m+32!'A,m*7GIL*3Ym GHFm .#9(OO'/.#)(-O Resultados m #m&,m',!*3'"-m#,m*m'%30mIYHIm2-"1m*1m+32!'-,#1m!-+#,2"1m,2#0'-0+#,2#m.0m #*m%#,m>Ym1m+32!'-,#1mGm7mGKm,-m1#m,*'80-,Ymmm m T (&30 TDMCDOm-"#*(#m"#m*m.0-2#>,m#,mIm"#*m%#,m>Ym,m0-(-m*1m+32!'-,#1m"#2**"1m,2#0'-0+#,2#m.-0m 13m.-1' *#m'+.*'!!'A,m#,m#*m!+ '-m"#m$3,!'-,*'""m"#m>Em T DMCMDT "#!T PT T T T T T T TEQT ,m #*m * -02-0'-m 7m 1#m & >m ','!'"-m *m 1#!3#,!'!'A,m "#*m %#,m I#-)J>m ^3,'%#,m JJOFGm "#m *m 1#m "#m "2-1m "#m 3_m 7m .-0m *-m 2,2-m "'1.-,>+-1m "#m 3,m .02#m '+.-02,2#m "#m *m 1#!3#,!'Ym 3,m 7m 1>Zm 1#m "'1#@0-,m !320-m ,3#4-1m !# "-0#1m ^'%30m IYHJm _m .0m .-"#0m 2#0+',0m "#m 1#!3#,!'0m *-1m $0%+#,2-1m /3#m $*2 ,m .0m - 2#,#0m *m 1#!3#,!'m!-+.*#2Ym,m4#8m- 2#,'"Zm0#1#!3#,!'+-1m#,m*m40'#""mLHjGGIYm,m#1#m +-+#,2-m ,-m 1#m & >m .3 *'!"-m 2-"4>m *m 1#!3#,!'m !-+.*#2m "#*m %#,Zm 1',m #+ 0%-Zm !23*+#,2#m 1'm #129m "'1.-,' *#(#,#,)[m HIHGMHm ^1#!3#,!'m "#*m m /3#m !-,2'#,#m I#-)J>m#,m*m0#%'A,[mOOIKjGGOGJ__m^#7#0m7m!-*YZmHFFN_Ym#!'"'+-1m','!'0m*m"#2#!!'A,m "#m*-1m+32,2#1m31,"-m3,m+.*'!A,m#,m*m0#%'A,m"#*m%#,m"#2**"m#,m*m'%30mIYHJZm"#m GFGJm. m7m/3#m!-,2#,>m20#1m#6-,#1Y m GHGm Resultados .#9(OO'/.#)(-O T T (&30 T DMCEOT ^ _T 1/3#+m "#*m %#,m I#-)J>m !-+.3#12-m "#m !',!-m #6-,#1m ^!(1m 83*#1_Ym + '<,m .3#"#m - 1#0401#m ^!_m #*m $0%+#,2-m ,*'8"-m +#"',2#m m "#m GFGJm . m 1>m !-+-m ^_m *-1m !# "-0#1m 32'*'8"-1m 2,2-m .0m 1#!3#,!'0m *m 0#%'A,m !-+-m .0m "#2#!20m *-1m +32,2#1m ^,#6-m Y(_Ym -1m 20'9,%3*-1m "#2**,m *1m .-1'!'-,#1m#,m*1m/3#m1#m&,m#,!-,20"-m+32!'-,#1Ym,m4#0"#m*-1m+32,2#1m#,!-,20"-1m#,m*m.- *!'A,m"#*m Ym T !23*+#,2#m #12#m %#,m &m 1'"-m '"#,2'$'!"-m #,m *m 1#!3#,!'m "#*m %#,-+m !-+-m IFHIFIMm!-,m3,m*-,%'23"m2-2*m"#mGOOGm. Ym*m7m!-+-m1#m&m.-"'"-m- 1#040m#,m *m '%30m IYGLZm *-1m %#,#1m >m 7m 13m '1-$-0+m !-,2'#,#,m 0#%'-,#1m +37m !-,1#04"1Ym + '<,m %0!'1m m *m - 2#,!'A,m "#m *m 1#!3#,!'m "#*m %#,-+m "#*m +#*A,m ^0!'j1m 7m !-*YZm HFGH_m 1#m &m .-"'"-m !-,$'0+0m /3#m 1A*-m #6'12#m 3,m !-.'m "#*m %#,m I#-)J>m ^'%30m IYHK_Ym m (&30 T DMCFOm 0 -*m $'*-%#,<2'!-m "#*m %#,m I#-)J>Ym m *m "#0#!&m 1#m - 1#04m *m 1#!!'A,m +.*'"m "-,"#m 1#m *-!*'8m #12#m %#,m "#m +#*A,m ^$*#!&m 0-(_Ym #m .3#"#m - 1#040m /3#m 1A*-m &7m 3,m !-.'m ,-2"m #,m #*m %#,-+m ^$3#,2#[m&7*-+#" Y-0%_Ym GHHm .#9(OO'/.#)(-O Resultados m DMCMDMBTNTTTTTTT ,m #*m %#,m I#-)J>m 1#m &m '"#,2'$'!"-m 3,m B,'!-m +32,2#m #,m *m .- *!'A,m m 7m ,',%3,-m#,m*m.- *!'A,mm^ *mIYGF_Ym*m+32,2#m"#2#!2"-m.#02#,#!#mm*m$+'*'m GKNMm 7m 2'#,#m 3,m m #,m #*m .0'+#0m #6A,m "#*m %#,Ym 12m +32!'A,m .0-4-!m 3,m !+ '-m "#m +',-9!'"-m "#m 0%',',m m *'1',Zm 1',m #+ 0%-Zm 1#%B,m *-1m 4*-0#1m - 2#,'"-1m #,m Zm .-"0> 1#0m2-*#0"-m7m,-m$#!20mm*m$3,!'A,m"#m*m.0-2#>,Ym m !+ TDMBAOT0!2#0>12'!1m"#*m+32,2#m#,!-,20"-m#,m#*m%#,mI#-)J> #,m*m.- *!'A,m"#mm!-,m#*m,-+ 0#m "#m*m$+'*'Zm.-1'!'A,Zm2'.-m"#m+32!'A,m7mPm"#mm32'*'8"-Ymm+32!'A,m1#%B,mm,-m#1m1'%,'$'!2'4m7m ,-m$#!20>mm*m$3,!'A,m"#m*m.0-2#>,Yg-1'!'A,m0#1.#!2-m*m!# "-0m'1-JYm m Nº Familia Posición CDS * Cambio aa %EMS SIFT 1 M1587 Exón1 G128A Arg43Lys 2% 1.00 T m DMCMET TPTTTBQT *m ; ^#!#.2-0m "#m 2'*#,-m G_m .#02#,#!#m m 3,m $+'*'m +3*2'%<,'!m ^2-j0m 7m !-*Zm GOOO_m7m#129m'+.*'!"-m#,m*m1#@*m"#m20,1"3!!'A,m"#*m#2'*#,-m^*##!)#0m7m#,"#ZmHFFF_Ym 129,m "#1!0'21m +32!'-,#1m #,m #12#m %#,m #,m ,#)*-#-O /3#m .0-4-!,m ',1#,1' '*'""m *m #2'*#,-m ^'*)',1-,m 7m !-*YZm GOOK_m 7m 2+ '<,m 1#m &m "#+-120"-m /3#m &7m 3,m +7-0m #6.0#1'A,m"#m#12#m%#,m#,m1#+'**1m7m.*!#,2m^2-j0m7m!-*YZmGOOO_Ym,m*m 1#m"#m"2-1m ^&22.[ii555Y'!3%'Y-0%_m "'1.-,>+-1m "#*m 3,'%#,m JNJOOm "#1!0'2-m !-+-m .02#m "#*m %#,m ;Zm.-0m#**-m1#m','!'Am*m1#!3#,!'!'A,mm.02'0m"#m#12#mYm',*+#,2#Zm1#!3#,!'+-1m 3,m%0,m.02#m"#*m%#,m32'*'8,"-mGIm!# "-0#1m#,m"'12',21m!-+ ',!'-,#1Zm"#2**"-1m #,m*m'%30mIYHLYm m (&30 TDMCGOT1/3#+m"#*m%#,m;m^ _Zm"#m*-1m!# "-0#1m"'1#@"-1m.0m13m1#!3#,!'!'A,m^_m^,#6-mY(_m7m"#*m $0%+#,2-m"#*m%#,m"#mLGKm. m,*'8"-m+#"',2#mm^!_Ym m !23*+#,2#m1#m&m.-"'"-m- 2#,#0m*m1#!3#,!'m!-+.*#2m"#*m%#,m;O#,m+#*A,Ym*m%#,m '"#,2'$'!"-m!-+-mIFFIOFLm2'#,#m3,m*-,%'23"m2-2*m"#mJONNm. m7m#129m!-+.3#12-m GHIm T Resultados .#9(OO'/.#)(-O .-0m 1#'1m #6-,#1m 2*m 7m !-+-m 1#m & >m '"#,2'$'!"-m +#"',2#m *m 1#!3#,!'!'A,m #,m *m 40'#""mLHjGGIYm-+-m#,m*-1m%#,#1m.0#1#,2"-1m,2#0'-0+#,2#Zm2+ '<,m1#m&m.-"'"-m - 2#,#0m#*m90 -*m$'*-%#,<2'!-m"#*m%#,m;m!-+.0- ,"-m/3#m$-0+m.02#m"#m3,m$+'*'m +3*2'%<,'!m7m!-+-m2*Zm#,!-,20+-1m"-1m%#,#1m.09*-%-1m#,m+#*A,m^'%30mIYHM_Ym m m T (&30 TDMCHOm0 -*m$'*-%#,<2'!-m"#*m%#,m;Ymm*m"#0#!&m1#m- 1#04m*m1#!!'A,m+.*'"m"-,"#m1#m*-!*'8m #12#m%#,m"#m+#*A,m^$*#!&m0-(_Ym#m.3#"#,m- 1#040mm*m'8/3'#0"m^1#@*"-1m!-,m$*#!&1m83*#1_m*-1m.09*-%-1m *m%#,m;m^$*#!&m0-(_m^$3#,2#[m&7*-+#" Y-0%_Ym T DMCMEMBTNTTTTTTT 01m #*m ,9*'1'1m +#"',2#m m "#*m %#,m ;m ,-m 1#m "#2#!20-,m +32,2#1m #,m *m .- *!'A,m "#*m Ym -0m -20-m *"-Zm #,m *m .- *!'A,m "#*m m ,-m 1#m .3"-m ,*'80m #12#m %#,m .3#12-m /3#m *-1m !# "-0#1m "'1#@"-1m m .02'0m "#m *m 40'#""m 31"m #,m *m .- *!'A,m Zm ,-m $3,!'-,0-,m !-00#!2+#,2#m 7m ,-m +.*'$'!0-,m #,m *m 40'#""m ",(.#-Ym #m "'1#@0-,m ,3#4-1m !# "-0#1m 3,/3#m 1'#+.0#m m .02'0m "#m *m 1#!3#,!'m "#m 0#$#0#,!'m GHJm .#9(OO'/.#)(-O Resultados - 2#,'"m"#m*m40'#""mLHjGGIYm12#m1#%3,"-m"'1#@-m"#m!# "-0#1m2+.-!-m+.*'$'!Am *m40'#""m",(.#-Ym',*+#,2#Zm,-m&3 -m+91m2'#+.-m.0m,*'80m!39*m#0m#*m+-2'4-m .-0m#*m!39*m*-1m!# "-0#1m,-m&' 0'" ,m!-00#!2+#,2#m7m.-0m#**-m1#m"#1!02Am#12#m%#,m#,m #*m ,9*'1'1m "#m m #,m *m .- *!'A,m Ym -0m #*m !-,200'-Zm #*m %#,m ;m 1'm 0#13*2Am ',2#0#1,2#m.0m#*m,9*'1'1m"#m!-m/3#m1#m.0#1#,209m.-12#0'-0+#,2#m m DMCMFTTTTTTTTTTT ,m *m ' *'-%0$>m 1#m #,!3#,20,m "'12',2-1m +-"-1m "#m #6.0#10m *m 21m "#m #$'!'#,!'m "#m +32!'A,m"#m3,m.- *!'A,m"#mYm*m!9*!3*-m 91'!+#,2#m"# #m2#,#0m#,m!3#,2m#*m ,B+#0-m"#m+.*'!-,#1m,*'8"-1Zm#*m,B+#0-m"#m$+'*'1mHm"#m*1m/3#m#129m!-+.3#12m *m.- *!'A,m7m#*m,B+#0-m"#m+32,2#1m#,!-,20"-1Ym,m*m *mIYGGm1#m.3#"#,m4#0m*1m 211m"#m+32!'A,m"#1!0'21m#,m"'4#011m.- *!'-,#1m"#mm.0m"'12',21m#1.#!'#1Ym 7m /3#m 2#,#0m #,m !3#,2m /3#m *m 21m - 2#,'"m ,-m 1#m &m !*!3*"-m "#m '%3*m +,#0m #,m !"m.- *!'A,Zm.-0m*-m/3#m!3*/3'#0m!-+.0!'A,m#1m.0-6'+2'4Ymm ,m #12#m 20 (-Zm #*m !9*!3*-m 1#m &m 0#*'8"-m 2#,'#,"-m #,m !3#,2m #*m ,B+#0-m "#m .0#1m "#m 1#1m,*'8"-1m#,mIm"#m*-1m%#,#1m/3#m1#m&,m#123"'"-m^Zm>m7mI#-)J>_Ym*m,-m .-"#0m,*'80m#*m%#,m;m#,m*m.- *!'A,m"#*mm1#m"#!'"'Am"#1!020m#12#m%#,m7m,-m 2#,#0*-m#,m!3#,2m.0m#*m!9*!3*-m"#m*m21m"#m+32!'A,Ym1>Zm#*m!9*!3*-m1#m&m&#!&-m"#*m 1'%3'#,2#m+-"-[m m Gj Em "#m 1#1m ,*'8"1m 6m Em "#m $+'*'1m /3#m 1#m &,m ,*'8"-m Sm Em 1#1m ,*'8"1m#,m2-2*m m Hj mEm 1#1m,*'8"1m#,m2-2*imEm"#m+32,2#1m#,!-,20"-1m#,m!"m.- *!'A,mSmmmm . im32,2#m T !+ TDMBBOT$'!'#,!'m"#m+32!'A,m"#m"'12',21m.- *!'-,#1m"#mm#,m"'12',21m#1.#!'#1Ym1m"-1mB*2'+1Zm 1-+ 0#"1Zm!-00#1.-,"#,mm*1m"#100-**"1m#,m+#*A,Ym m 1/$"($T %("($-"( T#$T ,32 "(>-T $%$0$-"( T # 0$'1&m GiHIK jGiKHMm m '#,&-*"1m7m!-*YZmHFFIm 0.#0m7m!-*YZmHFFJ\mm ,)-)*"#&O'&()!-.,O GiGKLm m ',)*#0m7m!-*YZmHFFKm ,#)*-#-O."&#(O GiIFFm m 0##,#m7m!-*YZmHFFIm O'3-O GiKFFm m '**m7m!-*YZmHFFJm GHKm .#9(OO'/.#)(-O Resultados ,34O-.#0O GiKFFm m 3m7m!-*YZmHFFKm ),/'O0/&!,O GiGFFFm m *"5#**m7m!-*YZmHFFJm ,#.#/'O-.#0/'OI@2JO GiHJm m *"#m7m!-*YZmHFFKm ,#.#/'O./,!#/'O-/-*EO /,/'OI>2JO GiJFm m *"#m7m!-*YZmHFFKm #!)O.,/(./&O GiJNKm m #m'%,-0m7m!-*YZmHFFOm GiKMIm m &+,'j0"1m7m!-*YZm HFGFm GiGYKm m-m FYIIiKFFm m -,8*#8j-m7m!-*YZmHFGGm $$P' 0$-2 (1QT PTQT $$P($+T#$T /.Q$"#$ m ,m*m.- *!'A,mm1#m&,m,*'8"-mIYNMGmm. m^GYGNNm#,mZmGYLLOm#,m>m7mGYFGJm#,m I#-)J>_m#,m3,m2-2*m"#mHYILNm$+'*'1Ym*m,B+#0-m2-2*m"#m. m,*'8"-1m#1m"#mOZGMm Ym #,'#,"-m #,m !3#,2m /3#m .0m *-1m 20#1m %#,#1m 1#m &,m #,!-,20"-m Lm +32,2#1Zm .-"#+-1m #6.0#10m*m21m"#m+32!'A,m!-+-m/3#m!"mGYKHNm m.-"0>+-1m#,!-,200m3,m+32,2#Ym m*-m/3#m#1m*-m+'1+-ZmFZIIm+32,2#1imKFFm m.0m.-"#0m!-+.00m+#(-0m!-,m*1m211m - 2#,'"1m#,m-201m.- *!'-,#1m"#m-201m#1.#!'#1m^ *mIYGG_Ym #m "#!'0m /3#m .0m /3#m 3,m 21m "#m +32!'A,m 1#m +91m $' *#m &!#m $*2m ,*'80m 3,m +7-0m,B+#0-m"#m%#,#1mm*-1m,*'8"-1m#,m#12#m20 (-Ym*m,B+#0-m"#m%#,#1m,*'8"-1m "30,2#m#*m"#100-**-m"#m-201m.- *!'-,#1m#1m%#,#0*+#,2#mGFm^3m7m!-*YZmHFFK\m*"5#**m 7m!-*YZmHFFJ\m0##,#m7m!-*YZmHFFI\m&+,'j0"1m7m!-*YZmHFGF_Ym 129m"#1!0'2-m/3#m.0m/3#m3,m.- *!'A,m"#mm1#mB2'*m13m21m"#m#$'!'#,!'m"# #m "#m 1#0m TGm +32,2#iKFFm m ^'**Zm HFFM_Ym ',m #+ 0%-Zm "# #+-1m 2#,#0m #,m !3#,2m /3#m #12m 21m "#m +32!'A,m 1#m &m !*!3*"-m #,m 00-8m 7m #,m 3,m .- *!'A,m "#m MLNm ',"'4'"3-1m ^'**Zm HFFM_Ymm m21m- 2#,'"m#,m*m.- *!'A,m"#*mZm201m,*'80mGGm%#,#1m&m1'"-m"#mGiKMIm m ^&+,'j0"1m 7m !-*YZm HFGF_Ym #0-m .0m .-"#0m #12 *#!#0m 3,m +#(-0m !-+.0!'A,m #,20#m *1m .- *!'-,#1m m #m Zm 1#m &m 2#,'"-m #,m !3#,2m .0m #12m B*2'+m 1A*-m #*m ,9*'1'1m !-,m *-1m %#,#1m /3#m 1#m &,m ,*'8"-m #,m + 1m .- *!'-,#1m ^>FO I#-)J>Zm _Ym,m4#8m0#*'8"-m#*m!9*!3*-m"#m*m21m"#m+32!'A,m"#m*m.- *!'A,mm!-,m*-1m !0'2#0'-1m "#1!0'2-1m ,2#0'-0+#,2#m 1#m &m - 2#,'"-m 3,m 21m "#m +32!'A,m "#m Gm +32!'A,m !"mKFFm Zmm.02'0m"#mGOm+32,2#1m#,mHYJNIm$+'*'1Ym m T T T T GHLm .#9(OO'/.#)(-O Resultados !+ TDMBCOT1m"#m+32!'A,m#,m*1m.- *!'-,#1m"#mm"#*mm7m#*mYm m T 32 -2$1T $-$1T - +(8 #.1T /!T - +(8 #.1T ,(+( 1T 1 T Lm Im INMHm HILNm GiGZK m GOm Im INMHm HJNIm GiKFF m .!+ "(>-T T .!+ "(>-T T m ',*+#,2#Zm2#,'#,"-m#,m!3#,2m*m#$'!'#,!'m0#/3#0'"m1#%B,m'**ZmHFFMm1#m&m!*!3*"-m#*m 0#,"'+'#,2-m"#m*m.- *!'A,[m m $'!'#,!'m0#*mmmmmm6mGFFmSmPm"#m0#,"'+'#,2-m#$'!'#,!'m#1.#0"m $'!'#,!'m2#A0'!m m -0m*-m2,2-m#,m*m.- *!'A,mm1#m&m- 2#,'"-m3,mIIPm^^GiGKFFm iGiKFFm _m6GFF_m"#m 0#,"'+'#,2-m "#m +32!'A,m +'#,201m /3#m #,m *m .- *!'A,m "#*m Zm 3,m GFFPm ^^GiKFFm iGiKFFm _m 6m GFF_Ym m #$'!'#,!'m "#m +32!'A,m #,m *m .- *!'A,m "#*m m &m 1'"-m !*0+#,2#m13.#0'-0m^20#1m4#!#1m+91Zm.0-6'+"+#,2#_mm*m#,!-,20"m#,m*m.- *!'A,m "#*mYmm m GHMm ) Resultados T DMDT".T m ,m#12#m20 (-m1#m&,m,*'8"-m+#"',2#m!-m*-1m%#,#1m>m7m;Ym-1m %#,#1mm7mI#-)J>m$3#0-,m,*'8"-1m#,m#*mZm#,m#*m+0!-m"#*m.0-7#!2-m Ym 1m GGIm 40'#""#1m "#m +#*A,m ,*'8"1m !-00#1.-,"#,m m .02#m "#m *m !-*#!!'A,m "#*m ,!-m "#m %#0+-.*1+m "#*m m 7m 0#.0#1#,2,m 3,m %0,m 40' '*'""m m ,'4#*m $#,-2>.'!-m 7m /3#m 1-,m -0'%',0'1m "#m IOm .>1#1m "'12',2-1m 7m .#02#,#!'#,2#1m m "'12',2-1m %03.-1Ym 91m !-,!0#2+#,2#m #,!-,20+-1m Gm 40'#""m .#02#,#!'#,2#m#*m%03.-m"3"'+ZmHLm+#*-ZmIm!-,-+-,ZmGHm!,2*3.#,1'1ZmJJm',-"-031Zm Mm $*#63-1-1Zm Hm +-+-0"'!Zm Gm "8&30j!&2#Zm GFm %0#12'1Zm Jm !&,"*)Zm Gm 22')m 7m Gm +#0'm ^,#6-m Y)_Ym #m &m - 1#04"-m /3#m #6'12#m 40' '*'""m ,230*m #,20#m *1m GGIm 40'#""#1m,*'8"1m7m*m*>,#m"#m0#$#0#,!'mLHjGGIm.0m#12-1m"-1m%#,#1Ym m DMDMBTTT".TTTT!T 0m#*m,9*'1'1m"#m!-m1#m31Am*m+'1+m#1202#%'m31"m.0m#*mm "#m+-"-m/3#m1#m,*'80-,m*-1m"-1m+.*'!-,#1m"#*m%#,m>m#,m*1mGGIm!!#1'-,#1Ym *m.0'+#0m+.*'!A,m',!*37#m#*m.0'+#0m#6A,m+'#,201m/3#m#,m#*m1#%3,"-m.0#1#,2m*-1m !320-m#6-,#1m0#12,2#1m/3#m!-,2'#,#m#*m%#,m>m^'%30mIYGJ_Ym*m'%3*m/3#m.0m#*m +<2-"-m"#mZm+#"',2#m*m1#!3#,!'!'A,m"#m*1m40'#""#1m^1#m#1!-('#0-,m"-1m 40'#""#1m.-0m!"mm4'13*'8"-m#,m#*m%#*_m.3"'+-1m"#2#0+',0m*m.-1'!'A,m"#m *-1m 1m 7Zm *m +'1+-m 2'#+.-Zm !-+.0- 0m 1'm <12-1m .0-4-! ,m !+ '-1m #,m *m 1#!3#,!'m+',-!>"'!Ymm ,m#*m.0'+#0m+.*'!A,m1#m"#2#!20-,mMm1m^GYGmmGYM_m^'%30mIYHNm7m *mIYGI_Zm"#m *-1m/3#m1A*-m#*mmGYKm.0-4-!m3,m!+ '-m"#m+',-9!'"-[m1.MG*7Ym*m.0-%0+m m 1'%,m 3,m 4*-0m "#m FYFFm m #12#m !+ '-m 7m .-0m *-m 2,2-Zm "#2#0+',m /3#m .3#"#m $#!20m m *m $3,!'-,*'""m "#m *m .0-2#>,Ym A*-m *m !!#1'A,m m KFKLFHm !-,2'#,#m #12#m Zm#,m&#2#0-!'%-1'1Ymm m GHNm ) Resultados m m !_m T (&30 T DMCIOT #*m "#m !-m .0m #*m .0'+#0m +.*'!A,m "#m >Ym _m !,*m MFFZm _m !,*m NFFYm "m!00'*m!-00#1.-,"#mm*m+#8!*m"#m3,m"#m*1mGGIm40'#""#1m!-,m*m0#$#0#,!'mLHjGGIYm,m0-(-m7m 4#0"#m 1#m &,m "#2**"-m *-1m &#2#0-"B.*#6m "#2#!2"-1m ^GYGjGYM_Ym ,m +0'**-m 1#m "#2**,m *%3,-1m &#2#0-"B.*#6m $*1-1m -m 02#$!2-1m "#1!02"-1m +#"',2#m 1#!3#,!'!'A,Ym *%3,-1m &#2#0-"B.*#6m ,-m 1#m 4'13*'80-,m !-00#!2+#,2#m #,m + -1m !,*#1m 1',-m 1A*-m #,m 3,-m "#m #**-1Zm !_m *-!*'8!'A,m "#m *-1m 1m "#2#!2"-1m+#"',2#m!-m#,m#*m.0'+#0m+.*'!A,Ym m GHOm ) Resultados *m 0#12-m "#m 1m "#2#!2"-1m #,m #*m .0'+#0m +.*'!A,m "#m >m 1-,m 1'*#,!'-1-1m -m ,-m #129,m #,m 0#%'A,m #6A,'!Ym *m m GYLm ^'%30m IYHO_m #1m 3,m .-*'+-0$'1+-m !-+.*#(-Zm $-0+"-m .-0m 3,m ',1#0!'A,m "#m "-1m 2'+',1m 7m 3,m +'!0-12<*'2#Ym -0m *-m 2,2-Zm #*m &#2#0-"B.*#6m $-0+"-m #,m #12#m !1-m .3#"#m 1#0m "# '"-m m *m ',1#0!'A,m "#m *1m "-1m 2'+',1m-m*m+'!0-12<*'2#m/3#m#129m*-!*'8"-m(312-mm!-,2',3!'A,Ym,m*m'%30mIYHOm .3#"#m 4#01#m !-+-m 3,m "#m *1m 40'#""#1m /3#m !-,2'#,#,m #12#m .-*'+-0$'1+-m ^JMJ_m !-,2'#,#m *1m ',1#0!'A,m "#m "-1m 2'+',1m 1#%3'"1m "#*m +'!0-12<*'2#m ^_MZm +'#,201m /3#m *m 40'#""m "#m 0#$#0#,!'m LHjGGIm ,-m !-,2'#,#m *m ',1#0!'A,m 7m #*m ,B+#0-m"#m0#.#2'!'-,#1m"#*m+'!0-12<*'2#m#1m^_LYmm m (&30 TDMCJOT0-+2-%0+m"#m*1m40'#""#1mJMJm7mLHjGGIm#,m*m0#%'A,m/3#m!-,2'#,#m#*mmGYLmYm *mmGYLm#129m!-+.3#12-m.-0m3,m',1#0!'A,m"#m"-1m2'+',1m7m3,m0#.#2'!'A,m"'!'-,*mm#,mJMJYm m m GIFm m ) Resultados !+ TDMBDOT-1'!'A,Zm!+ '-m"#m,3!*#A2'"-m7m"#m+',-9!'"-m"#m!"mm"#2#!2"-Zm40'#""#1m/3#m*-m !-,2'#,#,m7m#*m2+@-m"#*m$0%+#,2-m"#m"'%#12'A,m1#%B,mMFFm7mNFFm.0m#*m.0'+#0m+.*'!A,m"#*m %#,m >Ym ,m 1-+ 0#"-m %0'1Zm #*m m GYKm /3#m .0-4-!m 3,m !+ '-m ,-m 1',A,'+-m #,m *m .-1'!'A,m MGm "#m *m 1#!3#,!'m.0-2#'!Ymg[m'#*m"#m.-Zm![m!!#1'A,Ym m m GYGm -1'!'A,m Kdm m ^j!_gm ^jJH_m m jm m jm -+ 0#m0'#""#1m mKFKLFHZmmHNHJJNm mHLLOJMZmmGHJGGHm +@-m +@-m $0%+#,2-m $0%+#,2-m !,*mm !,*mm mMFFm mNFFm KFm. m JKFm. m GMHm. m IHNm. m HGJm. m HNLm. m HMMm. m HHIm. m DADT/!T BJHT/!T IIJm. m GLLm. m JGOm. m NGm. m HFLZmGONm GYHm 6A,Gm NGm 0%HM0%m jm mJILKIJZmmGHJGGHm mHLLOJMZmmHNHJJNm mLGNNKJZmjjGFm GYIm 6A,Gm GHIm *JG*m jm mGNKGGGZmmmmJILKIJm mHNMm HOJZmHKOm mGJFLIHZmILIm HHKZmIMHm mJILKIJZmjHNMm GYJm 6A,Gm GNLm #3KK#3m jm mGNKGGGZmmGLJIHFm jjHZmjjGFOm jKKFZmjLHm JGLZmJLNm JMJZmKFFm ,1GIFFIHZmmHNHJJNm BMFT 6>-BT CBCT 1/HB+7T AMAAT TFAFGACT HOJZmHKOm mGJFLIHZmHHKm m^_mMm GYLm ,20A,mGm HJIm &0NG&0m ST jj^_mLm mHNHJJNZmIJJm KIZmjjHm jKKFZmjLHm JGLZmJMJm GYMm ,20A,mGm IHNm jm ST mGJFLIHZmjjHm jjNZmJMJm m GIGm Resultados ) 0m#*m1#%3,"-m+.*'!A,m1#m"#2#!20-,mKm1m^'%30mIYIFZm *mIYGJ_m.#0-m1A*-m #*mmHYKm#129m*-!*'8"-m#,m0#%'A,m#6A,'!Ym',m#+ 0%-Zm#*m!+ '-m"#m+',-9!'"-m /3#m.0-4-!m#1m1',A,'+-m^71HIF71_m7m.-0m*-m2,2-m,-m$#!20>mm*m$3,!'-,*'""m "#m *m .0-2#>,Ym ,m *m '%30m IYIFm .3#"#m 4#01#m #*m %#*m !-,m *-1m &#2#0-"B.*#6m '"#,2'$'!"-1m.0m#12#m+.*'!A,Ym#1"#m#*m.3,2-m"#m4'12m$#,-2>.'!-m*-1m&.*-2'.-1m "#2#!2"-1m #,m #12#m 1#%3,"-m +.*'!A,m ,-m 2'#,#,m ,',%B,m ',2#0<1m 7m /3#Zm -m #129,m *-!*'8"-1m#,m0#%'A,m',20A,'!Zm-m.0-4-!,m!+ '-1m1',A,'+-1Ym 1#04,"-m *1m "'12',21m !-+ ',!'-,#1m #,20#m *-1m 1m '"#,2'$'!"-1m #,m *1m GGIm !!#1'-,#1m1#m&,m1'%,"-m3,m2-2*m"#mGOm&.*-2'.-1Ym#m*1mGGIm!!#1'-,#1ZmLNm,-m .0#1#,2,m ,',%B,m .-*'+-0$'1+-m 0#1.#!2-m *m 40'#""m "#m 0#$#0#,!'m 7m .-0m *-m 2,2-m 2'#,#,m#*m+'1+-m%#,-2'.-m#,m*-1m$0%+#,2-1m,*'8"-1m"#*m%#,m>O1'%,9,"-*#1m 1>m #*m &.*-2'.-m !#0-m ^F_Ym ,m !+ '-Zm *1m JKm !!#1'-,#1m 0#12,2#1m .0#1#,2,m 1m /3#m*1m"'$#0#,!',m"#m*m40'#""mLHjGGIYm ,m *m *m IYGKm 1#m .0#1#,2,m *-1m .-*'+-0$'1+-1m /3#m .0#1#,2m !"m !!#1'A,Zm *1m !3*#1m &,m 1'"-m -0"#,"1m 1#%B,m *m !,2'""m "#m 1m /3#m !-,2'#,#,Zm #+.#8,"-m .-0m *1m /3#m !-,2'#,#,m 1A*-m 3,m m 7m !-,2',3,"-m .-0m *1m /3#m !-,2'#,#,m !-+ ',!'-,#1m"#m"-1Zm20#1Zm!320-Zm1#'1m7m1'#2#m1Ym 1#04,"-m *m *m IYGKm 1#m .3#"#m $'0+0m /3#m *-1m 1m /3#m .0#!#,m !-,m +91m $0#!3#,!'m1-,m#*mmGYJm.0m#*m.0'+#0m+.*'!A,m7m#*mmHYGm.0m#*m1#%3,"-Zm/3#m .0#!#,m #,m HFiGGIm 7m GLiGGIm !!#1'-,#1Zm 0#1.#!2'4+#,2#Ym m *m ',4#01Zm *-1m +#,-1m $0#!3#,2#1m7m.-0m*-m2,2-m*-1m+91m#1.#!>$'!-1m"#m!!#1'A,m1-,m*-1m1mGYGZmGYIZmGYKm7m #*m m GYMm .0m #*m .0'+#0m +.*'!A,Zm .0#!'#,"-m #,m 2,m 1A*-m JiGGIZm IiGGIZm GiGGIm 7m JiGGIm!!#1'-,#1Zm0#1.#!2'4+#,2#Ym0m#*m1#%3,"-m+.*'!A,m#*mmHYKm#1m#*m+#,-1m $0#!3#,2#m.0#!'#,"-mB,'!+#,2#m#,m*m!!#1'A,mmKFKLFHZm/3#m2+ '<,m#1m*mB,'!m /3#m!-,2'#,#m#*mmGYKYmm ,m 2-2*Zm 1#m &,m "#2#!2"-m GHm .-*'+-0$'1+-1m 0#1.#!2-m m *m 40'#""m LHjGGIm #,m JKm !!#1'-,#1m"#m*1mGGIm,*'8"1Zm#,m3,m0#%'A,m"#mGLLOm. m^KFFQGGLOm. _Ymm *m&.*-2'.-m+91m$0#!3#,2#m#1m#*mKm^mHYG_Zm#,!-,20"-m#,mGFm!!#1'-,#1Zm1#%3'"-m "#*m Hm ^m GYJ_m #,!-,20"-m #,m Mm !!#1'-,#1Ym 6'12#,m GGm &.*-2'.-1m /3#m 1#m #,!3#,20,m1A*-m#,m3,m!!#1'A,m^JZmMZmNZmGFZmGGZmGIZmGJZmGKZmGLZmGMm7m GN_Ym*m+91m0#*#4,2#m#1m#*mGIZm7m/3#m#1m#*mB,'!-m/3#m!-,2'#,#m*-1m1mGYKm7mHYKm ^ *m IYGK_Zm 1'#,"-m #*m GYKm ^'%30m IYIG_m #*m B,'!-m /3#m .0-"3!#m 3,m !+ '-m "#m +',-9!'"-m 7m 2'#,#m 3,m 4*-0m FYFFm #,m Ym m !!#1'A,m /3#m *-m !-,2'#,#m #1m *m m KFKLFHZm .#02#,#!'#,2#m *m %03.-m %0#12'1m 7m .0-4#,'#,2#m "#m + 'Ym ',m #+ 0%-Zm m GIHm ) Resultados #12#m!+ '-m"#m+',-9!'"-m,-m1#m*#m.3#"#m20' 3'0m3,m$#,-2'.-m!-,!0#2-m0#*!'-,"-m !-,m0#1'12#,!'m.3#12-m/3#m,-m&7m',$-0+!'A,m ' *'-%09$'!m,'m#6.#0'+#,2*m!-,m*m /3#m1#m.3#"m0#*!'-,0m#12#m%#,-2'.-m!-,m3,m0#1'12#,!'m$0#,2#m*%B,m4'031Ymm m m m !_m m m (&30 TDMDAOT#*m"#m!-m.0m#*m1#%3,"-m+.*'!A,m"#m>Ym_m!,*mMFFm _m!,*mNFFYm "m!00'*m!-00#1.-,"#mm*m+#8!*m"#m3,m"#m*1mGGIm40'#""#1m!-,m*m0#$#0#,!'mLHjGGIYm,m0-(-m7m 4#0"#m 1#m &,m "#2**"-m *-1m &#2#0-"B.*#6m "#2#!2"-1m ^m HYGjHYK_Ym ,m +0'**-m 1#m "#2**,m *%3,-1m GIIm ) Resultados &#2#0-"B.*#6m $*1-1m -m 02#$!2-1m "#1!02"-1m +#"',2#m 1#!3#,!'!'A,Zm !_m *-!*'8!'A,m "#m *-1m 1m "#2#!2"-1m+#"',2#m!-m#,m#*m1#%3,"-m+.*'!A,Ym m !+ TDMBEOT-1'!'A,Zm!+ '-m"#m,3!*#A2'"-m7m"#m+',-9!'"-m"#m!"mm"#2#!2"-Zm40'#""#1m/3#m*-m !-,2'#,#,m7m#*m2+@-m"#*m$0%+#,2-m"#m"'%#12'A,m1#%B,mMFFm7mNFFm.0m#*m1#%3,"-m+.*'!A,m"#*m %#,m>Emg[m'#*m"#m.-Zm![m!!#1'A,Ym m m -1'!'A,m ^j!_gm m m -+ 0#m0'#""#1m +@-m +@-m $0%+#,2-m $0%+#,2-m !,*mm !,*mm mMFFm mNFFm ILGm. m NFNm. m KOGm. m KMNm. m MOIm. m IMLm. m NHJm. m IJKm. m NLJm. m IFKm. m JINZmmGJFLIHm mJOFINNZmILIm IINZmmHNHJJNm HYGm ,20A,Hm HHNKiQm jm jm mHLLOJMZmmGHJGGHm jjOZmmGLOIHOm mGLOILNZmjHJGm YmNHGKZmKFFm 1'!jLZm7HNKm JINZmGONm HYHm ,20A,Im HKGKm jm jm mHNHJJNZmHNMm mHLLOJMZmmGHJGGHm mJOFINNZmmHMLLLFm HYIm ,20A,mJm HMGMm jm jm mHLLOJMZmmGHJGGHm GONZmmGLMFKMm mHNHJJNZmmHLLOJMm HYJm ,20A,Jm HMJNm jm jm mGHJGGHZmGONm JINm HYKm T m m m m m m GIJm 6A,Km HMNNm 71HIF71m jm mKFKLFHm ) Resultados !+ T DMBFOT .*-2'.-1m #,!-,20"-1m +#"',2#m #*m ,9*'1'1m .-0m !-m "#m *-1m "-1m +.*'!-,#1m "#m #JYm ,m 1-+ 0#"-m %0'1m 1#m &m "#2**"-m #*m m GYKm /3#m .0-4-!m 3,m !+ '-m "#m +',-9!'"-m #,m *m !!#1'A,mKFKLFHYmm Tm -+ 0#m GYGm GYHm GYIm GYJm BMFT GYLm GYMm HYGm HYHm HYIm HYJm HYKm HFLm m 6m m m T m m m m m m m mLGNNKJm m 6m m m T m m m m m m m jjGFm m 6m m m T m m m m m m m ILIm m m m 6m T m m m m m m m HHKm m m m 6m T m m m m m m m IMHm m m m 6m T m m m m m m m mGLJIHFm m m m 6m T m m m m m m m 40'#""m jjGFOm m m m 6m T m m m m m m m JLNm m m m 6m T m m m m m m m 1GIFFIHm m m m 6m T m m m m m m m HHKm m m m m T 6m m m m m m m IJJm m m m m T 6m m m m m m m KIm m m m m T 6m m m m m m m jNm m m m m T m 6m m m m m m mGJFLIHm m m m m T m m 6m m m m m ILIm m m m m T m m 6m m m m m IINm m m m m T m m 6m m m m m jjOm m m m m T m m 6m m m m m mGLOIHOm m m m m T m m 6m m m m m mGLOILNm m m m m T m m 6m m m m m .*-2'.-[m1m G[GYHm H[mGYJm I[mGYLm J[GYMm K[mHYGm jHJGm m m m m T m m 6m m m m m YmNHGKm m m m m T m m 6m m m m m 1'!jLm m m m m T m m 6m m m m m HNKm m m m m T m m 6m m m m m mJOFINNm m m m m T m m m 6m m m m mHMLLLFm m m m m T m m m 6m m m m mGLMFKMm m m m m T m m m m 6m m m M[HYIm mGNKGGGm m m 6m 6m T m m m m m m m N[mGYIQGYJm HOJm m m m 6m T 6m m m m m m m HKOm m m m 6m T 6m m m m m m m jKKFm m m m 6m T 6m m m m m m m L[HYHm O[mGYJQGYLm GIKm ) Resultados jLHm m m m 6m T 6m m m m m m m JGLm m m m 6m T 6m m m m m m m KFFm m m m 6m T m m 6m m m m m GF[mGYJQHYGm mJILKIJm m 6m 6m 6m T m m m m m m m GG[mGYHQGYIQGYJm jjHm m m m 6m T 6m 6m m m m m m JMJT m m m 6m T 6m 6m m m m m m TFAFGACm 6m m m m 6T m m m m m m 6m BDOBMBLBMFLCMFT HNMT m m 6m 6m T m m m 6m m m m GJ[mGYIQGYJQHYHT JINm m m m m T m m 6m 6m m 6m m GK[mHYGQHYHQHYJT GONm m 6m m m T m m m 6m 6m 6m m mGJFLIHm m m m 6m T 6m 6m 6m m m m m mHLLOJMm 6m 6m m m T m m 6m 6m 6m 6m m mGHJGGHm 6m 6m m m T m m 6m 6m 6m 6m m mHNHJJNm 6m 6m m 6m T 6m m 6m 6m m 6m m GH[mGYJQGYLQGYMm GL[m GYHQHYHQHYIQHYJm GM[m GYJQGYLQGYMQHYGm GO[m GYGQGYHQHYGQHYHQHYI QHYJm GN[GYGQGYHQGYJQGY LQHYGQHYHQHYJm m m m (&30 TDMDB[m0-+2-%0+1m"#m*m40'#""m"#m0#$#0#,!'mLHjGGIm7m*m!!#1'A,mmKFKLFHZm/3#m!-,2'#,#m #*mmGYKm0#1.-,1 *#m"#m3,m!+ '-m"#m+',-9!'"-m^9!'"-m1.902'!-mm%*'!',_Ym T DMDMCTTT".TTTT T *m+.*'!A,m0120#"-m+#"',2#m!-m!-00#1.-,"#m*m.0'+#0m#6A,m"#m;Zm "#mLGKm .m^'%30mIYHL_Ym#m&,m"#2#!2"-m"-1m.-*'+-0$'1+-1m#,20#m*m40'#""mLHj GGIm7m*1mGGIm!!#1'-,#1m,*'8"1Ym,m*m'%30mIYIHm1#m.3#"#m- 1#040m#*m%#*m!-,m*m .-1'!'A,m "#m *-1m "-1m 1m "#2#!2"-1Ym 0m !"m %#,m ,*'8"-m +#"',2#m GILm ) Resultados !-m234'#0-,m/3#m0#*'801#m"-1m%#*#1m""-m/3#m#*m,B+#0-m"#m40'#""#1mm ,*'80m #0m 13.#0'-0m *m +B+#0-m "#m +3#1201m /3#m .3#"#,m !0%01#m #,m 3,m %#*m "#m Ym 12#m #1m #*m +-2'4-m .-0m #*m !39*m #,m *m '%30m IYIHm ,-m #129,m 0#.0#1#,2"1m 2-"1m*1m40'#""#1m7m.-0m*-m2,2-m,-m#129,m"#2**"-1m2-"-1m*-1m&#2#0-"B.*#6Ym m m m !_m m (&30 TDMDCOT#*m"#m!-m.0m#*m+.*'!A,m"#*m%#,m;Ym_m!,*mMFFZm _m!,*mNFFYm"m !00'*m!-00#1.-,"#mm*m+#8!*m"#m3,m"#m*1mGGIm40'#""#1m^3,/3#m#,m!"m%#*m1A*-m1#m!0% ,mOLiGGI_m !-,m*m0#$#0#,!'mLHjGGIYm,m0-(-m7m4#0"#m1#m&,m"#2**"-m*-1m&#2#0-"B.*#6m"#2#!2"-1m^mGm7mH_Ym,m +0'**-m 1#m "#2**,m *%3,-1m &#2#0-"B.*#6m $*1-1m -m 02#$!2-1m "#1!02"-1m +#"',2#m 1#!3#,!'!'A,Zm !_m *-!*'8!'A,m"#m*-1m1m"#2#!2"-1m+#"',2#m!-m#,m#*m.0'+#0m#6A,m"#*m%#,mGYm T GIMm ) Resultados *m m Gm ^ *m IYGLZm '%30m IYII_m .0-4-!m 3,m !+ '-m "#m +',-9!'"-m "#m *#3!',m m 4*',m 3,/3#m 1#%B,m *-1m 4*-0#1m - 2#,'"-1m +#"',2#m m ^4*-0m GYFF_m #1m .-!-m .0- *#m/3#m$#!2#mm*m$3,!'-,*'""m"#m*m.0-2#>,Ym1m40'#""#1m/3#m!-,2'#,#,m #*mmGm1-,mmGHJGGHZmmJNHJHOZmIJOZmmJILKIJm7mmHNHJJNYmm m m (&30 T DMDDOT 0-+2-%0+m "#*m m Gm "#*m .0'+#0m #6A,m "#*m %#,m ;Zm /3#m .0-4-!m 3,m !+ '-m "#m +',-9!'"-m"#m*#3!',mm4*',m#,m*m40'#""mmHNHJJNYm m -"1m#121m40'#""#1m.#02#,#!#,mm%3.-1m"'12',2-1m^+-+-0"'!Zm%0#12'1Zm+#*-m7m $*#63-131_m7m1-,m"#m-0>%#,#1m%#-%09$'!-1m"'12',2-1m^,"'Zm'+ 5#Zm0)Zm#,#%*m7m 3"9$0'!_Ym *m m Hm ,-m .0-4-!m ,',%B,m !+ '-m "#m +',-9!'"-Ym #m .3#"#m "#12!0m /3#m <12#m .0-4-!m 3,m !+ '-m #,m *m 40'#""m m GHJGGHm "#m LOIm 7Zm 1',m #+ 0%-Zm #,m *1m 40'#""#1mmHNHJJNm7mmJNHJHOm#*m!+ '-m#1m"#mLOIYmm #"',2#m *m !-+ ',!'A,m "#m *-1m "-1m 1m 1#m &,m '"#,2'$'!"-m "-1m &.*-2'.-1m "'12',2-1m ^ *m IYGM_Ym #%B,m *-1m 0#13*2"-1m - 2#,'"-1m 1#m .3#"#m - 1#040m !-+-m #*m .0'+#0m#6A,m"#*m%#,m;m.0#1#,2m.-!m40' '*'""m.3#12-m/3#m1A*-mKm!!#1'-,#1m "#m *1m GGIm ,*'8"1m "'$'#0#,m #,m *%3,-m "#m *-1m "-1m .-*'+-0$'1+-1m 0#1.#!2-m m *m 40'#""m#129,"0Ymm T !+ TDMBGOm -*'+-0$'1+-1m "#2#!2"-1m #,m #*m .0'+#0m #6A,m "#*m %#,m;m #,20#m *m 40'#""m LHjGGIm 7m *1m m -1'!'A,m m ^j!_gm m m Gm 6A,Gm LMFm #3HHJ*m GYFFm Hm 6A,Gm LOIm LOIm 0-HIG0-m jm GINm -+ 0#m0'#""m mGHJGGHZmmJNHJHOm IJOZmmJILKIJm mHNHJJNm mGHJGGHm^_ZmmHNHJJNm^_m mJNHJHOm^_m m +@-m +@-m $0%+#,2-m $0%+#,2-m !,*m !,*m mMFFm mNFFm IMNm. m HMHm. m JFGm. m m HJOm. m m ) Resultados GGIm!!#1'-,#1m,*'8"1Ym#m',!*37#,m2+ '<,m*-1m"2-1m"#m*1m40'#""#1m/3#m!-,2'#,#,m!"mm1>m !-+-m#*m2+@-m"#*m$0%+#,2-m"#m"'%#12'A,m4'13*'8"-m#,m+ -1m!,*#1m^MFFm7mNFF_Ymg[m'#*m "#m.-Zm![m!!#1'A,Ym T !+ TDMBHOT *m!-,m*-1m&.*-2'.-1m"#2#!2"-1m.0m#*m%#,m;Ym,m1-+ 0#"-m%0'1m1#m"#2**m#*mmGm /3#m.0-4-!m3,m!+ '-m"#m+',-9!'"-m^*#3!',mm4*',_m#,m*m.-1'!'A,mHHJm"#m*m1#!3#,!'m.0-2#'!Ym m -+ 0#m40'#""m BT Hm m IJOm 6T m T mJILKIJm 6T m mGHJGGHm 6T 6m mJNHJHOm 6T 6m mHNHJJNm 6T 6m m .*-2'.-im G[mGm H[GQHm GIOm Resultados .5&)!)OO'/.(.-O ().7*#)-OO m m DMETTTT$ T 30,2#m#*m1#%3,"-m@-m"#m2#1'1Zm1#m- 234'#0-,m*1m1#+'**1mHm"#m*1m$+'*'1m/3#m 0#.0#1#,20>,m *m .- *!'A,m "#m Ym -,(3,2+#,2#m !-,m *m #+.0#1m '#&&-O #.9m 1#m "#!'"'Am - 1#040m *m .- *!'A,m Hm m ,'4#*m $#,-2>.'!-Ym 1m .- *!'-,#1m "#m m1#m!0#,m+7-0+#,2#m.0m.*'!!'-,#1m"#m%#,<2'!m',4#01Ym1>Zm1#m','!'m *m "#2#!!'A,m "#m +32,2#1m #,m 3,m %#,m "#m ',2#0<1m 7m .-12#0'-0+#,2#m 1#m ,*'8m 1'm #*m %#,-2'.-m"#2#!2"-m#1m#*m0#1.-,1 *#m"#m3,m$#,-2'.-m- 1#04"-Ym#0-m2+ '<,m#6'12#m *m .-1' '*'""m "#m #4*30m $#,-2>.'!+#,2#m 2-"m *m .- *!'A,Zm -m .02#m "#m #**Zm .0m "#2#!20m $#,-2'.-1m ',2#0#1,2#1m 7m .-12#0'-0+#,2#m !0!2#0'80*-1m !-,m $',#1m !-+#0!'*#1m -m .-0m 13m ',2#0<1m '-*A%'!-Zm m .#10m "#m ,-m !-,-!#0m *m +32!'A,m 0#1.-,1 *#m"#m"'!&-m$#,-2'.-Ymm *m+<2-"-mA.2'+-m#1m"#100-**0m3,m 1#m"#m"2-1m"-,"#m*+!#,0m*-1m$#,-2'.-1m - 1#04"-1m "#m 3,m +-"-m -0"#,"-m .0m .-"#0m &!#0m B1/3#"1m #6&312'41m #,m $3,!'A,m"#m*m+-0$-*-%>m-m#*m2'.-m"#m#$#!2-m/3#m.0-"3!#m*m+32!'A,m"#1!-,-!'"Ym 20-m +-"-m "#m 310m *-1m "2-1m $#,-2>.'!-1m #1m #* -0,"-m 3,m .9%',m 5# m "A,"#m #*m 3130'-m .3#"m #*#%'0m 3,m +32,2#m $#,-2>.'!-m /3#m *#m ',2#0#1#Ym ,m 3#,m #(#+.*-m #1m " m &22.[ii30%4Y#407Y',0Y$0i" m "-,"#m 1#m .3#"#,m 1-*'!'20m 1#+'**1m +32,2#1m"#m%3'1,2#m^#-/'O-.#0/'m_m7m"#m2-+2#m^)&(/'O&3)*,-#/'_Ym#m.3#"#m #1!-%#0m #*m +32,2#m #,m $3,!'A,m B,'!+#,2#m "#m 3,m $#,-2'.-m ,-0+*+#,2#m +-0$-*A%'!-Zm#,m3,m%#,m"#m',2#0<1Zm-m&!'#,"-m&-.m!-,m#*m$0%+#,2-m"#m1#!3#,!'m /3#m,-1m.3#"m',2#0#10m#,m*m 1#m"#m"2-1Ym,m#12#m20 (-m,-m1#m&m#* -0"-m3,m 1#m "#m "2-1m .#0-m 1'm 3,m !29*-%-m $#,-2>.'!-m #,m $3,!'A,m "#m *1m "'12',21m #2.1m "#m !0#!'+'#,2-m "#m *m .*,2Ym 0m *-1m $#,-2'.-1m '"#,2'$'!"-1Zm 1#m &m &#!&-m 3,m "#1!0'.!'A,m"#m*m+32!'A,m!-,(3,2+#,2#m!-,m*m'"#,2'$'!!'A,m"#m*m$+'*'m/3#m*m !-,2'#,#m7m*m'+%#,m"#*m$#,-2'.-Ym 0m *m #+.0#1m '#&&-O #.9Zm *m .02#m +91m ',2#0#1,2#m 1#m !#,20 m #,m *1m !0!2#0>12'!1m "#*m $032-m 7m #,m 2020m "#m #,!-,200m $#,-2'.-1m ',2#0#1,2#1m m ,'4#*m !-+#0!'*Ym0m#**-Zm#,m#*m@-mHFFMm1#m.*,20-,mJFFm$+'*'1mHZm!-,!0#2+#,2#mGFm ',"'4'"3-1m .0m !"m $+'*'m ^3,m 2-2*m "#m JFFFm .*,21m .0-6'+"+#,2#_Ym *,2,"-m"'#8m',"'4'"3-1m.-0m$+'*'m1#m.0#2#,">m.-"#0m"'$#0#,!'0m*-1m$#,-2'.-1m "# '"-1m m #$#!2-1m + '#,2*#1Zm "#m *-1m #$#!2-1m .0-"3!'"-1m .-0m *%3,m +32!'A,m GJFm Resultados O .5&)!)OO'/.(.-O ().7*#)-O ',"3!'"m .-0m Ym + '<,Zm #,m 2-"-1m *-1m #12"'-1m #1234'#0-,m .0#1#,2#1m .*,21m !-,20-*m ^.*,21m "#m *m 40'#""m LHjGGI_m .0m .-"#0m !-+.00m 1'm #*m $#,-2'.-m - 1#04"-m#0m"# '"-mm3,m+32!'A,m-m*m+ '#,2#mm #1"#m*m%#0+',!'A,m"#m*1m1#+'**1mHm1#m&'8-m3,m1#%3'+'#,2-m#6&312'4-m"#m*1m .*,21m - 1#04,"-m 1'm .0#!>,m $#,-2'.-1m +32,2#1Ym ,m $3,!'A,m "#*m #12"'-m "#m *m .*,2m 1#m - 1#040-,m "'12',2-1m !0!2#0#1m ^.*9,23*Zm .*,2m "3*2m 7m $032-_Ym # #m "4#02'01#m/3#m#,m*%3,1m"#m*1m$+'*'1m.0#1#,2"1m#,m#*m!29*-%-Zm1A*-m3,-m"#m*-1m "'#8m',"'4'"3-1m.0#1#,2 m#*m$#,-2'.-m+32,2#Ym,m#12-1m!1-1m"# #0>,m.*,201#m +91m ',"'4'"3-1m Hm .0m .-"#0m 1#%300m /3#m #*m #$#!2-m $#,-2>.'!-m - 1#04"-m $3#m .0-4-!"-m .-0m 3,m +32!'A,m 7m ,-m !-+-m !-,1#!3#,!'m "#m *1m !-,"'!'-,#1m + '#,2*#1Ym*m20 (-m"#m!0#!'+'#,2-m7m+,2#,'+'#,2-m"#m*1m.*,21m$3#m0#*'8"-m .-0m*m#+.0#1m'#&&-O#.9Ymm T DMEMBTTTTTT m ,'4#*m "#m .*9,23*m 7m ,2#1m "#m 201.*,20m *m ',4#0,"#0-m 1#m &'8-m 3,m 1#%3'+'#,2-m "#2**"-m "#m !0!2#0>12'!1m 2*#1m !-+-m #*m ,B+#0-m "#m 1#+'**1m %#0+',"1m .-0m $+'*'m7m#*m,B+#0-m"#m.*,21m4' *#1m.-0m$+'*'Ym-,2 '*'8,"-m#12-1m0#13*2"-1m 1#m- 234'#0-,m*-1m.-0!#,2(#1m.0#1#,2"-1m#,m*m *mIYGNYmm m !+ TDMBIOT-0!#,2(#1m"#T%#0+',!'A,m#,m*1mJFFm$+'*'1mHm- 1#04"1Ym m +'*'1m,-m%#0+',"1m GZHKPm +'*'1m!-,m (m%#0+',!'A,m +'*'1m%#0+',"1m.#0-m!-,m ^+#,-1m"#mJjLmiGF_m *#2*'""m GGZNFPm IZHKPm mm #m- 1#040-,m40'-1m$#,-2'.-1m,-0+*#1m#,m*-1m/3#m*1m.*9,23*1Zm1',m**#%0mm1#0m "3*21Zm .0#1#,2 ,m +*$-0+!'-,#1Zm "#100-**-m ,-0+*m #,m #*m !0#!'+'#,2-Zm !*-0-1'1m3m-20-1m2'.-1m"#m*2#0!'-,#1m/3#m1#m.3#"#,m4#0m"#2**"1m#,m*m *mIYGOm7m #,m*1m'+9%#,#1m!-00#1.-,"'#,2#1m^IYJYJm29*-%-m"#m'+9%#,#1_Ym m m m m m m GJGm .5&)!)OO'/.(.-O ().7*#)-OO Resultados !+ T DMBJT #,-2'.-1m #,!-,20"-1m #,m #12"'-m "#m .*9,23*Yg29*-%-m "#m '+9%#,#1m IYJYJYm ggm *%3,1m .*,21m &,m +-120"-m #*m $#,-2'.-m +32,2#m #,m "'$#0#,2#1m #12"'-1m "#m !0#!'+'#,2-Zm .-0m *-m 2,2-Zm *1m #,!-,200#+-1m2,2-m#,m#*m!29*-%-m0#*'8"-m.0m#*m#12"'-m"#m.*9,23*m!-+-m#,m#*m"#m.*,2m"3*2Ym m *,21m!-,m #,-2'.-m +'*'m $#,-2'.-m +%#,gm +32,2#i+'*'m 04'20-.'1+-Ym #100-**-m ,-0+*m ,!&1m !*-0A2'!1Ym *-0-1'1m.0!'*m HHm IiGFm Gm KKm KiGFm Hm MONm GiGFm Mm GIHLm KiOm GFm GKFKm GiHm GGm GKHKm HiOm GHm GLJLm IiGFm GJm GMOFm NiOm GKm GNMLm IiMm GLm GOFHm GiNm Om HGOIm GiOm GNm HIGKm JiLm GOm KKm KiGFm Hm KNggm HiGFm Im NGm MiOm Km GIMm MiGFm Lm MONm GiGFm Mm OMOm JiGFm Nm GKHKm HiOm GHm GKKFm GiHm GIm GIHLm KiOm GFm GOFHm GiNm Om GOIJm KiLm GMm HIGKm JiLm GOm "&#1'A,m"#m*1m MJm LiGFm Jm .0'+#01m&-(1m NGm MiGFm Km m T DMEMCTTTTTTT ,m #*m #12"'-m "#m .*,2m "3*2m 1#m - 1#040-,m !+ '-1m #,m #*m "#100-**-Zm 1>m !-+-m !+ '-1m#,m*m.'%+#,2!'A,Zm!+ '-1m#,m*m$-0+m"#m*m&-(m-m#,m*m$*-0Zm#,,'1+-Zm7m -20-1m $#,-2'.-1m ^ *m IYHF_Ym -+-m #*m !0' "-m #0m *#2-0'-m ,-m #1.#09 +-1m 3,m GJHm Resultados O .5&)!)OO'/.(.-O ().7*#)-O $#,-2'.-m !-,!0#2-Zm 1',-m "#1!3 0'0m ,3#4-1m $#,-2'.-1Zm /3'891m ,-m - 1#04"-1m ,2#0'-0+#,2#m#,m*m#1.#!'#Ym m !+ TDMCAT#,-2'.-1m#,!-,20"-1m#,m#12"'-m"#m.*,2m"3*2Ymg29*-%-m"#m'+9%#,#1mIYJYJYm m #,-2'.-m +'*'m 04'20-.'1+-Ym #100-**-m,-0+*m *,21m!-,m$#,-2'.-m +32,2#i+'*'m +%#,gm ONKm KiGFm HGm GFNLm GiOm HHm HHLGm HiOm HNm HHNJm HiLm HOm HIGMm JiOm IGm #$-0+!'-,#1m#,m GFNLm GiOm HHm &-(1m GOFHm IiNm HMm KNm HiGFm HFm *-0-1'1m ONKm KiGFm HGm GFOLm KiGFm HIm GJKKm HiOm HJm GOFHm IiNm HMm GJKKm HiOm HJm GKKFm HiLm HKm GLIHm JiMm HLm HIGKm HiGFm IFm 12#0'*'""m-m +*$-0+!'A,m#,m $*-0m 1.#!2-m"#m ',$#!!'A,m4'0*m #2*'""m T DMEMDTTTT #m "#"'!Am 3,m +7-0m #1$3#08-m #,m #*m $#,-2'."-m "#*m $032-Zm 7m /3#m #*m - (#2'4-m "#m '#&&-O#.9m#0m#,!-,200m*%B,m+32,2#m/3#m.0-.-0!'-,0m3,-m-m40'-1m!0!2#0#1m 20!2'4-1m"#1"#m#*m.3,2-m"#m4'12m!-+#0!'*Ym-1m+#(-0"-0#1m#,m#12#m!1-m 31! ,m !0!2#0#1m /3#m !+ '0,m #*m 1.#!2-m 2>.'!-m "#*m +#*A,m b'#*m "#m 1.-cm 7m /3#m 0#13*20,mm13m4#8m20!2'4-1m.0m#*m!-,13+'"-0Ym,m$-0+m+91m0#"-,"#"m"#m $032-Zm -m 3,m .'#*m 1',m +,!&1m 7m .-!-m #1!0'230"m .-"0>,m 1#0m *%3,-1m "#m *-1m !0!2#0#1m/3#m.-"0>,m1#0m"#m',2#0<1Ym #m0#!-%'#0-,m*-1m$032-1m"#m.0-6'+"+#,2#mIMFm$+'*'1Ym0m!"m3,m"#m#**1m1#m !0#!'#0-,m"'#8m.*,21m7m.0m!"m.*,2m1#m0#!-%'Am3,m+#*A,Ym #m!-+.00-,m*-1m .09+#20-1m- 1#04"-1m.0m2-"-1m*-1m+#*-,#1m"#m*m+'1+m$+'*'m"#m+-"-m/3#m1#m 1#*#!!'-, ,m /3#**-1m /3#m .0#1#,20,m 3,m 01%-m "'$#0#,!'*m 0#1.#!2-m *-1m "#+91Ym -"-1m *-1m .09+#20-1m 1#m ',20-"3(#0-,m #,m 3,m 1#m "#m "2-1m "#100-**"m .-0m *-1m GJIm .5&)!)OO'/.(.-O ().7*#)-OO Resultados +#(-0"-0#1m "#m '#&&-O #.9m #,m *m /3#m 1#m ',"'! m .0m !"m +#*A,Zm #*m 4'%-0Zm *m 0#1'12#,!'mm->"'-Zm#*m.#1-Zm#*m!-*-0m#62#0'-0Zm#*m#1!0'230"-Zm*m03%-1'""Zm#*m!'#00#Zm*m !4'""Zm#*m!-*-0m"#m*m!0,#Zm#*m 0'6m^!,2'""m#,m8B!0#1_Zm*m"30#8Zm#*m4',"-Zm#*m 1 -0m 7m *1m +#"'"1m "#m $-0+Ym /3#**-1m $032-1m /3#m .0#1#,2 ,m 3,m !09!2#0m "'$#0#,!'"-m7m/3#m.3"'#0m0#13*20m',2#0#1,2#m.0m*m+#(-0m1#m1#*#!!'-, ,m7m1#m *+!#, ,m 131m 1#+'**1Ym 12-1m 0#13*2"-1m ,-m 1#m +3#120,m #,m #12#m 20 (-m 7m /3#m 1-,m"2-1m"#m*m#+.0#1Ym m ,m*m'%30mIYIJm1#m+3#120m3,m#(#+.*-m"#m!A+-m1#m!-+.0 ,m2-"-1m*-1m$032-1m"#m *1m .*,21m "#m 3,m +'1+m $+'*'Ym ,m 4#8m ,*'8"-1m 2-"-1m *-1m !0!2#0#1m 1#m 1#.0 m /3<*m -m /3#**-1m $032-1m /3#m 1#m 1*>,m "#m *-1m .09+#20-1m #129,"0#1Zm .0m .0-"3!'0m +91m 1#+'**m #m ',2#,20m $'(0m #*m $#,-2'.-Ym ,m #12#m #(#+.*-Zm 1#m 1#*#!!'-,Am #*m .0'+#0-m .-0m *m '8/3'#0"m .-0m 1#0m +91m 0#"-,"-m /3#m #*m 0#12-m 7m .-0m *-m 2,2-Zm 3,m $#,-2'.-m',2#0#1,2#m.0m.-"#0m$'(0m#12#m!09!2#0m#,m#*m+#*A,m2'.-mb'#*m"#m1.-cYm m m m m (&30 TDMDEOT0-!#"'+'#,2-m .0m *m 1#*#!!'A,m "#m +#*-,#1m !-,m !0!2#0#1m $#,-2>.'!-1m ',2#0#1,2#1m m ,'4#*m !-+#0!'*Ym,m#12#m#(#+.*-Zm#,m*m'+%#,m13.#0'-0m4#+-1m*-1m+#*-,#1m0#!-%'"-1m"#m#12m$+'*'m^HHNL_m7m GJJm Resultados O .5&)!)OO'/.(.-O ().7*#)-O #,m*m'+%#,m',$#0'-0m#*m+#*A,m1#*#!!'-,"-m.-0m13m!#,23"m$-0+m0#"-,"m#,m!-+.0!'A,mm*m$-0+m #*>.2'!m2>.'!m"#*m+#*A,mb'#*m"#m1.-cYm m #m - 1#040-,m *1m "'$#0#,!'1m $#,-2>.'!1m #,m *-1m $032-1Zm *m '%3*m /3#m .0m *-1m -20-1m "-1m #12"'-1Zm .0m .-"#0m !2*-%0m *%3,-1m $#,-2'.-1m +32,2#1Ym 1m "'12',21m +32!'-,#1m$#,-2>.'!1m1>m!-+-m*1m$+'*'1mHm!-00#1.-,"'#,2#1m1#m"#2**,m#,m*m *mIYHGYm m !+ TDMCBOT#,-2'.-1m#123"'"-1m#,m$032-1Yg29*-%-m"#m'+9%#,#1mIYJYJYm m B+#0-m"#m #,-2'.-m +'*'m $032-1m!-,m#*m $#,-2'.-m +%#,gm +32,2#i+'*'m GFOJm Hm IHm 0'!'-,#1m#,m GGJOm Hm ILm !-*-0i#1!0'230"-m GKFKm Gm INm GOFHm Gm JHm GFOOm Gm IIm #$-0+!'-,#1m#,m GIJJm Gm IMm !'#00#m7m GKINm Gm JFm +*$-0+!'A,m GMKIm Gm JGm GOFHm Gm JHm GGFKm Hm IJm GGIIm Gm IKm 0'!'A,m#,m*m GGJOm Hm ILm $-0+m GKFLm Gm IOm GOFHm Gm JHm HHNLm Gm JIm m DMEMETTTTTTTT ,m#*m1'%3'#,2#m.02"-m1#m&,m0#3,'"-m2-"1m*1m'+9%#,#1m!-00#1.-,"'#,2#1mm*-1m $#,-2'.-1m"#2#!2"-1m#,m*-1m#12"'-1m"#m.*9,23*Zm"#m.*,2m"3*2m7m"#m$032-Ym j32,2#1m#,m#12"'-m"#m.*9,23*[m+9%#,#1m"#m*mGmm*mGOYm j32,2#1m#,m.*,2m"3*2[m+9%#,#1m"#m*mHFmm*mIGYm j32,2#1m#,m$032-[m+9%#,#1m"#m*mIHmm*mJIYm GJKm .5&)!)OO'/.(.-O ().7*#)-OO Resultados 12"'-m"#m.*9,23*m m GJLm .5&)!)OO'/.(.-O ().7*#)-O Resultados O m GJMm .5&)!)OO'/.(.-O ().7*#)-OO Resultados $#"( ) & ) %()) ) )) ) ) &) )& ) m m GJNm % ()) )) ))& ) !()) ')) ) ) ) &) ) ) ) ) ) ) )) )) ) ))& & ) Resultados O .5&)!)OO'/.(.-O ().7*#)-O 12"'-m"#m.*,2m"3*2m m GJOm Resultados T GKFm .5&)!)OO'/.(.-O ().7*#)-OO m .5&)!)OO'/.(.-O ().7*#)-O Resultados O T GKGm Resultados T GKHm .5&)!)OO'/.(.-O ().7*#)-OO T Resultados O .5&)!)OO'/.(.-O ().7*#)-O 12"'-m"#m032-m T GKIm Resultados .5&)!)OO'/.(.-O ().7*#)-OO T m GKJm )&#9(O'/.!(#4OO'&9(O #-/-#9(m m m EMTT T EMBTTTTTTTTT TTT m m#$'!'#,!'m"#m+32!'A,m"#m*m.- *!'A,m"#mm- 2#,'"m#,m#12#m20 (-m&m 1'"-m "#m Gm +32,2#iGZKm Ym 12m #1m 3,m #$'!'#,!'m +#,-0m /3#m /3#**1m "#1!0'21m #,m -201m #1.#!'#1m "'.*-'"#1m !-+-m ,#)*-#-O."&#(m ^GiIFFm _m ^0##,#m 7m !-*YZm HFFI_Zm +>8m ^GiKFFm _m ^'**m 7m !-*YZm HFFJ_m -m !# "m ^Gi _m ^*"5#**m 7m !-*YZm HFFJ_Ym ,m #1.#!'#1m .-*'.*-'"#1m !-+-m #*m 20'%-m 2#20.*-'"#m -m #*m 20'%-m &#6.*-'"#m *-1m 4*-0#1m 2-"4>m1-,m+91m#*#4"-1mGiJFm m7mGiHJm m0#1.#!2'4+#,2#m^*"#m7m!-*YZmHFFK_Ymm ,m #*m +-+#,2-m "#m ','!'0m #12#m 20 (-m ,-m #6'12>m ,',%3,m .- *!'A,m "#m +32,2#1m "#100-**"m#,m+#*A,Em*m.0-2-!-*-m"#m+32%<,#1'1m"#m*1m1#+'**1m$3#m".2"-mm .02'0m"#m-201m#1.#!'#1m7m3,/3#m1#m&'8-m3,m#,17-m.0#4'-m.0m"#2#0+',0m*m"-1'1m A.2'+m "#m Zm *-1m 0#13*2"-1m - 2#,'"-1m ,-1m ',"'!,m /3#m *m "-1'1m 31"m ,-m $3#m .0- *#+#,2#m 13$'!'#,2#Ym ,m ,3#120-m !1-m *1m !-,!#,20!'-,#1m 31"1m "#m m #1234'#0-,m #,m #*m 0,%-m "#m FZKPm &12m GZKPYm ,m !+ '-Zm .0m #*m "#100-**-m "#m *m .- *!'A,m"#mm"#*mZm.02'#0-,m!-,m*m4#,2(m"#m!-,-!#0m*-1m0#13*2"-1m "#m ,3#120-m 20 (-Zm 7m .*'!0-,m !-,!#,20!'-,#1m +91m *21m "#m m ^"#*m GPm *m HP_Ym -0m -20-m *"-Zm "30,2#m #*m .0-2-!-*-m "#m +32!'A,m "#m *1m 1#+'**1m 1#m 0#*'8Am 3,m &'"02!'A,m "#m *1m +'1+1m .0#4'm m *m .*'!!'A,m "#*m +329%#,-Ym 6'12#m 3,m .0-!#1-m "#,-+',"-m )-')*,#'#(!m #,m #*m /3#m *m .0#&'"02!'A,m "#m 1#+'**1m "#1#!"1m .0-.-0!'-,m 3,m %#0+',!'A,m +37m &-+-%<,#m ""-m /3#m !2'4m *-1m 1'12#+1m "#m 0#.0!'A,m "#*m m ^1&0$m 7m 07Zm GOOI_Ym 1m .-0m #**-m /3#m .-1' *#+#,2#m *m .0#&'"02!'A,m0#*'8"m#,m*1m1#+'**1m.3"-m!2'40m*-1m1'12#+1m"#m0#.0!'A,m"#*m m 7m /3'891Zm .0-4-!0m *m !-00#!!'A,m "#m *%3,1m +32!'-,#1m .0-"3!'"1m .-0m #*m m7m#,m!-,1#!3#,!'m (0m*m#$'!'#,!'m"#m*m+32%<,#1'1Ym #,'#,"-m #,m !3#,2m #*m #$#!2-m "#*m +329%#,-m 31"-m ^_m #*m .-0!#,2(#m "#m 1m .0#1#,2#m #,m 3,m %#,m #1m 3,m "#m *1m 40' *#1m /3#m .3#"#m !-,"'!'-,0m *m #$'!'#,!'m "#m +32!'A,Ym #m &,m !-+.0"-m *-1m .-0!#,2(#1m #,m 1m #,m *1m 8-,1m !-"'$'!,2#1m "#m *-1m%#,#1m,*'8"-1Ym0m#*m%#,m#Jm#*m!-,2#,'"-m"#m1m#1m"#m3,mILZMmPZm7m13m '1-$-0+mI#-)J>m2'#,#m3,m!-,2#,'"-m*'%#0+#,2#m13.#0'-0m^IMZJGmP_Ym*m%#,m"#m*m GKKm #-/-#9( O)&#9(O'/.!(#4OO'&9( m 2'#,#m 3,m !-,2#,'"-m "#m 1m "#*m IJZOIm Pm ^ *m JYG_Ym #,'#,"-m #,m !3#,2m #*m #$#!2-m "#*m m #1.#09 +-1m .-"#0m #12 *#!#0m 3,m 0#*!'A,m "'0#!2+#,2#m .0-.-0!'-,*m #,20#m #*m .-0!#,2(#m "#m 1m 7m #*m ,B+#0-m "#m +32,2#1m "#2#!2"-1m #,m !"m%#,Zm.#0-m,-m&m1'"-m1>Ym*m%#,mI#-)J>m#1m#*m/3#m2'#,#m+7-0m.-0!#,2(#m"#m 1#1m131!#.2' *#1mm1#0m+32"1m7m1',m#+ 0%-Zm.0m#12#m%#,m,-m&#+-1m#,!-,20"-m ,',%B,m +32,2#m #,m *m .- *!'A,m m 7m 2,m 1A*-m 3,-m #,m *m .- *!'A,m Ym ,m !+ '-Zm .0m #*m %#,m m #*m .-0!#,2(#m "#m 1m #1m +#,-0m 7m 1#m &,m "#2#!2"-m "-1m +32,2#1m#,m*m.- *!'A,mm7m!320-m#,m*m"#*mYm-0m*-m2,2-Zm#,m#12#m20 (-m .0#!#m/3#m*m.0-.-0!'A,m"#m1m"#*m%#,m,-m1#m&m!-00#*!'-,"-m!-,m*m- 2#,!'A,m "#m +32,2#1m ^ *m JYG_Ym 7m "-1m 08-,#1m /3#m .-"0>,m #6.*'!0m #12#m 0#13*2"-Ym m .0'+#0Zm !-+-m 7m 1#m &m !-+#,2"-m ,2#0'-0+#,2#Zm #1m /3#m ,-m 1#m &m ,*'8"-m 3,m ,B+#0-m 13$'!'#,2#m "#m %#,#1m .0m .-"#0m #12 *#!#0m 3,m 21m "#m +32!'A,m +91m 1'%,'$'!2'4m m ,'4#*m #12">12'!-Ym m 1#%3,"Zm #1m /3#m "# #m 2#,#01#m #,m !3#,2m *m '+.-02,!'m "#*m %#,m #,m !3,2-m m *m $3,!'-,*'""m /3#m 0#*'8Ym 'm 3,m %#,m 2'#,#m 3,m $3,!'A,m 4'2*m .0m *m #1.#!'#Zm #,2-,!#1m *m .0- '*'""m "#m #,!-,200m +32,2#1m &-+-!'%-2-1m#,m#1#m%#,m"'1+',37#m!-,1'"#0 *#+#,2#m.3#12-m/3#m#*m',"'4'"3-m!-,m "'!&m +32!'A,m ,-m 1#0>m 4' *#Zm +30'<,"-m ,2#1m "#m *m .-1' *#m "#2#!!'A,m "#m *m +32!'A,Ymm 0m .-"#0m "#100-**0m 3,m .- *!'A,m B,m +91m #$#!2'4m #,m !3,2-m m 21m "#m +32!'A,m 1#0>m !-,4#,'#,2#m !*!3*0m *1m .*,21m ,#!#10'1m .0m 1#%300m *m - 2#,!'A,m "#m 3,m +32,2#m .0m !"m ,3!*#A2'"-m ,*'8"-Ym #%B,m *+'1m 7m !-*YZm ^HFFM_m !-,-!'#,"-m *m $0#!3#,!'m "#m +32!'A,m - 2#,'"m #,m 3,m .- *!'A,m .-"#+-1m #12'+0m#*m,B+#0-m"#m.*,21m,#!#10'1m.0m!-,1#%3'0m3,m+32!'A,m"#1#"m!-,m 3,m #*#4"m .0- '*'""Ym -0m !-,1'%3'#,2#m 1#m .-"0>m 3+#,20m #*m 2+@-m "#m *m .- *!'A,m&12m- 2#,#0m3,m+32,2#m.-0m!"m 1#m,*'8"m^*+'1m7m!-*YZmHFFM_Ym 12#m 1#0>m 3,m +-"-m "#m 3+#,20m *m #$'!'#,!'m "#m +32%<,#1'1m "#m *m .- *!'A,Zm 3,/3#m#*m.0-!#1-m"#m!0#!'+'#,2-m"#m3,m,B+#0-m2,m#*#4"-m"#m.*,21m1#0>m+37m *0%-m7m!-12-1-m#,m3,m#1.#!'#m!-+-m#*m+#*A,Ym m .02'0m "#m *-1m 0#13*2"-1m "#m #12#m 20 (-Zm #,m m ^.0-7#!2-m HFGFjHFGHm "-,"#Zm #,20#m -20-1m 0#13*2"-1Zm 1#m &m 1#!3#,!'"-m #*m %#,-+m "#*m +#*A,_m 1#m ',!*37Am !-+-m- (#2'4-m*m- 2#,!'A,m"#m-20m.- *!'A,m"#mYmm#+.0#1m'#&&-O#.9m (3,2+#,2#m!-,m#*mjm&,m"#100-**"-m3,m,3#4m.- *!'A,m"#mm m .02'0m "#m 3,m *>,#m .30m "#m +#*A,m 2'.-m e'#*m "#m .-eYm ,m #12m -!1'A,m 1#m &,m +32"-m *1m 1#+'**1m !-,m 3,m .-0!#,2(#m "#m GZKPm "#m m 7m 1#m &,m - 2#,'"-m .0-6'+"+#,2#mIGFFm',"'4'"3-1mHm#,m#*m+-+#,2-m"#m#1!0' '0m#12m2#1'1Zm#,m*-1m GKLm )&#9(O'/.!(#4OO'&9(O #-/-#9(m !3*#1Zm 7m 1#m &,m "#2#!2"-m Nm ,3#4-1m +32,2#1m #,m #*m %#,m >m 7m Im #,m #*m %#,m I#-)J>m^#12-1m0#13*2"-1m1#09,m!-+#,2"-1m!-,m+91m"#2**#m.-12#0'-0+#,2#_Ym m !+ T EMB[m -0!#,2(#m "#m 1#1m 131!#.2' *#1m *m +329%#,-m Zm -m !-,2#,'"-m #,m 1Zm #,m !"m %#,m ,*'8"-Zm7m*m!-+.0!'A,m"#*m,B+#0-m"#m+32,2#1m#,!-,20"-1m#,m!"m.- *!'A,Ymg# #m2#,#01#m#,m !3#,2m /3#m *m 40'#""m 32'*'8"m .0m "#100-**0m *m .- *!'A,m "#*m m ^&0#,2'1_m #0m "'12',2m m *m 32'*'8"m .0m *m .- *!'A,m "#*m m ^'#*m "#m .-_m .-0m *-m 2,2-Zm *-1m .-0!#,2(#1m .-"0>,m 40'0m *'%#0+#,2#Zm7m/3#m*m1#!3#,!'m32'*'8"m.0m*-1m!9*!3*-1m#1m*m"#m*m40'#""mLHjGGIYm m #,m Pm1gm 32,2#1mmm 32,2#1mmm >O ILZMmPm Jm GJm I#-)J>O IMZJGmPm Fm Gm O IJZOImPm Hm Jm GKMm #-/-#9( )'*,#9(O(.,O&-O*)&#)(-OM ,m -201m .- *!'-,#1m 1#m &m "#2#0+',"-m *m #$'!'#,!'m "#m +32!'A,m +#"',2#m #*m ,9*'1'1m#,m3,m,B+#0-m"#m%#,#1m+91m#*#4"-Ym-0m#(#+.*-Zm.0m"#2#0+',0m*m21m "#m +32!'A,m - 2#,'"m #,m *m .- *!'A,m "#m +#*A,m "#100-**"m #,m #*m m 1#m ,*'80-,m GGm %#,#1m ^&+,'j0"1m 7m !-*YZm HFGF_Zm "#m #12#m +-"-m *m 21m "#m +32%<,#1'1m!*!3*"m#1m+91m$' *#Ymm ,m#12#m20 (-m1#m&,m,*'8"-m!320-m%#,#1m#,m"-1m.- *!'-,#1m"'12',21Ym12-m&m .#0+'2'"-m /3#m .-"+-1m #12 *#!#0m *%3,1m !-+.0!'-,#1m #,20#m + 1Ym #%B,m *m *m JYGm - 1#04+-1m /3#m .0m #*m %#,O >m 1#m &,m "#2#!2"-m Jm +32,2#1m #,m *m .- *!'A,m m +'#,201m /3#m #,m *m .- *!'A,m m 1#m &,m "#2#!2"-m GJZm *-m /3#m 0#.0#1#,2m3,m"'$#0#,!'m,-2 *#m#,20#m+ 1m.- *!'-,#1Ym*m+'1+-m!1-m1#m"m#,m #*m %#,m m .3#12-m /3#m #,m *m .- *!'A,m "#*m m 1#m &,m "#2#!2"-m Hm +32,2#1m +'#,201m/3#mJm#,m*m"#*mYmm "-m /3#m 1#m !-,-!#,m *-1m "#2**#1m "#*m .0-2-!-*-m #+.*#"-m .0m *m +32%<,#1'1m 7m "#100-**-m "#m + 1m .- *!'-,#1Zm .-"#+-1m $'0+0m /3#m *m 21m "#m +32!'A,m - 2#,'"m#,m!"m.- *!'A,m&m1'"-m!-,"'!'-,"m 91'!+#,2#m.-0m*m#$'!'#,!'m!-,m /3#m $3#m +32"Zm #1m "#!'0Zm *m "-1'1m "#m +329%#,-m 32'*'8"m 7m #*m .0-2-!-*-m "#m +32%<,#1'1m#+.*#"-Ymm ,m*m *mJYHm1#m0#13+#,m2-"-1m*-1m+32,2#1m#,!-,20"-1m#,m#12#m20 (-Zm2,2-m#,m *m.- *!'A,mm!-+-m#,m*m"#*mZm1>m!-+-m2-"m*m',$-0+!'A,m"#2**"m"#m !"m3,-m"#m#**-1Ym,m*m!-*3+,m"-,"#m1#m"#2**,m*1m$0#!3#,!'1m"#m+32!'A,m1#m #4'"#,!'m /3#m #,m 2-"-1m *-1m %#,#1m *m $0#!3#,!'m "#m +32!'A,m #1m +7-0m #,m *m .- *!'A,m m ^GiIOKm m #,m m 0#1.#!2-m GiGZNm m #,m m #,m #*m .0'+#0m +.*'!A,m"#*m%#,m#JZmGiHLJm m0#1.#!2-mGiOHIm m#,m#*m1#%3,"-m+.*'!A,m"#*m%#,m #JZmGiHZKHm m0#1.#!2-mm,',%B,m+32,2#m#,m#*m%#,mI#-)J>O7mGiMIMm m0#1.#!2-m GiGZJGm m #,m *m _Ym *m +'1+-m 2'#+.-Zm m .#10m "#m /3#m #,m *m .- *!'A,m m *m $0#!3#,!'m "#m +32%<,#1'1m #1m +7-0Zm #,m *%3,-1m !1-1m !-+m #*m "#*m %#,m I#-)J>m 1'%3#m 1'#,"-m +37m (Ym 12#m "2-m !-00- -0m *m &'.A2#1'1m "#m /3#m #6'12#,m *%3,-1m %#,#1m /3#Zm .-0m +-2'4-1m 2-"4>m "#1!-,-!'"-1Zm 0#13*2,m +91m "'$>!'*#1m "#m +32%#,'80Ymm m m m m m GKNm )&#9(O'/.!(#4OO'&9(O #-/-#9(m !+ TEMC[m *m0#13+#,m"#m*-1m+32,2#1m#,!-,20"-1m#,m!"m.- *!'A,m7m.0m!"m%#,Zm!-,m"#2**#m "#*m 2'.-m "#m !+ '-m "#m 1#Zm #*m #$#!2-m "#m *m +32!'A,m m ,'4#*m +',-!>"'!-Zm #*m ,-+ 0#m "#m *m $+'*'Zm *m 1#%0#%!'A,m Hm .0m /3#**-1m +32,2#1m /3#m 1#m &,m .-"'"-m #123"'0Zm *m $0#!3#,!'m "#m +32!'A,Zm #*m $#,-2'.-m#,m!1-m"#m& #0m1'"-m#123"'"-Zm7m$',*+#,2#m#*m4*-0mYm^gm2-1m#6.*'!"-1m#,m#*m.02"-m JYHYHZm *mJYImgg2-1m#6.*'!"-1m#,m#*m.02"-mIYHYGYIZm *mIYMYm m KFFm Im Im &0GKK&0m GNNFm jm ,20A,mHm im m OKOm jm 6A,mGm HNOm *3OM71m KIm jm 6A,mGm HOJm &#ON&#m HKIHm jm ,20A,mGm im m GJHFm jm GiOHI m GiIOKm m *-0m m jm FYFFm jm FYFFm jm jm jm jm jm FYFHm jm jm jm jm 6A,mHm JFGm *GIJ*m GHHOm jm jm FYGFm 6A,mHm JFMm *7GIL*m JJJm jm jm FYFFm ,20A,mHm im m GHNMm jm jm jm im m GGGKm jm jm jm jm jm jm jm ,20A,mHm im >O .0'+#0 GGLOm GGm -*&##(!O m m GiGZN m #,-2'.-m JLKm +32!'A,m 6A,mHm 0#!3#,!'m FKiFIiFFgm ^ii_m FOiFMiFNgm KMm Hm HFILm 1#%0#%!'A,m 0%HK71m *3GHO71m -1'!'A,m MJm INKm 6A,im 6A,mGm 6A,mHm ,20A,m B+#0-m +32,2#1m +@-m GGLOm Gm Hm$+'*'m m KFFm + '-mm >O +.*'!A,m^. _m #,m i- *!'A,m m GLLMm ,20A,mIm im m HLJLm jm jm ,20A,mIm im m GHIIm jm jm jm 6A,mJm LGLm *3HFL71m HFLFm jm jm FYFOm ,20A,mJm im m HFIKm jm jm jm Iamm im m GILNm jm jm jm Iamm im m HGLIm jm jm jm ,20A,mIm m 1#m "#*m GiHLJm m ',20A,m I#-)J Jm m GFGJm Fm jm jm jm jm jm Fm jm jm GFGJm Gm 6A,mGm GHNm 0%JI71m GKNMm jm GiHYKH m jm GYFFm ,20A,mGm im m GGKGm FJiFMiFJggm jm jm m I#-)J Jm m m O m GGNNm Hm 6A,mHm KLFm #0KJF&#m INJm FLiFOiFFggm GiGYJG m *,2m * ',m#,m FYFFm Im O GGNNm Jm 6A,mGm IOKm #0JNK&#m GGNHm jm GiMIM m jm FYFGm GKOm #-/-#9( m )'*,#9(O(.,O&-O*)&#)(-OM ,20A,mGm im jm HJOKm jm jm jm jm ,20A,mGm im jm GJLFm jm jm jm jm ,20A,mGm im jm GHHLm jm jm jm jm m ,m #6.*'!!'A,m .0m *-1m 0#13*2"-1m - 2#,'"-1m #,m #*m %#,m I#-)J>Zm .-"0>m 1#0m #*m +-2'4-m 7m !-+#,2"-m ,2#0'-0+#,2#Zm /3#m *m +32!'A,m .0-4-!0m ',"'4'"3-1m ',4' *#1m7m.-0m*-m2,2-m,3,!m.3"'#0,m"#2#!201#m.-0/3#m,-m**#%,mm"#100-**01#Ym m *#2*'""m -m *m $*2m "#m +32,2#1m .3#"#m 1#0m .0-4-!"m 2,2-m .-0m #*m #$#!2-m "#m *m +32!'A,m#,m#*m%#,m,*'8"-m!-+-m.-0m#*m#$#!2-m"#m-201m+32!'-,#1m/3#m!-,2'#,#m #*m+'1+-m+32,2#m0#.02'"1m*#2-0'+#,2#m.-0m2-"-m#*m%#,-+Ym'(9,"-,-1m#,m*m $0#!3#,!'m"#m*m.- *!'A,m+91m#$'!'#,2#m^_m#12#m%#,m.0#1#,2m3,m$0#!3#,!'m"#m Gm+32,2#m!"mHZKHm Zm!*0+#,2#m+37m (m1'm*m!-+.0+-1m!-,m*m"#*m%#,mm ^GiMIMm _m -m !-,m *m "#*m 1#%3,"-m +.*'!A,m "#*m %#,m >O ^GiHLJm _Ym ,m "#m *1m $3,!'-,#1m"#*m%#,mI#-)J>m#1m*m"#m73"0mm#12 '*'80m#*m!-+.*#(-m.0-2#'!-m.0m *m ','!'!'A,m "#m *m 20"3!!'A,m "#m *1m .0-2#>,1m ^0-5,',%m 7m !-*YZm GOOH_Zm $3,!'A,m 91'!m .0m *m !<*3*Ym -0m #12#m +-2'4-m .-"0>+-1m .#,10m /3#m +32,2#1m !-,m 3,m !+ '-m/3#m,-m.#0+'2'#0m*m#12 '*'""m"#m*m.0-2#>,mI#-)J>m#,m#*m!-+.*#(-m"#m ','!'!'A,m "#m *m 20"3!!'A,m 7m .-0m *-m 2,2-Zm ,-m .#0+'2'#0m *m 20"3!!'A,m "#m !'#021m .0-2#>,1Zm&0>m/3#m,-m$3#0,m4' *#1Ymm m#$'!'#,!'m"#m+32!'A,m- 2#,'"m#,m3,m.- *!'A,m"#mm"#m2-+2#m"-,"#m 1#m ,*'80-,m GNm %#,#1Zm 3,-m "#m #**-1m #*m %#,m >Zm $3#m "#m GiKMJm m ^'0-,m 7m !-*YZm HFGF_Ym ',m #+ 0%-Zm .0m #*m %#,m I#-)J>m *m #$'!'#,!'m "#m +32!'A,m $3#m "#m GiGGGFm Ym 12#m "2-m !-',!'"#m !-,m *-1m 0#13*2"-1m - 2#,'"-1m #,m #12#m 20 (-m 7m "#+3#120m !-+-m .0m !'#02-1m %#,#1m *m #$'!'#,!'m "#m +32!'A,m .3#"#m 1#0m +91m (m 0#1.#!2-m *m #$'!'#,!'m +#"'m #,m *m .- *!'A,Zm .0- *#+#,2#m "# '"-m m /3#m 13m $3,!'A,m #1m +91m 4'2*m.0m#*m-0%,'1+-m/3#m-20-1m%#,#1m!-,m3,m21m"#m+32!'A,m+3!&-m+91m*2Ymm $ GLFm .)-OO&-O'/.#)(-O#(.# #-O #-/-#9(m m m EMCT T T T T T T T TT m EMCMBTTPTQT -"#0m 0#*!'-,0m #*m $#,-2'.-m "#m 3,m +32,2#m !-,m 3,m +32!'A,m !-,!0#2m .#0+'2#m !-,$'0+0m*m$3,!'A,m"#*m%#,Ym0m#**-Zm&!#m$*2m!0!2#0'80m '#,m*-1m+32,2#1m7m 1#m m ,'4#*m +-0$-*A%'!-Zm +#2 A*'!-Zm '-/3>+'!-m -m +#"',2#m -20-1m ,9*'1'1m /3#m !0!2#0'!#,m!-,m#6!2'23"m#*m#$#!2-m"#*m%#,m+32"-Ym *m%#,mm0#*'8m3,m$3,!'A,m"#2#0+',,2#m.0m*m '-1>,2#1'1m"#m!0-2#,-'"#1m7m #,m!-,1#!3#,!'Zm.0m/3#m1#m!-+3*#,m.'%+#,2-1m#,m*m.*,2Ymm,-m$3,!'-,*'""m -m#*m1'*#,!'+'#,2-m"#*m%#,mm.0-4-!m$#,-2'.-1m* ',-1Zm!-+-m1#m&m"#+-120"-m #,m-201m#1.#!'#1m!-+-m,#)*-#-m-m00-8m^0-*m7m3,28ZmHFFG\m02&+,,ZmHFFN_Ym -0m#**-Zm1#m#1!-%'Am#*m%#,mm!-+-m!-,20-*m$#,-2>.'!-m"#m*m.- *!'A,m.3#12-m/3#m *m"#2#!!'A,m"#m+32,2#1m.0m#12#m%#,m,-m0#/3#0>m"#m#,17-1m!-+.*#(-1Ym,!-,200m 3,m.*,2m* ',m*m+320mm"#+-1200>m,-m1A*-m*m$3,!'-,*'""m"#*m%#,Zm1',-m *m #$'!'#,!'m "#m *m .- *!'A,m "#m m 7m #*m +<2-"-m 31"-m .0m "#2#!20m *-1m +32,2#1Ym ,m *m .3#12m m .3,2-m "#*m +<2-"-m 1#m "#2#!20-,m Hm +32,2#1m #,m #*m %#,m m #,m *m .- *!'A,m Zm 3,-m "#m #**-1m #,m 8-,m !-"'$'!,2#m ^+32,2#m INJ_m 7m !-,m 3,m 4*-0m m"#mFYFFm/3#m!-,$'0+ m/3#m*m+32!'A,m.-">m$#!20mm*m$3,!'-,*'""m"#m*m .0-2#>,Ym 01m %#0+',0m HFm 1#+'**1m Hm "#m *m $+'*'m +32,2#m INJm 1#m - 234'#0-,m .*9,23*1m!-,m3,m$#,-2'.-m/3#m+-120 m*-1m!-2'*#"-,#1m*2#0"-1m#,m13m+-0$-*-%>Zm .#0-m ,-m 1#m - 234-m ,',%3,m .*,2m * ',Ym ',m #+ 0%-Zm *m %#0+',0m 1#+'**1m Im - 2#,'"1mm.02'0m"#m*m32-$#!3,"!'A,m"#m3,m&#2#0-!'%-2-mHm.0m*m+32!'A,Zm1'm 1#m - 234-m 3,m ',"'4'"3-m * ',-m ^'%30m JYG_Ym "#+91Zm 1#m !-+.0- Am +#"',2#m #*m ,9*'1'1m "#m *m 1#!3#,!'m "#m m /3#m #0m *m B,'!m .*,2m &-+-!'%-2m .0m *m +32!'A,Ym -0m *-m 2,2-Zm *m "#2#!!'A,m "#m #12#m +32,2#m "#+-120Am /3#m #*m +<2-"-m m 1#m #12 m .*'!,"-m !-00#!2+#,2#Zm 7m /3#m 1#m .-">,m - 2#,#0m $#,-2'.-1m +32,2#1m#,m,3#120m.- *!'A,Ym m GLGm #-/-#9( .)-OO&-O'/.#)(-O#(.# #- m m (&30 MEMB[m*9,23*m!-,m$#,-2'.-m* ',-m'"#,2'$'!"m#,m*m$+'*'mINJZm+32,2#m#,m#*m%#,mm^'2-#,-m "#12301_Ym0'+#0m+32,2#m"#2#!2"-m%#,-2>.'!m7m$#,-2>.'!+#,2#m7m/3#m"#+3#120m*m#$'!'#,!'m"#m*m .- *!'A,m"#mm"#mLHjGGIYm m 1m '+.-02,2#m "#12!0m /3#m #,m #*m +-+#,2-m "#m ','!'0m #12#m 20 (-m ,-m 1#m !-,-!>m *m 1#!3#,!'m!-+.*#2m"#*m%#,mm#,m+#*A,m7m.-0m*-m2,2-Zm#*m"'1#@-m"#*m+.*'!A,m"#m m1#m&'8-mm.02'0m"#m3,m3,'%#,m^OFMF_Ym!23*+#,2#Zm7m%0!'1mm/3#m1#m "'1.-,#m "#m *m 1#!3#,!'m "#*m %#,-+m "#*m +#*A,Zm 1#m &m .-"'"-m "#2#0+',0m *m #1203!230m!-+.*#2m"#*m%#,mZm/3#m!-,12m"#mGJm#6-,#1Ymm m EMCMCT$ETPTTTTTTEQT *m%#,m#Jm&m1'"-m#*m%#,m#,m#*m/3#m1#m&,m"#2#!2"-m+91m+32,2#1m#,m#12#m20 (-Ym ,m #12#m %#,Zm 1#m &,m '"#,2'$'!"-m +32!'-,#1m ,230*#1m 0#1.-,1 *#1m "#m '+.#"'0m *m ',2#0!!'A,m #,20#m #*m $!2-0m "#m ','!'!'A,m 7m *m !"#,m ',$#!2'4m "#m m .-1'2'4m "#m *%3,-1m4'031m^- %*'m7m0,2ZmHFFL_Ym- %*'m7m0,2m#,mHFFLm0#4'10-,m*-1m $!2-0#1m "#m ','!'!'A,m "#m *m 20"3!!'A,m "#m *%3,1m #1.#!'#1m 7m 13m ',2#0!!'A,m !-,m 4'031m 7m !A+-m *%3,1m +32!'-,#1m .0-.-0!'-, ,m 0#1'12#,!'m ,230*m m "'4#01-1m .-2'4'031Ym-+.00-,m*m1#!3#,!'m.0-2#'!m"#m*-1m%#,#1m*0,<m"#m.#.',-m^*-#/'O ((/'_Zm *).;m "#m 2-+2#m ^)&(/'O &3)*,-#/'_Zm ');m "#m *#!&3%m ^./.O -.#0_m 7m -';m "#m %3'1,2#m ^#-/'O -.#0/'_Ym ,m #12#m *',#+'#,2-m 1#@*0-,m *1m "'$#0#,!'1m +',-!>"'!1m #,20#m *-1m %#,-2'.-1m 0#1'12#,2#1m 7m *-1m 131!#.2' *#1m ^'%30m JYHZm #,m $-,"-m ,#%0-_m #,m !"m 3,m "#m *1m #1.#!'#1m !'2"1Ym + '<,m '"#,2'$'!0-,m "-1m GLHm .)-OO&-O'/.#)(-O#(.# #-O #-/-#9(m 0#%'-,#1m^'%30mJYHZm8-,1m$3!1'm7m83*m230/3#1_m"A,"#m1#m!-,!#,20,m3,m+7-0m ,B+#0-m "#m .-*'+-0$'1+-1m #,20#m *-1m $#,-2'.-1m 131!#.2' *#1m 7m 0#1'12#,2#1Ym "#+91Zm + 1m0#%'-,#1m!-,$-0+,m&))*-O)O*8-1m#62#0,-1m#,m*m#1203!230mIm"#m*m.0-2#>,Ym ,m#12#m+'1+-m*',#+'#,2-m.0-2#'!-m&#+-1m',!*3'"-m#*m%#,m#Jm"#m+#*A,Zm!-,m*m &'12'"',m #,m *m .-1'!'A,m HHNm +0!"m #,m *,!-m 7m $-,"-m 83*m +0',-m ^'#2-m 7m !-*YZm HFFL_m ^'%30m JYH_Zm 0#1.-,1 *#m "#m *m 0#1'12#,!'m m m ^(-0_Zm #*m %#,m -02A*-%-m #,m !# "m ^),/'O 0/&!,_m ,3'm 0#1.-,1 *#m "#m *m 0#1'12#,!'m m m ^'031m "#*m -1'!-m +0'**-m #,m # "_m 7m *-1m +32,2#1m #,!-,20"-1m +#"',2#m m #,m #12#m20 (-m^'%30mJYHZm#,m$-,"-m0-(-m7m4#0"#_Ym#m#12#m+-"-m.-"#+-1m!-+.0- 0m /3#m*1m+32!'-,#1m"#2#!2"1m#,m#12#m20 (-m#129,m*-!*'8"1m#,m"'12',21m0#%'-,#1m m *1m "#1!0'21m ,2#0'-0+#,2#m #,m -201m #1.#!'#1Ym *m +'1+-m 2'#+.-Zm 1#m &m .-"'"-m "#2#0+',0m/3#m*1m+32!'-,#1m*3GHO71m^$+'*'mKM_Zm*GIJ*m^$+'*'mGHHO_m7m *7GIL*3m ^$+'*'m JJJ_m .0-4-!,m 3,m !+ '-m "#m +',-9!'"-m #,m 0#%'-,#1m +37m !-,1#04"1m"#m*m.0-2#',Zm.-0m*-m2,2-m13m#$#!2-m1#m.0- *#+#,2#m+7-0m/3#m*1m +32!'-,#1m '"#,2'$'!"1m #,m 8-,1m +#,-1m !-,1#04"1Zm *1m +32!'-,#1m 0%HK71m ^$+'*'mHFIL_Zm*3OM71m^$+'*'mKI_m7m*m*3HFL71m^$+'*'mHFLF_Ym1m+32!'-,#1m 1'*#,!'-11m ,-m .0-4-!,m !+ '-m "#m +',-9!'"-m 7m .-0m *-m 2,2-m ,-m $#!209,m m *m $3,!'-,*'""m"#m*m.0-2#>,m^&#ON&#m^$+'*'mHKIH_m7m&0GKK&0m^$+'*'mGNNF__Ymm '(9,"-,-1m #,m #*m *',#+'#,2-m .0#1#,2"-m #,m *m '%30m JYHm #,!-,20+-1m #*m .0'+#0m +32,2#m "#2#!2"-m #,m *m .- *!'A,m m #,m *m .-1'!'A,m HKm "#m *m 1#!3#,!'m +',-!>"'!m"#*m%#,m#Jm#,m+#*A,O^*-1m+32,2#1mm#129,m"#2**"-1m#,m$-,"-m 0-(-_Ym12m+32!'A,m.#02#,#!#mm*m$+'*'mHFILm7m#*m!+ '-m/3#m.0-4-!m#1m"#m3,m 0%',',m m 3,m *'1',Ym + -1m +',-9!'"-1m !-,2'#,#,m #*m 0"'!*m "#m !"#,m !0%"-m .-1'2'4+#,2#m .#0-m *m 0%',',m !-,2'#,#m *m $',*m "#*m 0"'!*m "-1m %03.-1m +',-m +'#,201m/3#m*m*'1',m,-Ym0m#12m+32!'A,m#*mm.0#"'!#m3,m4*-0mFYFFm7m.-0m*-m 2,2-m3,m.-1' *#m#$#!2-m#,m*m$3,!'-,*'""m"#m*m.0-2#>,Ym,m#12#m!1-m1#m#,!3#,20m #,m 3,m 0#%'A,m +37m .-!-m !-,1#04"m 7m .-0m *-m 2,2-m /3'891m 3,m 0#%'A,m ,-m 2,m '+.0#1!',"' *#m.0m*m!-00#!2m$3,!'-,*'""m"#m#JYmm m m m m m m m GLIm #-/-#9( .)-OO&-O'/.#)(-O#(.# #- pot1 pvr2 rym nsv sbm1 mo1 MAAAEMERTMSFDAAEKLKAAD---GGGGEVDDELEEGEIVEES----NDTASYLGKEIT MATAEMEKTTTFDEAEKVKLN------ANEADDEVEEGEIVEET----DDTTSYLSKEIA MAEDTETRPASAGAEER------------------EEGEIADDG----DGSAAAAAGRVS MVVEDSMKATSAEDLSNSIANQNPRGRGGDEDEELEEGEIVGDDD--LDSSNLSAS-LVH MVVEETPKSIITDDQITTNPN-----RVIEDDNNLEEGEILDED----DSSATSKP-VVH MKSEE-QKLIDVNKHRGVRSD-------GEEDEQLEEGEIVGGDADTLSSSSSSRPGTAI * : ***** ..: 53 50 38 57 50 52 pot1 pvr2 rym nsv sbm1 mo1 VKHPLEHSWTFWFDNPTTKSRQTAWGSSLRNVYTFSTVEDFWGAYNNIHHPSKLIMGADF TKHPLEHSWTFWFDNPVEKSKQDAWGSSLRNVYTFSTVEDFWGAYNNIHHPSKLVVGADL -AHPLENAWTFWFDNPQGKSRAVAWGSTIHPIHTFSTVEDFWSLYNNIHHPSKLNVGADF QPHPLEHSWTFWFDNPSAKSKQATWGASIRPIYTFSTVEEFWSVYNNIHHPSKLAMRADL QPHLLENSWTFWFDTPAAKSKQDDWGSSMRPIYTFSTVEEFWSIYNNIHHPGKLAVGADF AQHPLEHSWTFWFDTPSAKSKQVAWGSSMRPIYTFSSVEEFWSLYNNIHRPSKLAQGADF * **::*** **.* **: **:::: ::***:**:**. *****:*.** **: 113 110 97 117 110 112 pot1 pvr2 rym nsv sbm1 mo1 HCFKHKIEPKWEDPVCANGGTWKMSFSKGKSDTSWLYTLLAMIGHQFDHGDEICGAVVSV HCFKHKIEPKWEDPVCANGGTWKMSFSKGKSDTSWLYTLLAMIGHQFDHEDEICGAVVSV HCFKDKIEPKWEDPICANGGKWTISCGKGKSDTFWLHTLLALIGEQFDFGDEICGAVVSV YCFKHKIEPKWEDPVCANGGKWTVNFPRGKSDNGWLYTLLAMIGEQFDCGDEICGAVVNV YCFKHKIEPKWEDPICANGGKWTANYPKGKSDTSWLYTLLAMIGEQFDHGDEICGAVVKV YCFKNKIEPKWEDPVCANGGKWTMTFTKAKSDTCWLYTLLAMIGEQFDHGDDICGAVVNV :***.*********:*****.*. . :.***. **:****:**.*** *:******.* 173 170 157 177 170 172 pot1 pvr2 rym nsv sbm1 mo1 RAKGEKIALWTKNAANETAQVSIGKQWKQFLDYSDSVGFIFHDDAKRLDRNAKNRYTV RGKGEKISLWTKNAANETAQVSIGKQWKQFLDYSGSVGFIFHDDAKRLDRNAKNRYTV RKNQERVAIWTKNAANETAQISIGKQWKEFLDYKDSIGFVVHEDAKRSDKGAKNRYTV RSGQDKISIWTKNASNEAAQASIGKQWKEFLDYNESIGFIFHDDAKKFDRLAKNKYMV RGRAEKISIWTKNASNEAAQVSIGKQWKEFLDYNETMGFIFHDDARKLDRNAKNKYVV RARQEKIALWTKNAANESAQLSIGKQWKEFIDYNDTIGFIFHEDAKTLDRSAKNKYTV * :::::*****:**:** *******:*:**. ::**:.*:**: *: ***:* * 231 228 215 235 228 230 (&30 T EMC[m *',#+'#,2-m +#"',2#m &/-.&m "#m *m .0-2#',m #Jm "#m "'12',21m #1.#!'#1Ym #m "#12!m #,m $-,"-m,#%0-m*m*-!*'8!'A,m"#m*-1m+',-9!'"-1m/3#m"'$'#0#,m#,20#m*-1m%#,-2'.-1m131!#.2' *#1m7m0#1'12#,2#1mm m .-2'4'031m "#m .'+'#,2-m ^*-#/'O ((/'Fm *0,<_Zm 2-+2#m I)&(/'O &3)*,-#/(Fm *).;_Zm *#!&3%m ^./O -.#0Zm');_Zm%3'1,2#m^#-/'O-.#0/'Fm-';_Zm+#*A,m^//'#-O'&)Zm(-0_m7m!# "m^),/'O0/&!,Zm,3'_Ym 1m.02#1m!-*-0#"1m#,m$3!1'm7m83*m230/3#1m0#.0#1#,2,m*1m8-,1m!-,m+91m!+ '-1m"#m+',-9!'"-1m7m m 13m 4#8m 8-,1m +91m #6.3#121m *m #62#0'-0m 2*m 7m !-+-m "#2#0+',m *m !-,$'%30!'A,m #,m Im "#m *m .0-2#>,m ^- %*'m7m0,2ZmHFFL_Ym,m0-(-m*1m+32!'-,#1m"#2#!2"1m+#"',2#mm#,m*m.- *!'A,mm7m #,m4#0"#m*1m+32!'-,#1m"#2#!2"1m#,m*m.- *!'A,m"#*mYm m 1m1'%3'#,2#1m+32!'-,#1m/3#m#,!-,20+-1m.#02#,#!#,mm*1m$+'*'1mKIm7mHKIHm^#,m #12#m!1-m#,m4#0"#m7m/3#m1#m"#2#!20-,m#,m*m.- *!'A,m"#*m_Ym,m*m$+'*'mKIm *m+32!'A,m1#m#,!3#,20m#,m*m.-1'!'A,mOMm7m.0-4-!m3,m!+ '-m"#m9!'"-m%*329+'!-m m *'1',Ym *m m #,m #12#m !1-m .0#"'!#m 3,m .3,23!'A,m "#m FYFHm 7m .-0m *-m 2,2-m 3,m .-1' *#m !+ '-m #,m *m $3,!'-,*'""m "#m *m .0-2#>,Ym "#+91Zm #*m !+ '-m "#m 9!'"-m %*329+'!-mm*'1',m.0-4-!m2+ '<,m3,m!+ '-m"#m!0%m^"#m,#%2'4-mm.-1'2'4-_m/3#m .-"0>m $#!20m #,m *m ',2#0!!'A,m !-,m -20-1m +',-9!'"-1m 7m .-0m *-m 2,2-m #,m #*m .*#%+'#,2-m"#m*m.0-2#>,Ym,m.-1' *#m!+ '-m#,m*m!-,$-0+!'A,m"#m*m.0-2#>,mm ,'4#*m .0'+0'-m 3m -20-1m ,'4#*#1m 13.#0'-0#1m .-"0>m $#!20m m *m $3,!'-,*'""m "#m *m GLJm .)-OO&-O'/.#)(-O#(.# #-O #-/-#9(m .0-2#>,m-mm13m',2#0!!'A,m!-,m13m*'%,"-Ymm$+'*'mHKIHm2'#,#m*m+32!'A,m(312-m #,m *m .-1'!'A,m !-,2'%3m m *m ,2#0'-0m #,m #*m +',-9!'"-m ,B+#0-m ONYm -m - 12,2#Zm *m +32!'A,m #1m 1'*#,!'-1Ym -,m #12#m *',#+'#,2-m &#+-1m .-"'"-m - 1#040m /3#m &7m !'#021m 0#%'-,#1m "#m *m 1#!3#,!'m .0-2#'!m +91m 131!#.2' *#1m m 1#0m +32"1m -m /3#m .#0+'2#,m *m +32!'A,Zm .3#12-m /3#m *m .0- '*'""m "#m +320m "-1m +',-9!'"-1m !-,2'%3-1m-m+37m!#0!,-1m#1m (Ymm ,m *m 0#%'A,m "#*'+'2"m .-0m *-1m +',-9!'"-1m GHOm *m GKKm &#+-1m "#2#!2"-m !320-m +32,2#1Zm"-1m#,m!"m.- *!'A,Ymm+32!'A,m!-00#1.-,"'#,2#m*m+',-9!'"-mGHOm $3#m "#2#!2"m #,m *m $+'*'m KMm "#m *m .- *!'A,m Ym 12#m !+ '-m #1m 1'%,'$'!2'4-m ^SFYFF_m .3#12-m /3#m .0-4-!m 3,m !+ '-m "#m 9!'"-m %*329+'!-m m *'1',Ym 1m +32!'-,#1m"#m*1m$+'*'1mGHHOm7mJJJm"#m*m.- *!'A,mm#129,m*-!*'8"1m!-,m 1A*-m 3,m +',-9!'"-m "#m 1#.0!'A,Ym + 1m .0-"3!#,m !+ '-m "#m +',-9!'"-Zm *m .0'+#0m "#m *,',m m 4*',m ^+ -1m &'"0-$A '!-1_m !-,m 3,m 4*-0m "#m m "#m FYGFm +'#,201m/3#m*m1#%3,"m"#m%*'!',mm9!'"-m%*329+'!-m!-,m3,m4*-0m"#mm"#mFYFFYm 12#mB*2'+-m.0#!#m/3#m.-"0>m$#!20m+91mm*m$3,!'-,*'""m"#m*m.0-2#>,m.3#12-m /3#m #*m !+ '-m #1203!230*m 2+ '<,m .-"0>m 1#0m +91m !#,23"-Ym m %*'!',m #1m 3,m +',-9!'"-m+37m.#/3#@-m7m13m0"'!*m1#m 1m#,m3,m92-+-m"#m&'"0-%#,-Zm+'#,201m /3#m#*m9!'"-m%*329+'!-m#1m3,m+',-9!'"-m!0%"-m,#%2'4+#,2#m7m!-,m3,m0"'!*m +3!&-m+91m%0,"#m/3#m1#m#1203!230m#,m3,m!"#,m"#m20#1m!0 -,-1m!-,m3,m%03.-m !0 -6'*-Ym ',*+#,2#Zm *m !302m +32!'A,m #,m #12m 0#%'A,m $3#m '"#,2'$'!"m #,m *m $+'*'m GNNFm "#m *m .- *!'A,m Zm .#0-m #,m #12#m !1-m *m +32!'A,m #1m 1'*#,!'-1Ym #m "#12!0m /3#m *1m 20#1m +32!'-,#1m ^KMZm GHHOm 7m JJJ_m #129,m *-!*'8"1m #,m 3,m 0#%'A,m +37m !-,1#04"m ^'%30m JYH_Ym m (m 21m "#m .-*'+-0$'1+-1m #,m #12m 0#%'A,m ,-1m.-"0>m',"'!0m/3#m#1m'+.-02,2#m.0m*m$3,!'-,*'""m"#m*m.0-2#>,Ym ,m *m .-1'!'A,m HFLm #,!-,20+-1m #*m B*2'+-m +32,2#m "#2#!2"-m #,m *m $+'*'m HFLFm .#02#,#!'#,2#mm*m.- *!'A,mYm,m#12#m!1-m#*m!+ '-m.0-"3!'"-m#1m2+ '<,m"#m 9!'"-m %*329+'!-m m *'1',Ym 12m B*2'+m +32!'A,m 1#m #,!3#,20m #,m 3,m 8-,m ,-m 2,m !-,1#04"m!-+-m.3#"#m4#01#m#,m*m'%30mJYHm7m.-0m#**-m13m4*-0mm#1m2+ '<,m +7-0m^FYFO_Ym #m 3,m 2-2*m "#m -!&-m +32,2#1m #,m 0#%'A,m #6A,'!m "#*m %#,m #JZm 1#'1m .0-"3!#,m !+ '-m "#m +',-9!'"-m 7m 20#1m "#m #**-1m 1-,m "#m 9!'"-m %*329+'!-m m *'1',Ym 3,/3#m .0#!#m /3#m *m +32!'A,m +#"',2#m m #1m 2-2*+#,2#m *#2-0'Zm #,m ,3#120-m !1-m &m & '"-m3,m!'#02m2#,"#,!'mm+320m*%3,1m0#%'-,#1m+91m/3#m-201m7mm13m4#8Zm&m & '"-m20#1m!1-1m"#m1#'1m#,m/3#m#*m!+ '-m&m1'"-m#*m+'1+-m^i_Ymm GLKm #-/-#9( .)-OO&-O'/.#)(-O#(.# #- ,m *m '%30m JYHm 2+ '<,m 1#m .3#"#m - 1#040m !-+-m ,',%3,m "#m *1m +32!'-,#1m "#2#!2"1m1#m*-!*'8m#,m*1m0#%'-,#1m"#m#Jm!-,m*2-m!-,2#,'"-m#,m.-*'+-0$'1+-1m #,20#m*1m40'#""#1m0#1'12#,2#1m7m*1m131!#.2' *#1m"#m-201m#1.#!'#1Ym !23*+#,2#m #6'12#,m +3!&1m &#00+'#,21m ',$-0+92'!1m .0m .-"#0m #123"'0m !-,m "#2**#m !-+-m $#!2,m *1m +32!'-,#1m m *m $3,!'-,*'""m "#m 3,m .0-2#>,Ym ,m #12#m 20 (-m1#m&m31"-m+7-0'20'+#,2#m#*mYm ,m HFFLm 3*',m 7m #,')-$$m .3 *'!0-,m 3,m #123"'-m "-,"#m .0#1#,20-,m 3,m 1#0'#m "#m +<2-"-1m7m&#00+'#,21m.0m.-"#0m.0#"#!'0m*-1m#$#!2-1m"#m!+ '-1m"#m+',-9!'"-1m #,m *m .0-2#>,Zm +3!&-1m "#m #**-1m "'1.-,' *#1m 4'm 5# Ym ,-m "#m #**-1m #1m m ^".)&)!3O '/..#)(-_m ^-12m 7m ,"#0Zm GOOI_m 7m 3,/3#m #12<m "'1#@"-m .0m "#2#!20m +32!'-,#1m#,m&3+,-1m0#13*2m#1.#!'*+#,2#mB2'*m.0m*m.0#"'!!'A,m"#m#1203!2301m 1#!3,"0'1m"#m.0-2#',1Ym ,m ,3#120-m !1-m 1#m &,m &#!&-m 2+ '<,m 1'+3*!'-,#1m #,m Im !-,m &#00+'#,21m ',$-0+92'!1m /3#m 1#m &,m .0#1#,2"-m #,m #*m .02"-m "#m #13*2"-1Zm 32'*'8,"-m 7-*Ym ',m #+ 0%-Zm 0#13*2m 2+ '<,m ',2#0#1,2#m &!#0m 3,m #123"'-m "#2**"-m "#m *m .0#"'!!'A,m "#m #1203!2301m 1#!3,"0'1m #,m *m 1#!3#,!'m .0-2#'!Ym 121m #1203!2301m 1-,m*1m.0'+#01m$#!2"1m7m/3#m1#m!-,12037#,mm204<1m"#m*1m',2#0!!'-,#1m#,20#m +',-9!'"-1Ym -0m #**-m 31+-1m #12m &#00+'#,2m ^_m #,m *m /3#m .-"#+-1m - 1#040m *m 1#!3#,!'m .0-2#'!m "#m #Jm !-,m *m .0#"'!!'A,m #1203!230*m !-00#1.-,"'#,2#m.0m!"m+',-9!'"-m^'%30mJYI_Ym 1m +32!'-,#1m !-00#1.-,"'#,2#1m m *1m $+'*'1m GHHOm 7m JJJm !-,m !+ '-1m #,m *1m .-1'!'-,#1m GIJm 7m GILm #129,m *-!*'8"1m #,m 3,m 0#%'A,m !-,m 3,m *2m .0- '*'""m ^4*-0mL_m"#m13+'0m!-,$-0+!'A,m"#m&))*m^'%30mJYIZm"#2**"-m#,m$-,"-m4#0"#_Ym-1m &))*-m1-,m%'0-1m#,m*m#1203!230m1#!3,"0'm"#m*m.0-2#>,m7m.-0m*-m2,2-m"#$',#,m#,m %0,m+#"'"m*m#1203!230m2#0!'0'm7m!32#0,0'Ym1m.-0m#**-m/3#m+ -1m+32,2#1m .-"0>,m .0-"3!'0m 3,m !+ '-m #1203!230*m "#m *m .0-2#>,Ym 12m !-+.0!'A,m ,-m !-',!'"#m "#*m 2-"-m !-,m *-1m 4*-0#1m - 2#,'"-1m !-,m #*m m .3#12-m /3#m m *m .0'+#0m +32!'A,m *#m 1'%,m 3,m 4*-0m "#m FZGFm 7m #,m !+ '-m #*m m *#m !-,$'#0#m 3,m 4*-0m #*#4"-m #,m !3,2-m m 13m .0- '*'""m #1203!230*Ym ,m !3*/3'#0m !1-m + -1m 0#13*2"-1m 1-,m !-+.*#+#,20'-1m .3#12-m /3#m !"m .0-%0+m 31m 3,1m +20'!#1m "'12',21m7m1#m 1,m#,m"'12',2-1m.09+#20-1m','!'*#1Ym m m m m GLLm .)-OO&-O'/.#)(-O#(.# #-O SeqAA prH prE prL SUBsec #-/-#9(m MVVEDSMKATSAEDLSNSIANQNPRGRGGDEDEELEEGEIVGDDDLDSSNLSASLVHQPH 000011111111112344444444322111111111111222211111221111111221 000000011111000000000000111111111233333333321111111122223333 988877777677776654554444556667776554554444456666666666655444 LLLLLLLLLLLLLLL...........LLLLLLL...........LLLLLLLL........ SeqAA PLEHSWTFWFDNPSAKSKQATWGASIRPIYTFSTVEEFWSVYNNIHHPSKLAMRADLYCF prH 212211222222222221111100112211111112222222111112211100101011 prE 221111222211000000123443210111123334444333322111135676665543 prL 556666544556666677765445676667655443333444566666543212223344 SUBsec....LL......LLLLLLL.....LLLLLLL.............LLL.....EEE..... SeqAA KHKIEPKWEDPVCANGGKWTVNFPRGKSDNGWLYTLLAMIGEQFDCGDEICGAVVNVRSG prH 112222212222211111122221222222122222222111111111112111111112 prE 322233343332211123333323333333332222333333211111232333344311 prL 555444444444566655444444444444444444333445667677654444433566 SUBsec.............LLL...........................LLLLL..........LL SeqAA prH prE prL SUBsec QDKISIWTKNASNEAAQASIGKQWKEFLDYNESIGFIFHDDAKKFDRHAKNKYMV 1111111111222233222233334322112211111112357666553311100 1111223332111112343212112333222222355431000000000000100 7776665445665654433444543334555455433356542323346678789 LLLL...................................L..H.......LLLLL T (&30 TEMD[m /.*/.O"#*m .0-%0+m m !-,m *m 1#!3#,!'m .0-2#'!m "#*m %#,m #Jm "#m //'#-O'&)m 7m *-1m +32,2#1m #,!-,20"-1m +0!"-1m #,m 0-(-m ^.- *!'A,m _m 7m #,m 4#0"#m ^.- *!'A,m _Ym 1m *>,#1m ',$#0'-0#1m!-00#1.-,"#,mm*1m.0- '*'""#1m.0m!"m+',-9!'"-m"#m!-,20' 3'0m#,m3,m!-,$-0+!'A,m 1#!3,"0'Ym.0[m.0- '*'""m"#m&<*'!#Zm.0[m.0- '*'""m"#m!"#,m*0%m7m.0[m.0- '*'""m"#O&))*Ym ',*+#,2#Zm *m B*2'+m *>,#m ^1#!_m !-00#1.-,"#m m *m .0#"'!!'A,m "#m #1203!230m 1#!3,"0'm #,m !"m +',-9!'"-m1#%B,m*1m.0- '*'""#1m,2#0'-0#1Zm"-,"#m[m&<*'!#Zm[m*))*m7m[m!"#,m*0%YmbYcm1'%,'$'!m /3#m,-m1#m.3#"#m1'%,0m3,m#1203!230m.-0/3<m*m.0- '*'""m"#m!"m!-,$-0+!'A,m2'#,#m.3,23!'A,m '%3*m-m+#,-0m"#mKYm m 0!'1m m *1m .0#"'!!'A,m "#m *m #1203!230m Im "#m *m .0-2#>,m #Jm 7m m 13m +-"#*(#m +#"',2#m #*m .0-%0+m 7-*m 1#m &,m .-"'"-m ,*'80m *%3,1m "#m *1m +32!'-,#1m "#2#!2"1m !-,m +7-0m "#2**#Ym *m #123"'-m #,m #*m +32,2#m Hm ^$+'*'m KM_m ,-1m &m .#0+'2'"-m- 1#040m/3#m#*m!+ '-m*3GHO71m.-"0>m$#!20m#,m*m',2#0!!'A,m!-,m#*m 131202-m^*m+-*<!3*m*m"#*m+_Ym#!-0"#+-1m/3#m2091m*m',$#!!'A,m4'0*Zm1'm*m ',2#0!!'A,m #,20#m *m .0-2#>,m #Jm 7m #*m +m "#*m 4'031m ,-m 1#m .0-"3!#m !-00#!2+#,2#Zm#*m4'031m,-m.-"09m',$#!20m*m.*,2Ym,m#12#m+32,2#m*m1312'23!'A,m#1m "#m 3,m +',-9!'"-m !0%"-m ,#%2'4+#,2#m ^9!'"-m %*329+'!-_m m -20-m !0%"-m .-1'2'4+#,2#m^*'1',_Ym12#m!+ '-m.-"0>m.0-4-!0m*m"#1.0'!'A,m-m.0'!'A,m"#m ,3#4-1m #,*!#1m -!1'-,,"-m 3,m 3,'A,m +91m "< '*m #,20#m #*m ','!'-m "#*m +m 7m #*m !#,20-m!2'4-m-m"#m3,'A,m"#m#JYm-0m#12#m+-2'4-Zm.-"0>m20201#m"#m3,m+32,2#m +#,-1m#$'!'#,2#m#,m*m',2#0!!'A,m.0-2#>,j131202-Ym"#+91Zm#*m4*-0m"#mm.0m GLMm #-/-#9( .)-OO&-O'/.#)(-O#(.# #- #12m+32!'A,m#1m"#mFYFFZm7m.-0m*-m2,2-m!-,$'0+m#*m.-1' *#m#$#!2-m"#m*m+32!'A,m#,m *m$3,!'-,*'""m"#m*m.0-2#>,Ym *m+'1+-m!+ '-m.#0-m#,m-20m.-1'!'A,m1#m&m.0-"3!'"-m#,m#*m+32,2#mKm^$+'*'mKI_m /3#m 1312'237#m 2+ '<,m #*m 9!'"-m %*329+'!-m .-0m *m *'1',Ym *m 9!'"-m %*329+'!-m #,m #*m %#,-2'.-m 1'*4#120#m !0#m 3,m #,*!#m "#m &'"0A%#,-m !-,m *m 1#0',m OIYm 12#m #,*!#m +,2'#,#m .0- *#+#,2#m *m &<*'!#m *$m 7m *m &-(m #2m 3,'"1m ","-m #12 '*'""m 7m !'#02m0'%'"#8mm+ 1m!-,$-0+!'-,#1Ym,m!+ '-Zm*m*'1',m/3#m!-,2'#,#m#*m+32,2#m ,-m.3#"#m#12 *#!#0m#12#m#,*!#m.3#12-m/3#m13m0"'!*m#129m!0%"-m.-1'2'4+#,2#m7m ,-m ,#%2'4+#,2#m !-+-m #*m 0"'!*m "#*m 9!'"-m %*329+'!-Ym m $*2m "#m #12#m #,*!#m .-"0>m .0-.-0!'-,0m +91m $*#6' '*'""m #,m #12m 8-,m "#m *m +-*<!3*m !-,m !-,1#!3#,!'1m '+.0#"#!' *#1Ym 12m 1312'23!'A,m .0-.-0!'-,m +#,-0m 0'%'"#8m m #12m .02#m #1203!230*m 7m #,m !-,1#!3#,!'m +#,-0m #12 '*'""Zm "#+91Zm #*m 4*-0m "#m m .0m#12m+32!'A,m#1m"#mFYFHYm #"',2#m*m.0#"'!!'A,m#,mIm1#m&m.-"'"-m- 1#040m/3#m*m+32!'A,m"#*m+32,2#mNm ^$+'*'m GHHO_m .09!2'!+#,2#m ,-m .0-4-!0>m !+ '-1m #1203!230*#1Ym *m !+ '-m "#m *,',m m 4*',m ,-m *2#0m *m #1203!230m .3#12-m /3#m + -1m 1-,m +',-9!'"-1m ,-m .-*0#1m7m!-,m3,m0"'!*m+37m.#/3#@-Ym*m4*-0m"#mm2+ '<,m!-,$'0+m#12#m"2-m "9,"-*#m 3,m .3,23!'A,m "#m FYGFYm ',m #+ 0%-Zm 7m !-+-m 1#m &m !-+#,2"-m ,2#0'-0+#,2#Zm #12#m 0#13*2"-m #1m !-,20"'!2-0'-m *m 0#13*2"-m - 2#,'"-m +#"',2#m Ym12-m#1m"# '"-mm/3#m+ -1m.0-%0+1m1#m 1,m#,m"'12',2-1m.09+#20-1Ym,m #12#m !1-Zm *-m !-,4#,'#,2#m 1#0>m 2#,#0m #,m !3#,2m + -1m 0#13*2"-1m 7m .-0m *-m 2,2-m !-,1'"#00m /3#m *m +32!'A,m "#m *m $+'*'m GHHOm .3#"#m $#!20m m *m #1203!230m 1#!3,"0'm7m/3'891mm*m$3,!'-,*'""m"#m*m.0-2#>,Ym ',*+#,2#Zm*m+32!'A,m"#*m+32,2#mOm^$+'*'mJJJ_Zm1#%B,m#*m+-"#*-mIZm,-m.0#!#m /3#m.0-4-/3#m3,m!+ '-mm,'4#*m"#m%'0-m#,m*m#1203!230m1#!3,"0'm"#m*m.0-2#>,Ym ',m#+ 0%-Zm#*m!+ '-m"#m%*'!',mm9!'"-m%*329+'!-m',20-"3!#m3,m!0%m,#%2'4m7m 3,m 0"'!*m +3!&-m +7-0Ym #,'#,"-m #,m !3#,2m *m .-1'!'A,m ',2#0,m "#m #12#m +',-9!'"-m7m*m',20-"3!!'A,m"#m*m!0%m,#%2'4Zm#12m+32!'A,m.-"0>m$#!20m#,m *1m',2#0!!'-,#1m!-,m*-1m*'%,"-1m"#m*m.0-2#>,m#JYm#%B,m#*m,9*'1'1m!-,mm *m+32!'A,m/3#m!-,2'#,#m#12m$+'*'m#,m*m.-1'!'A,mGILm"#m*m1#!3#,!'m.0-2#'!m#1m 3,m 0#%'A,m !-,m 3,m *2m .0- '*'""m ^4*-0m L_m "#m 13+'0m !-,$-0+!'A,m "#m &))*O -m %'0-Em ,m#*m.0-2-!-*-m"#mZmm.02#m"#m*m"#2#!!'A,m#m'"#,2'$'!!'A,m"#m+32,2#1Zm1#m "# #m0#*'80m#*m#123"'-m"#m1#%0#%!'A,m"#m*m+32!'A,m7m"#m13m$#,-2'.-Ym0m#*m%#,m GLNm .)-OO&-O'/.#)(-O#(.# #-O #-/-#9(m m.3"-m0#*'801#m#12#m#123"'-m""-m/3#m#*m,9*'1'1m$#,-2>.'!-m,-m0#/3#0>m+3!&-m 20 (-Zm 2029,"-1#m "#m - 1#040m 1A*-m #*m !0#!'+'#,2-m "#m *m .*,2m 7m 13m #12"-m "#m .'%+#,2!'A,Ym 0m #*m 0#12-m "#m *-1m %#,#1m ,*'8"-1m #,m #12#m 20 (-m ^>Fm I#-)J>_m#*m#123"'-m$#,-2>.'!-m2-"4>m/3#"m.#,"'#,2#m.-0m0#/3#0'0m+91m2'#+.-m7m 0#!301-1Ym',m#+ 0%-Zm.0m#*m%#,m#Jm1#m&'8-m*m0#!-*#!!'A,m"#m*1m1#+'**1mHm7m *m - 2#,!'A,m "#m *1m 1#+'**1m Im .0m .-"#0m $'(0m *m +32!'A,m .0Zm #,m 3,m $3230-Zm .-"#0m!-,$'0+0m#*m#$#!2-m$#,-2>.'!-m+#"',2#m',-!3*!'A,m!-,m3,m 2#0>m"#m4'031m ^ *mJYI_Ymm !+ TEMD[m#13*2"-1m"#*m#123"'-m"#m1#%0#%!'A,m"#m*1m$+'*'1m+32,2#1m"#*m%#,m#Jm#,!-,20"-1m#,m *m.- *!'A,mYg[m'*"m27.#m-m1'*4#120#Zm[m-+-!'%-2-Zm[m32,2#Ym m Amplicón Exón Posición cambio AA Familia M2 Plantas secuenciadas en M2 Segregación en M2 (WT/H/M)* eIF4E-1 Exón 1 G74A Arg25Lys F2036 24 9/7/8 eIF4E-2 Exón 2 G385A Glu129Lys F57 8 5/3/0 m ,m4#8m'"#,2'$'!"1m*1m$+'*'1m+32,2#1m#,m#*m%#,m>m"#m*m.- *!'A,mm1#m !0#!'Am *m %#,#0!'A,m HYm 0m *m $+'*'m HFILm 1#m .3"'#0-,m !0#!#0m 7m 1#!3#,!'0m HJm .*,21Zm+'#,201m/3#m.0m*m$+'*'mKMm1A*-m1#m- 234'#0-,m-!&-m"# '"-mm3,m (m 21m"#m%#0+',!'A,Ym0!'1mm*m1#!3#,!'!'A,m"#*m$0%+#,2-m"#*m%#,m,*'8"-m1#m .3"'#0-,m- 2#,#0m*-1m"2-1m"#m1#%0#%!'A,m/3#m.0#!#,m#,m*m *mJYIYmm 1m0#*#4,2#m#*m&#!&-m"#m/3#m.0m*m$+'*'mKMm,-m1#m- 234-m,',%B,m&-+-!'%-2-m +32,2#Ym 12#m 0#13*2"-m .-"0>m #120m 0#*!'-,"-m !-,m #*m &#!&-m "#m /3#m *m +32!'A,m #,m &-+-!'%-1'1m !-,"'!'-,#m #*m !-00#!2-m !0#!'+'#,2-m "#m *m .*,2m -m 13m %#0+',!'A,Ym m +32!'A,m #,m #12m $+'*'m 2'#,#m 3,m 4*-0m #,m m "#m FYFFm 7m .-0m *-m 2,2-m *m +32!'A,m $#!20>m m *m $3,!'-,*'""m "#m *m .0-2#>,Zm !-+-m 7m 1#m &m !-+#,2"-m ,2#0'-0+#,2#Ym ,m#*m!1-m"#m*m$+'*'mHFILm*m1#%0#%!'A,m$3#m"#m,3#4#m1'*4#120#1m&-+-!'%-2-1Zm 1'#2#m &#2#0-!'%-2-1m 7m -!&-m &-+-!'%-2-1m +32,2#1Ym -1m &-+-!'%-2-1m +32,2#1m 1#m .-"0>,m $#,-2'.0m .0m !-,-!#0m 7m 1 #0m "#m /3<m +-"-m $#!2m #12m +32!'A,m m *m $3,!'-,*'""m"#m*m.0-2#>,m7m1'm&,m"/3'0'"-m*%3,m0#1'12#,!'mm*%B,m4'031m/3#m ',$#!2m m *m .*,2m "#*m +#*A,Zm 1- 0#2-"-m .-2'4'031m !-+-m Zm m -m Zm #,20#m-20-1Ym m GLOm #-/-#9( .)-OO&-O'/.#)(-O#(.# #- EMCMDT"#!TT ,m#*m!1-m"#*m%#,mI#-)J>m1#m- 234-m3,m+32,2#m#,m*m.- *!'A,mYmm$+'*'m GKNMm 2'#,#m 3,m +32!'A,m /3#m .0-4-!m 3,m !+ '-m "#m +',-9!'"-m "#m 0%',',m m *'1',Ym *%3,-1m 20 (-1m 0#!'#,2#1m &,m 73""-m m #,2#,"#0m +#(-0m !39*m #1m *m "'$#0#,!'m"#m$3,!'-,*'""m#,20#m%#,#1m"#*m!-+.*#(-m"#m','!'!'A,m"#m*m20"3!!'A,m 7m 131m '1-$-0+1Ym ,m #(#+.*-m #1m #*m "#m >m 7m I#-)J>m #,m *-1m !3*#1m 1#m &m "#+-120"-m/3#m!"m3,-m.-1##m+7-0m$','""m.-0m*%B,m2'.-m"#m+m^',%01m 7m !-*YZm GOOO_Ym 20-1m #123"'-1m "#+3#120,m /3#m *-1m %#,#1m >m 7m I#-)J>m .3#"#,m #6.0#101#m "'$#0#,!'*+#,2#m #,m 1#%B,m /3#m 2#('"-1m 7m .#0'-"-1m "#m "#100-**-m "#m *m .*,2Ym'#,201m/3#m#,m,#)*-#-m1#m!-+.0- Am/3#m+ -1m%#,#1m1-,m#6.0#1"-1m .-0m'%3*m#,m2#('"-1m+#0'12#+92'!-1m7m#,m!<*3*1m#,m.#0>-"-m"#m"'4'1'A,m"#mA0%,-1m ',+"30-1Zm1#m#6.0#1,m#,m"'12',2m.0-.-0!'A,m#,m2#('"-m+"30-m^-"0'%3#8m7m!-*YZm GOON_Ym 0#!#m /3#m *1m 0#1'12#,!'1m m 4'031m "#1!0'21m &12m &-0m ',"'!,m /3#m !"m 4'031m 2'#,#m 3,m !'#02m #1.#!'$'""m !-,m 3,-m "#m *-1m "-1m %#,#1m 7m 2+ '<,m #12m #1.#!'$'!'""m.0#!#m40'0m#,m$3,!'A,m"#m*m#1.#!'#m"#m.*,2Ym*mm^))O."O 0#,/-_m',2#0!!'-,m!-,m#*m%#,m>m#,m2-+2#Zm*#!&3%m7m.'+'#,2-m+'#,201m/3#m#,m ,#)*-#-m',2#0!!'-,m!-,m13m'1-$-0+m^#**'1m7m!-*YZmHFGH_Ym 1m.-0m#**-m/3#m2,2-m#*m%#,mI#-)J>m!-+-m#*m>m"# #,m2#,#01#m#,m!3#,2m#,m*m B1/3#"m "#m .-1' *#1m ,3#41m 0#1'12#,!'1m 0#!#1'41Ym "#+91Zm #6'12#,m !1-1m #,m *-1m /3#m 1A*-m #*m %#,m I#-)J>m #1m #*m 0#1.-,1 *#m "#m !-,$#0'0m *m 0#1'12#,!'m m 3,m 4'031Ym #!'#,2#+#,2#m 1#m &m "#+-120"-m /3#m #*m 4'031m m ^&/'O *)2O 0#,/-_m 1A*-m ',2#0!!'-,m !-,m #*m %#,m I#-)J>m +'#,201m /3#m ,-m *-m &!#m !-,m #*m %#,m >Ym ,m #*m 1'*#,!'+'#,2-m "#*m %#,m I#-)J>m #,m .*,21m "#m ,/(/-FO <121O 1#m +-1200-,m 0#1'12#,2#1m$0#,2#mm*m',$#!!'A,m!-,m#*m4'031mm+'#,201m/3#m#,m#*m1'*#,!'+'#,2-m "#*m %#,m >m ,-m 1#m - 234-m 0#1'12#,!'Ym "#+91Zm 1#m !-+.0- Am *m #1.#!'$'!'""m "#m ',2#0!!'A,m #,20#m #*m .%m "#*m 4'031m 7m #*m %#,m I#-)J>m +#"',2#m #,17-m "#m "- *#m &> 0'"-Zm!-00- -0,"-m#*m+'1+-m0#13*2"-m^,%m7m!-*YZmHFGI_Ym ,m +#*A,m #6'12#,m #123"'-1m /3#m !-,$'0+,m /3#m #*m 1'*#,!'+'#,2-m "#*m %#,m >m .-02m 0#1'12#,!'m $0#,2#m *%3,-1m 4'031Ym 91m !-,!0#2+#,2#m #*m #6.#0'+#,2-m 0#*'8"-m.-0m-"0>%3#8j#0,9,"#8m7m!-*YZmHFGHm"#+-120Am/3#m#*m1'*#,!'+'#,2-m"#m #12#m%#,m!-,$#0>m0#1'12#,!'mm!320-m^ZmZmZm_m"#m*-1m-!&-m 4'031m!-,m*-1m/3#m',$#!20-,m*1m.*,21m"#m+#*A,Ym',m#+ 0%-Zm,-m1#m!-+.0- Am#*m 1'*#,!'+'#,2-m"#*m%#,mI#-)J>m7m.-0m*-m2,2-m,-m1#m.3#"#m1 #0m1'm#12#m!-,$#0'0>m 0#1'12#,!'m.0m*%3,-1m"#m#12-1m4'031Ymm GMFm .)-OO&-O'/.#)(-O#(.# #-O #-/-#9(m m .#10m "#m /3#m #*m +32,2#m "#2#!2"-m #,m #12#m 20 (-m !-,2'#,#m 3,m !+ '-m "#m +',-9!'"-m!-,m3,m4*-0mGYFFm#,mm&#+-1m/3#0'"-m4*-00m*m'+.-02,!'m"#m*m 0#%'A,m"-,"#m1#m#,!3#,20m#,m$3,!'A,m"#m*m&-+-*-%>m/3#m2'#,#,m#*m%#,m#Jm7m13m '1-$-0+m^'%30mJYJ_Ymm#m&m- 1#04"-m/3#m*m+32!'A,m#129m*-!*'8"m#,m3,m8-,m "-,"#m-201m#1.#!'#1m2'#,#,m+32!'-,#1m#,m#*m%#,m>m/3#m!-,$'#0#,m0#1'12#,!'1mm *%3,-1m 4'031m ^'%301m JYHm 7m JYJ_Ym *m !+ '-m 0%JI71m 1#m .-1'!'-,m #,m *m 8-,m !-*-0#"m #,m $3!1'm ^'%301m JYHm 7m JYJ_m 7m "-,"#m 1#%B,m - %*'m 7m 0,2Zm #6'12#m +91m !3+3*!'A,m "#m !+ '-1m "#m +',-9!'"-1m #,m #*m %#,m #Jm /3#m !-,$'#0#,m 0#1'12#,!'m,230*mm4'031Ym*m+'1+-m2'#+.-Zm#1m3,m0#%'A,m+91m#6.3#12m*m#62#0'-0m 1#%B,m*m!-,$'%30!'A,m#,mIm"#m*m.0-2#>,m^- %*'m7m0,2ZmHFFL_Ym-0m*-m2,2-Zm 7m 2#,'#,"-m 1- 0#2-"-m #,m !3#,2m *m &-+-*-%>m #,20#m + -1m %#,#1Zm #12#m +32,2#m "# #0>m 2#1201#m *m '%3*m /3#m *-1m "#2#!2"-1m #,m #*m %#,m #Jm #m ',$#!201#m !-,m *m +'1+m 2#0'm"#m4'031m.0m!-+.0- 0m1'm*m+32!'A,m.0-.-0!'-,m-m,-m0#1'12#,!'m m*%B,m4'031Ym m (&30 TEMEMm*',#+'#,2-m+#"',2#m*312*m#,20#m*m1#!3#,!'m.0-2#'!m"#m*-1m%#,#1m>m7mI#-)J>Ym ,m $3!1'm *m 8-,m "#1!0'2m .-0m - %*'m 7m 0,2m /3#m !-,2'#,#m +91m !3+3*!'A,m "#m !+ '-1m +',-!>"'!-1m/3#m!-,$'#0#,m0#1'12#,!'mm4'031m#,m"'12',21m#1.#!'#1m^'%30mJYH_m7m#,m0-(-m#*m!+ '-m"#m +',-9!'"-m/3#m.0-4-!m*m+32!'A,m"#2#!2"m+#"',2#mm#,m*m$+'*'mGKNMm"#m*m.- *!'A,m m.0mI#-)J>Ymm m EMCMET $PTTTQT 0m #*m %#,m ;m ,-m 1#m #,!-,20Am ,',%B,m +32,2#m #,m *m .- *!'A,m m 7m ,-m 1#m .3"-m&!#0m#*m,9*'1'1m#,m*m.- *!'A,mYmm0#%'A,m,*'8"m#0m0#*2'4+#,2#m .#/3#@m^LGKm. _m7m!-,m3,m.0-.-0!'A,m"#mm"#*mJJPYm-1m!# "-0#1m!-,m*-1m/3#m 1#m ,*'80-,m *1m .- *!'-,#1m $3#0-,m "'1#@"-1m m .02'0m "#m *m 1#!3#,!'m "#m *m 40'#""m LHjGGIZm #12#m .-"0>m 1#0m #*m +-2'4-m .-0m #*m !3*m *m &!#0m #*m ,9*'1'1m #,m *m GMGm #-/-#9( .)-OO&-O'/.#)(-O#(.# #- 40'#""m&0-,-m"#m*m.- *!'A,mm*-1m!# "-0#1m,-m$3#0-,m13$'!'#,2#+#,2#m #1.#!>$'!-1Ym 0- *#+#,2#m *-1m !# "-0#1m "'1#@"-1m ,-m +.*'$'!,m #1m 0#%'A,m .-0/3<m *m 0#%'A,m !-+.*#+#,20'm ,-m #6'12#m -m !-,2'#,#m "#+1'"-1m .-*'+-0$'1+-1m 0#1.#!2-mm*m0#%'A,m-0'%',*m"#mLHjGGIYm-0m#**-m1#m"#!'"'Am,-m1#%3'0m"#*,2#m!-,m #*m,9*'1'1m"#m#12#m%#,m#,m*m.- *!'A,mYm T EMCMFTTT -,m*-1m0#13*2"-1m- 2#,'"-1m#,m#12#m20 (-m/3#"m.#,"'#,2#m*m$'(!'A,m"#m*%3,-1m "#m*-1m+32,2#1m#,m&-+-!'%-1'1m7m*m- 2#,!'A,m"#m13$'!'#,2#m1#+'**m"#m*-1m+'1+-1Zm .0m.-"#0m&!#0m*-1m#6.#0'+#,2-1m"#m$#,-2'."-m"#!3"-1m.0m!"m%#,Ymm + '<,m #1m ',"'1.#,1 *#m - 2#,#0m #*m +32,2#m '1*"-m "#m -201m +32!'-,#1Zm .3#12-m /3#m 3,m "#m *1m "#14#,2(1m "#*m m #1m /3#m *1m .*,21m 1#*#!!'-,"1m ,-m 1A*-m !-,2'#,#,m*m+32!'A,m"#m',2#0<1m1',-m2+ '<,m+3!&1m-201m/3#m.-"0>,m$#!20m*m $#,-2'.-m#,m#123"'-Ym ,m#12#m20 (-m#12m* -0m"# #0>m&!#01#m!-,m*-1m+32,2#1m- 2#,'"-1m"#*m%#,m#Jm ^HFILm 7m 1#m &m $'("-m 7m $*20>m $'(0m *1m $+'*'1m GHHOZm HFLFZm JJJZm KMm 7m KI_Ym m !-,2',3!'A,m1#m"# #0>,m',$#!20m!-,m3,m 2#0>m"#m4'031m.0m.-"#0m!-+.0- 0m1'm *%3,m "#m *1m +32!'-,#1m !-,$'#0#m 0#1'12#,!'m m *m .*,2Ym ',m #+ 0%-Zm #1m .-1' *#m /3#m .0m *%B,m +32,2#m ,-m 1#m .-1' *#m - 2#,#0m #*m &-+-!'%-2-Ym ,m #*m !1-m "#m *m $+'*'m KMm 7m 1#m &m ',2#,2"-m 40'1m 4#!#1m m .02'0m "#m *m 32-$#!3,"!'A,m "#m 3,m &#2#0-!'%-2-mHm7m,-m&m1'"-m.-1' *#Ymm #1.#!2-mm*m 2#0>m"#m4'031m!-,m*m!3*m"# #0>,m',$#!201#m*-1m+32,2#1Zm7m#6'12#m 3,m #123"'-m 0#!'#,2#m ^-"0>%3#8k#0,9,"#8m 7m !-*YZm HFGH_m /3#m &m "#+-120"-m !-+-m +#"',2#m #*m 1'*#,!'+'#,2-m ^'_m "#*m +m "#m +j#Jm *1m .*,21m "#m +#*A,m 20,1$-0+"1m 0#13*2 ,m 0#1'12#,2#1m m Jm 4'031m "'12',2-1m ^//',O 0#(O 3&&)1#(!O 0#,/-O^_Zm&)(O(,).#O-*).O0#,/-O^_Zm/"#(#O3&&)1O')-#O0#,/-O^_m 7m ),)(O 1.,'&)(O ')-#O 0#,/-m ^__Ym 30,2#m #12#m 20 (-m 1#m .0- 0-,m 2+ '<,m -20-1m 4'031Zm !-+-m //',O ')-#O 0#,/-O ^_m ^%<,#0-m //')0#,/-_Zm .,'&)(O')-#O0#,/-O^_m^%<,#0-m).30#,#JFO//,#.O3&&)1O-./(.#(!O#-),,O 0#,/-O ^_m ^%<,#0-m ,#'#0#,/-_Zm //,#.O *"#N),(O 3&&)1-O 0#,/-m ^_m ^%<,#0-m )&,)0#,/-_Zm *3O ,#(!-*).O 0#,/-m ^_m ^%<,#0-m ).30#,#_m 7m .O *-/)3&&)1-O 0#,/-m ^_m ^%<,#0-m &)-.,)0#,#_Zm .#0-m #,m #12-1m !1-1m #*m 1'*#,!'+'#,2-m"#m#Jm,-m!-,$'0'Am0#1'12#,!'m^-"0>%3#8k#0,9,"#8m7m!-*YZmHFGH_Ymm 0!'1m m *-1m 0#13*2"-1m .0#1#,2"-1m #,m #12#m 20 (-m 1#m &,m .-"'"-m "#2#0+',0m *1m !-,"'!'-,#1m.0m"#100-**0m.-12#0'-0#1m.*2$-0+1m"#mZm3,m#(#+.*-m#1m*m GMHm .)-OO&-O'/.#)(-O#(.# #-O #-/-#9(m "#100-**"m .-0m *m #+.0#1m '#&&-O #.9m (3,2+#,2#m !-,m #*m jm #,m #*m +0!-m "#*m .0-7#!2-m Ym *m 7m !-+-m 1#m &m !-+#,2"-m ,2#0'-0+#,2#Zm #12m.*2$-0+m1#m&m"#100-**"-mm.02'0m"#m3,m*>,#m.30m"#m+#*A,m2'.-me'#*m"#m .-eYm #m &,m +32"-m *1m 1#+'**1m !-,m 3,m .-0!#,2(#m "#m GZKPm "#m m 7m 1#m &,m - 2#,'"-m .0-6'+"+#,2#m IGFFm ',"'4'"3-1m Hm ^#,m #*m +-+#,2-m "#m #1!0' '0m #12m 2#1'1_Zm #,m *-1m !3*#1m 7m 1#m &,m "#2#!2"-m Nm +32,2#1m #,m #*m %#,m >m 7m Im #,m #*m %#,m I#-)J>Ym#m*-1mNm+32,2#1m#,m#*m%#,m#JZmLm2'#,#,m*m+32!'A,m#,m0#%'A,m#6A,'!m +'#,201m /3#m Hm #,m 0#%'A,m ',20A,'!Ym #m *-1m +32,2#1m #6A,'!-1Zm Hm 2'#,#,m 3,m 4*-0m m +#,-0m "#m FYFKm 7m .-0m *-m 2,2-m ,-m 1#0>,m 2-*#0"-1Ym 0m #*m %#,m I#-)J>Zm #*m ,B+#0-m"#m+32,2#1m#,!-,20"-1m1'%3#m1'#,"-m+3!&-m+#,-0m7m"#m*-1m20#1m+32,2#1m "#2#!2"-1m 1A*-m 3,-m 1#m *-!*'8m #,m 0#%'A,m #6A,'!m !-,m 4*-0m FYFHm #,m Ym 12m .0-.-0!'A,m!-,$'0+0>m*m&'.A2#1'1m"#m/3#m#^'1-_Jm#1m+91m',"'1.#,1 *#m.0m*m !<*3*m^,%m7m!-*YZmHFGI_Ym -"-1m#12-1m+32,2#1Zm(3,2+#,2#m!-,m*-1m- 2#,'"-1m#,m#12m2#1'1m1#09,m#,m3,m$3230-m ',$#!2"-1m!-,m*%3,-1m"#m*-1m4'031m+#,!'-,"-1m,2#0'-0+#,2#m7m"#m#12#m+-"-m1#m .0- 09m1'm*m+32!'A,m/3#m&m"/3'0'"-m!"m3,-m!-,$'#0#m *%3,m0#1'12#,!'mm*m .*,2Zm"#m+-"-m/3#m.3"'#0m1#0m32'*'8 *#m#,m.0-%0+1m"#m+#(-0m%#,<2'!m"#m*m #1.#!'#Ym # #m 2#,#01#m #,m !3#,2m /3#m .0m .-"#0m !-+#0!'*'80m ,3#41m *>,#1m - 2#,'"1m m .02'0m"#m*m+#(-0m%#,<2'!Zm*m2#!,-*-%>mm32'*'80m#,m30-.m#,m#12-1m+-+#,2-1m ,-m .3#"#m 1#0m *m 20,1$-0+!'A,m %#,<2'!Ym -0m #(#+.*-Zm *m 2#!,-*-%>m 'm ,-m 1#m .-"0>m 32'*'80m #,m .0-"3!2-1m !-+#0!'*#1Zm #,m !+ '-Zm *m 2<!,'!m "#m m ,-m .0#1#,2m#12m*'+'2!'A,m7m/3#m1#m- 2'#,#,m,3#41m*>,#1m+#"',2#m3,m2#!,-*-%>m /3#m,-m#+.*#m20,1%#,#1'1Ymm T m $ GMIm #-/-#9( ) m m EMDT".T m *m !-m -$0#!#m *m .-1' '*'""m "#m '"#,2'$'!0m #$'!'#,2#+#,2#m +32!'-,#1m ,230*#1m #,m *1m 40'#""#1m ,*'8"1Ym -0m #**-m 0#13*2m +37m ',2#0#1,2#m ,*'80m "'12',2-m%#0+-.*1+m.0m*m"#2#!!'A,m"#m&.*-2'.-1m.0#1#,2#1m#,m*m,230*#8m7m /3#m .3#",m .-020m 40' '*'""m ,230*m #m ',$-0+!'A,m $3,!'-,*m #,m %#,#1m "#m ',2#0<1Ym ,m #*m +0!-m "#*m .0-7#!2-m m 1#m "#!'"'Am &!#0m #*m ,9*'1'1m "#m !-m #,m *-1m %#,#1m 7m ,*'8"-1m +#"',2#m Ym ,m #12m 2#1'1m 1#m &m 0#*'8"-m#*m,9*'1'1m"#m*-1m%#,#1m>m7m;m7m#,m#*mm1#m0#*'8Am#*m,9*'1'1m #,m*-1m%#,#1mI#-)J>m7mYm *m ,9*'1'1m 1#m 0#*'8Am !-+.0,"-m *m +'1+m 40'#""m !-,m *m /3#m 1#m & >m "#100-**"-m*m.- *!'A,m"#mm^LHjGGI_m7mGGIm!!#1'-,#1m.0-.-0!'-,"1m .-0m#*m ,!-m"#m%#0+-.*1+m"#*mYm1mGGIm!!#1'-,#1m#129,m!0!2#0'8"1m .0m!'#02-1m!0!2#0#1Zm#,20#m#**-1m!0!2#0#1m"#m$032-m!-+-m#*m!-*-0m"#m*m.3*.Zm#*m 0-+m 7Zm "#m *%3,1m "#m #**1Zm 1#m "'1.-,#m "#m '+9%#,#1m "#*m $032-m ^#12m ',$-0+!'A,m #129m "'1.-,' *#m #,m #*m _Ym ',m #+ 0%-Zm "#1$-023,"+#,2#m ,-m #129,m !0!2#0'8"1m.0m0#1'12#,!'mm.2A%#,-1Ym-0m#**-Zm#*m,9*'1'1m"#m!-m!-,m #*m %#,m #Jm %#,#0m 3,m .0'+#0m !0' "-m .0m 1#*#!!'-,0m /3#**1m 40'#""#1m /3#m .3"'#0,m2#,#0m3,m&.*-2'.-m/3#m!-,$'0'#0m0#1'12#,!'mm.-2'4'031m7m#,m3,m1#%3,"m #2.Zm1#m"# #0>,m4*-00m$#,-2>.'!+#,2#m*1m!!#1'-,#1m"#m',2#0<1Ym -,m#*m,9*'1'1m"#*m%#,m;m1#m.0#2#,">m0#*!'-,0m*%B,m&.*-2'.-m"#2#!2"-m!-,m *%B,m !09!2#0m "#m +"30!'A,m "#m $032-m 2#,'#,"-m #,m !3#,2m /3#m *m 40'#""m "#m 0#$#0#,!'mLHjGGIm#1m3,m40'#""m,-m!*'+2<0'!Ym m EMDMBT$ETPTTTTTQT -+-m1#m&m!-+#,2"-mm*-m*0%-m"#m#12#m20 (-Zm1#m&m"#1!0'2-m/3#m#*m%#,m#Jm#1m 0#1.-,1 *#m"#m*%3,1m0#1'12#,!'1mm.-2'4'031m7mm-20-1m4'031Zm7m/3#m*m.0#1#,!'m "#m+32!'-,#1m#1.#!>$'!1m#,m#12#m%#,m.0-4-!,m/3#m#*m4'031m,-m.3#"m',2#0!!'-,0m !-,m #*m !-+.*#(-m "#m ','!'!'A,m "#m *m 20"3!!'A,m 7m .-0m *-m 2,2-Zm 20"3!'01#m !-+-m .0'+#0m .1-m "#m *m ',$#!!'A,m "#m *m .*,2Ym -0m #12#m +-2'4-m #,!-,200m 40' '*'""m ,230*m#,m#12#m%#,m.-"0>m'+.*'!0m'"#,2'$'!0m*%B,m,3#4-m&.*-2'.-m/3#m!-,$'0'#0m 0#1'12#,!'mm*%B,m4'031mm*m.*,2Ym GMJm )OO #-/-#9(m #m&,m'"#,2'$'!"-m3,m2-2*m"#mGHm.-*'+-0$'1+-1m#,m#*m,9*'1'1m"#m!-m!-,m #*m %#,m #JYm #m *-1m GHZm 1#'1m 1m 1#m #,!3#,20,m #,m 8-,1m #6A,'!1m 7m 3,-m #,m #*m Kdm m "#*m %#,Ym A*-m 3,-m "#m #**-1m .0-4-!m 3,m !+ '-m "#m +',-9!'"-m ^m GYKZm 1.MG*7_m^ *mJYJ_m!-,m3,m4*-0mFYFFm#,mm7m/3#m.-0m*-m2,2-Zm.-"0>m$#!20m #,m*m$3,!'-,*'""m"#m*m.0-2#>,Ymm m !+ TEME[m *m!-+.02'4m"#m*-1m.-*'+-0$'1+-1m"#2#!2"-1m.-0m!-m#,m#*m#123"'-m"#m'#2-m7m !-*Ym^HFFM_m7m*-1m'"#,2'$'!"-1m#,m#12#m20 (-Ymgm-1'!'A,m#,m*m1#!3#,!'m,3!*#-2>"'!m0#1.#2-m*mm!-"A,m"#m ','!'-m"#m*m20"3!!'A,m7m,3+#0!'A,m1'%,"m#,m#12#m20 (-Ym m 123"'-m 6A,igm GiNGm^GYH_m + '-m +',-9!'"-m '*#,!'-1-m !!#1'A,m #1'12#,!'m m4'031m m m m !-m m GiGHImm^GYI_m '*#,!'-1-m m GiGNLm^GYJ_m '*#,!'-1-m m m TFAFGACT -m&7m "2-1T BRCBCTPBMFQT !-m 1/HB+7T GiHJIm^GYL_m '*#,!'-1-m m m KiLOFm^HYK_m '*#,!'-1-m m m GiNGm^GYH_m '*#,!'-1-m m m GiGHImm^GYI_m '*#,!'-1-m m m GiGNLm^GYJ_m '*#,!'-1-m m m jFJLm m jGMNm m jKGHm m mGLGIMKm m m m '#2-m7m!-*YZm HFFMm FRGIDT $3CCI(1T KiLOFm^HYK_m '*#,!'-1-m m *m ,9*'1'1m +#"',2#m !-m "#*m %#,m #Jm #,m +#*A,m 7m 1#m & >m 0#*'8"-m ,2#0'-0+#,2#m ^'#2-m 7m !-*YZm HFFM_m !-,m #*m +#*A,m !*'+2<0'!-m #"0,2'1m !-+-m 0#$#0#,!'m 7m -201m GJMm 40'#""#1m "#m +#*A,m - 2#,'"1m "#m *m !-*#!!'A,m "#m %#0+-.*1+m"#m*m12!'A,m6.#0'+#,2*m"#mem7-0ejmm^9*%_Ym,m#12#m 20 (-m.0#4'-m1#m"#2#!20-,m!',!-m.-*'+-0$'1+-1Zm20#1m"#m#**-1m#,m#*m.0'+#0m#6A,m7m "-1m #,m #*m /3',2-m ^ *m JYJ_Ym -"-1m *-1m 1m /3#m 1#m "#2#!20-,m 0#13*20-,m 1#0m GMKm #-/-#9( ) 1'*#,!'-1-1m#6!#.2-m#*m!+ '-mLNIm"#*m/3',2-m#6A,m/3#m!-00#1.-,"#m*m!+ '-m"#m *#3!',m m &'12'"',m #,m *m .-1'!'A,m HHNm 7m #*m !39*m !-,$'#0#m 0#1'12#,!'m m m #,m m GLGIMKYm1m!!#1'-,#1m.0- "1m#,m#12#m20 (-m$3#0-,m1-+#2'"1mm#123"'-1m.0#4'-1m "#m 0#1'12#,!'m $0#,2#m m 3,m 2#0>m "#m 4'031m .3"'#,"-m '"#,2'$'!0m 40'#""#1m 0#1'12#,2#1m .0m *%3,-1m "#m #**-1Zm !-+-m *1m Jm !!#1'-,#1m 0#1'12#,2#1m m m ^',"'!"1m #,m *m *m JYJ_Ym -1m +.*'!-,#1m 32'*'8"-1m #,m + -1m 20 (-1m 1-,m *-1m +'1+-1Ym ,m*m'%30mJYJm1#m+3#120,m2-"-1m*-1m1m"#2#!2"-1m#,m#12#m20 (-m7m.-0m'#2-m7m !-*YZm^HFFM_m.0m#*m%#,m#JYm m _m _m GMLm T )OO T #-/-#9(m T (&30 T EMF[m _m 0"3!!'A,m m .0-2#>,m "#*m +m "#*m %#,m #JYm ,m 0-(-m 1#m 1#@*'8m #*m B*2'+-m !-"A,m "#m !"m#6A,m7m#,m4#0"#m#*m','!'-m"#m!"m#6A,Ym _m6-,#1m"#*m%#,m#Jm1#.0"-1m',"'!,"-m#*m2+@-m"#m !"m3,-m^#,m. _m7m*1m40'!'-,#1m#,!-,20"1[m#,m$3!1'm*1m"#2#!2"1m#,m#12#m20 (-m7m#,m#*m20 (-m"#m '#2-m7m!-*YZm^HFFM_Ym,m83*Zm#*mGHIm^mGYI_m7m#*mHGHm^mGYK_m"#2#!2"-1m#,m#12#m20 (-m.#0-m,-m #,m #*m "#m '#2-m 7m !-*YZm ^HFFM_Ym ,m %0'1Zm #*m m "#2#!2"-m #,m #*m 20 (-m "#m '#2-m 7m !-*Ym ^HFFM_m .#0-m ,-m "#2#!2"-m#,m#12#m20 (-Ym m 320-m "#m *-1m 1m "#2#!2"-1m #,m #12#m 20 (-m !-',!'"#,m !-,m *-1m /3#m $3#0-,m "#2#!2"-1m +#"',2#m !-m #,m #*m #123"'-m "#m '#2-m 7m !-*Ym HFFMm ^ *m JYJm 7m '%30m JYK Zm #,m $3!1'_Ym 12-m "#+3#120m /3#m "#,20-m "#m *m 40'#""m ,230*m #,!-,20+-1m *%3,-1m 1m !-,m +91m $0#!3#,!'m 7m .-0m *-m 2,2-Zm /3#m 1#m "#2#!2,m #,m "'12',2-m %#0+-.*1+Ym ,m !+ '-Zm -20-1m 1m 1#m .3#"#,m #,!-,200m !-,m +#,-0m $0#!3#,!'m !-+-m #1m #*m !1-m "#*m m GYIm ^GHI_m 7m #*m m GYKm ^HGH_m /3#m 1#m &,m "#2#!2"-m 1A*-m #,m #*m %#0+-.*1+m ,*'8"-m #,m #12#m 20 (-m 7m ,-m 1#m "#2#!20-,m #,m *1m40'#""#1m,*'8"1m#,m#*m#123"'-m"#m'#2-m#2m*Ym*mmGYKm#129m.0#1#,2#m1A*-m #,m *m 40'#""m m KFKLFHm ^ *m JYJ_m 7m .0-4-!m 3,m !+ '-m "#m 9!'"-m 1.902'!-m m %*'!',Ym 0m !-+.0- 0m 1'm #12#m m .0-4-!m *%3,m +-"'$'!!'A,m #,m *m !-,$-0+!'A,m "#m *m .0-2#>,m 7m #,m !-,1#!3#,!'Zm !-,$'#0#m 0#1'12#,!'m $0#,2#m *%B,m .2A%#,-m "# #0>m ',$#!201#m #12m 40'#""m ^ *m JYJ_m !-,m 3,m 2#0>m "#m 4'031Zm !-+-m7m1#m&m!-+#,2"-m,2#0'-0+#,2#Ym#m2-"-1m+-"-1Zm"# #m2#,#01#m#,m!3#,2m /3#m #12m 40'#""m .0#1#,2m #*m .-*'+-0$'1+-m #,m &#2#0-!'%-1'1m 7m "# #0>m .0'+#0-m $'(01#m*m+32!'A,Ymm -0m-20-m*"-Zm#*mm"#2#!2"-m#,m#*m20 (-m"#m'#2-m*-!*'8"-m#,m#*m#6A,mKm7m/3#m !-,$'#0#m 0#1'12#,!'m m m ,-m 1#m &m '"#,2'$'!"-m #,m ,',%3,m "#m *1m 40'#""#1m ,*'8"1m #,m #12#m 20 (-m ^ *m JYJ_Ym ,m #12#m !1-m #*m m 1#m .0#1#,2 m #,m &-+-!'%-1'1m#,m*1m40'#""#1m/3#m0#13*20-,m1#0m0#1'12#,2#1mmYm GMMm #-/-#9( ) ,m + -1m #123"'-1m #*m #6A,m /3#m .0#1#,2m +91m 40' '*'""m &m 1'"-m #*m .0'+#0-m +'#,201m/3#m#,m#*m1#%3,"-Zm2#0!#0-m7m!302-m,-m1#m&,m'"#,2'$'!"-m1m#,20#m*1m 40'#""#1m!-+.0"1Ymm m EMDMCT TPTTTBQT ,m #*m %#,m ;m 1#m &,m '"#,2'$'!"-m "-1m .-*'+-0$'1+-1m +#"',2#m *m 2<!,'!m "#*m !-m#,20#m*1mGGIm40'#""#1m,*'8"1m7m*m40'#""m"#m0#$#0#,!'mLHj GGIYm*mmG .0-4-!m3,m!+ '-m"#m+',-9!'"-m"#m*#3!',mm4*',m#,m*m.-1'!'A,m HHJm"#m*m1#!3#,!'m+',-!>"'!m!-,m3,m4*-0mm"#mGYFFm+'#,201m/3#m#*mmHm #1m1'*#,!'-1-Ym m .0-2#>,m ;m #,m ,#)*-#-m #129m '#,m "#1!0'2Ym 12m .0-2#>,m !-,2'#,#m 20#1m "-+','-1m^'%30mJYL_Ym*m"-+','-m+',-m2#0+',*m^+',-9!'"-1mGjIHK_m!-,2'#,#m20#1m 1#%+#,2-1m 20,1+#+ 0,Ym 6.0#1,"-m *m .0-2#>,m ;m #,m *#4"30m 1#m &m "#+-120"-m /3#m #12#m .0'+#0m "-+','-m #1m #*m 0#1.-,1 *#m "#m *m 3,'A,m !-,m #*m #2'*#,-m ^!&**#0m7m*##!)#0ZmGOOK_Ym"#+91Zm*m+32!'A,m#20GjGm*-!*'8"m#,m#12#m"-+','-m .'#0"#m*m!.!'""m"#m3,'A,m!-,m*m&-0+-,m^!&**#0m7m*##!)#0ZmGOOK_Ym *m 1#%3,"-m "-+','-m ^+',-9!'"-1m IHLjLFO_m 1#m #,!3#,20m #,m 3,m 0#%'A,m /3#m .0#1#,2m &-+-*-%>m !-,m "-+','-1m 2'.-m &'12'"',m /3',1m 7m "#m *m !3* 1#m &m "#+-120"-m 13m !2'4'""m /3',1m #(O 0#.,)m ^+ *#m 7m !-*YZm GOONZm HFFH_Ym *m B*2'+-m "-+','-m ^+',-9!'"-1m LGFjMIN_m #1m #*m 0#1.-,1 *#m "#m 0#!' '0m #*m $-1$2-m .0-4#,'#,2#m "#m *m !2'4'""m "#m *m &'12'"',m "#*m "-+','-m ,2#0'-0m ^&,%m 7m !-*YZm GOOI_m 7m .-0m *-m 2,2-m 0#1.-,1 *#m "#m *m 0#%3*!'A,m "#m *m 0#1.3#12m &!'m #*m ',2#0'-0m !#*3*0m "#m *m .0-2#>,m;Ymm m (&30 TEMG[m1203!230m"#m*-1m"-+','-1m'"#,2'$'!"-1m#,m#*m%#,m;m"#m,#)*-#-Em"m"-+','-m2'#,#m 3,m$3,!'A,m"'12',2m7m#,m$3!1'm1#m"#2**m*m.-1'!'A,m"#m*m&'12'"',mIILm"#m*m1#!3#,!'m+',-!>"'!Zm 0#1.-,1 *#m"#m*m$-1$-0'*!'A,m"#*m"-+','-m0#%3*"-0Ym m GMNm m )OO #-/-#9(m ,m,#)*-#-m1#m&,m'"#,2'$'!"-m+32!'-,#1m#,m#*m.0'+#0m"-+','-m/3#m.0-"3!#,m ',1#,1' '*'""m *m #2'*#,-m #,m *1m .-1'!'-,#1m *IG*Zm *#LH&#Zm 71LK70m 7m *GFH&0m^'%30mJYMm#,m+0'**-_m^'*)',1-,m7m!-*YZmGOOK_Ym ,m2-+2#m1#m&,m.-"'"-m'1*0m*-1m%#,#1m;FO<FO=OIJFO>m 7m?Ym*m#123"'-m"#m#12-1m%#,#1m&m1'"-m+37mB2'*m.0m.-"#0m!-+.0#,"#0m+#(-0m *m !2'4'""m "#*m %#,m ;m 7m 13m $+'*'m %<,'!Ym *m !-+.00m *m 1#!3#,!'m "#m #12-1m !320-m%#,#1m1#m&m"#+-120"-m/3#m*m0#%'A,m+91m!-,1#04"m#1m*m0#1.-,1 *#m"#m *m3,'A,m!-,m#*m#2'*#,-m^'#+,m7m!-*YZmHFFF_Ym"#+91Zm#*m%#,m?m&m.#0"'"-m*m &'12'"',mIILm"#*m"-+','-m&'12'"',m/3',1m^'%30mJYL_m.0#,2#+#,2#m0#1.-,1 *#m "#m*m$-1$-0'*!'A,m"#*m2#0!#0m"-+','-Zm"#+-120,"-m/3#m*m!2'4'""m"#m*m&'12'"',m ,-m.0#!#m',"'1.#,1 *#m.0m*m0#1.3#12m*m#2'*#,-m^'#+,m7m!-*YZmHFFF_Ymm 6'12#,m -201m +32!'-,#1m 0#*#4,2#1m /3#m &,m 73""-m #,m *m !-+.0#,1'A,m "#m *m $3,!'-,*'""m"#*m%#,m;Ym-0m#(#+.*-Zm#,m2-+2#m1#m'"#,2'$'!Am#*m+32,2#m0,O ,#*m^Zm_Ym12#m+32,2#m.0-"3!#m$032-1m/3#m,-m+"30,m^'!)m7m3*2#0ZmGOKL_Zm 7m /3#m #1m ',1#,1' *#m *m #2'*#,-m #,m 2-"-1m *-1m 2#('"-1m ^,&,m 7m !-*YZm GOOJ_Ym m +32!'A,m 0#1.-,1 *#m "#m #12#m $#,-2'.-m #1m 3,m !+ '-m "#m .0-*',m m *#3!',m #,m *m .-1'!'A,mILm^'*)',1-,m7m!-*YZmGOOK_m^'%30mJYM_Ymm ,m 4#8m '"#,2'$'!"1m *1m +32!'-,#1m "#1!0'21m #,m ,#)*-#-m 7m #,m 2-+2#m /3#m $#!2,mm*m$3,!'-,*'""m"#*m%#,m.0-"3!'#,"-m',1#,1' '*'""mm#2'*#,-Zm.0-!#"'+-1m m !-+.00*1m !-,m *-1m .-*'+-0$'1+-1m /3#m 1#m & >,m '"#,2'$'!"-m +#"',2#m !-m #,m +#*A,Ym -,m 3,m *',#+'#,2-m +B*2'.*#m ^'%30m JYM_m "#m *-1m %#,#1m ;m "#m ,#)*-#-m ^.;_Zm #*m ;O "#m 2-+2#m ^;_Zm Jm 7m Km "#m 2-+2#m ^>FO ?_Zm #*m m "#m 2-+2#m ^_m 7m #*m ;m "#m +#*A,m ^';_m &#+-1m .-"'"-m '"#,2'$'!0m 7m !-+.00m *1m .-1'!'-,#1m "#m *-1m .-*'+-0$'1+-1m 7m "'1!32'0m 13m #$#!2-Ymm ,m 4#0"#m #,m *m '%30m JYMm 1#m "#2**m #*m .-*'+-0$'1+-m #,!-,20"-m +#"',2#m !-m #,m +#*A,Ym 12#m m .0-4-!m 3,m 1312'23!'A,m "#m #3HHJ*m ^'%30m JYM_Ym 12#m !+ '-m 1#m *-!*'8m #,m *m 0#%'A,m "#*m "-+','-m 20,1+#+ 0,m ^1#,1-0j 0#!#.2-0m "#*m #2'*#,-_m 7m .-0m *-m 2,2-m !-',!'"#m #,m *m 0#%'A,m #,m /3#m 1#m &,m "#1!0'2-m +32!'-,#1m/3#m$#!2,mm*m$3,!'-,*'""m"#m*m.0-2#>,m#,m,#)*-#-m7m#,m2-+2#m ^'*)',1-,m7m!-*YZmGOOK_Ym12m1312'23!'A,m^#3HHJ*_m1#09m.0- *#+#,2#m2-*#0"m 7m/3#m1'm,-1m$'(+-1m#,m*m1#!3#,!'Zm2,2-m#,m2-+2#m!-+-m#,m,#)*-#-m#6'12#,m 0#!#.2-0#1m/3#m!-,2'#,#,m3,m4*',m#,m#12m.-1'!'A,Zm*-m/3#m$4-0#!#m.#,10m/3#m#*m +32,2#m"#m+#*A,m,-m.0-4-!0>m,',%B,m!+ '-m#,m*m$3,!'-,*'""m"#m*m.0-2#>,m ^'%30mJYM_Zm"2-m!-00- -0"-m+#"',2#mYm GMOm #-/-#9( ) m AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 ---------------------------MEVCNC-IEPQWPADELLMKYQYISDFFIAIAY ---------------------------MENCYC-IEPQWPADELLMKYQYISDFFIALAY -------------MGSLLRMNRLLSSIVESCNCIIDPQLPADDLLMKYQYISDFFIALAY ---------------------------MESCDC-IEALLPTGDLLVKYQYLSDFFIAVAY MLAMLRLLFLVLLISLVIISVSANDGEFFNC-CDEDGFWSIHT-ILDCQKVSDFFIAVAY ---MLRTLASALLVLSFFVSLSAADNGFPRCNCDDEGFWSIES-ILECQKISDLFIAIAY . * * : . ::. * :**:***:** 32 53 47 32 58 56 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 FSIPLELIYFVKKSAVFPYRWVLVQFGAFIVLCGATHLINLWTFT-THSRTVALVMTTAK FSIPLELIYFVKKSAVFPYRWVLVQFGAFIVLCGATHLINLWTFT-MHSRTVAVVMTTAK FSIPVELIYFVKKSAVFPYRWVLVQFGAFIVLCGATHLINLWTFN-MHTRNVAIVMTTAK FSIPLELIYFVHKSACFPYRWVLMQFGAFIVLCGATHFISLWTFF-MHSKTVAVVMTISK FSIPLELLYFISRSN-LPFKWVLVQFIAFIVLCGLTHLLNGWTYNPHPSFQLILSLTVAK FSIPIELLYFVSCSN-FPFKWVLFQFIAFIVLCGMTHLLNFWTYYGQHPFQLMLALTIFK ****:**:**: * :*::***.** ******* **::. **: . : : :* * 91 112 106 91 117 115 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 VLTAVVSCATALMLVHIIPDLLSVKTRELFLKNKAAELDREMGLIRTQEETGRHVRMLTH VLTAVVSCATALMLVHIIPDLLSVKTRELFLKNKAAELDREMGLIRTQEETGRHVRMLTH ALTALVSCITALMLVHIIPDLLSVKTRELFLKKKAAQLDREMGIIRTQEETGRHVRMLTH MLTAAVSCITALMLVHIIPDLLSVKTRELFLKTRAEELDKEMGLIIRQEETGRHVRMLTH ILTALVSCATAITLLTLIPLLLKIKVRELFLAQNVLELDQEVGMMKKQTEASMHVRMLTH VLTALVSFATAITLITLFPMLLKVKVREFMLKKKTWDLGREVGLIKMQKEAGWHVRMLTQ *** ** **: *: ::* **.:*.**::* .. :*.:*:*:: * *:. ******: 151 172 166 151 177 175 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 EIRSTLDRHTILKTTLVELGRTLALEECALWMPTRTGLELQLSYTLRHQ---HPVEYTVP EIRSTLDRHTILKTTLVELGRTLALEECALWMPTRTGLELQLSYTLHQQ---NPVGYTVP EIRSTLDRHTILKTTLVELGRTLALEECALWMPTRTGLELQLSYTLRHQ---NPVGLTVP EIRSTLDRHTILKTTLVELGRTLDLAECALWMPCQGGLTLQLSHNLNNL---IPLGSTVP EIRKSLDKHTILYTTLVELSKTLKLQNCAVWMPNESRSQMNLTHELSPSSAAESHRS-LS EIRKSLDRHTILYTTLVELSKTLDLHNCAVWKPNENKTEMNLIHELRDSSFNSAYNLPIP ***.:**:**** ******.:** * :**:* * . ::* : * . :. 208 229 223 208 236 235 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 IQLPVINQVFGTSRAVKISPNSPVARLRPVSGKYMLGEVVAVRVPLLHLSNFQINDWPEL INLPVISQVFSSNRALKISPNSPVASLRPRAGRYVAGEVVAVRVPLLHLSNFQINDWPEL IQLPVINQVFGTNHVVKISPNSPVARLRP-AGKYMPGEVVAVRVPLLHLSNFQINDWPEL INLPIINEIFSSPEAIQIPHTNPLARMRNTVGRYIPPEVVAVRVPLLHLSNFTN-DWAEL INDPDVLEIT-KNKGVRILRQDSVLAASSSGGSGEPCAVAAIRMPLLRASDFKG-GTPEL RSDPDVIQVK-ESDGVKILDADSPLAVASSGGSREPGAVAAIRMPMLKVSNFKG-GTPEL . * : :: ::* .. * *.*:*:*:*: *:* . .** 268 289 282 267 294 293 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 STKRYALMVLMLPSDSARQWHVHELELVEVVADQVAVALSHAAILEESMRARDLLMEQNV STKRYALMVLMLPSDSARQWRVHELELVEVVADQVAVALSHAAILEESMRARDLLMEQNV STKRYALMVLMLPSDSARQWHVHELELVEVVADQVAVALSHAAILEESMRARDLLMEQNV STRSYAVMVLVLPMNGLRKWREHELELVQVVADQVAVALSHAAILEDSMRAHDQLMEQNI VDTRYAILVLVLSSVDERVWSYDEMEIVEVVADQVAVALSHATVLEESQTMREKLEMRNR VPECYAILVLVLPSEQGRSWCSQEIEIVRVVADQVAVALSHAAILEESQHMRETLEEQNR **::**:*. * * .*:*:*.*************::**:* :: * :* 328 349 342 327 354 353 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 ALDLARREAETAIRARNDFLAVMNHEMRTPMHAIIALSSLLQETELTPEQRLMVETILKS ALDLARREAETAIRARNDFLAVMNHEMRTPMHAIIALSSLLQETELTPEQRLMVETILKS ALDLARREAEMAVRARNDFLAVMNHEMRTPMHAIIALSSLLQETDLTPEQRLMVETILKS ALDVARQEAEMAIRARNDFLAVMNHEMRTPMHAVIALCSLLLETDLTPEQRVMIETILKS VLQQAQENAMKASQARTSFQKVMNNGMRRPMHSILGLLSIFQDEKASSDQRMIVDTMVKT ALEQAKQDALRASQARNAFQMVMSHGLRRPMHSILGLLSLLQDEKLGNEQRLLVDSMVKT .*: *:.:* * :**. * **.: :* ***:::.* *:: : . :**:::::::*: 388 409 402 387 414 413 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 SNLLATLMNDVLDLSRLEDGSLQLELGTFNLHTLFREVLNLIKPIAVVKKLPITLNLAPD SNLLATLINDVLDLSRLEDGSLQLDIGTFNLHAVFKEVLNLIKPVTLVKKLSLTLHLGPD SNLLATLINDVLDLSRLEDGSLQLDIGTFNLHALFREVHSLIKPIASVKKLFVTLSLSSD SNLLATLINDVLDLSRLEDGILELENGTFNLHGILREAVNLIKPIASLKKLSITLALALD STVLSTLINDAMEISAKDDGRFPVEMKPFQLHLLVREASCLVKCLCVYKGFGFSTDVPTS SNVVSTLIDDVMDTSTKDNGRFPLEMRYFQLHSMIKEAACLAKCLCAYRGYNISIEVDKS *.:::**::*.:: * ::* : :: *:** :.:*. * * : : .: : . 448 469 462 447 474 473 AtETR1 CmETR1 LeETR1 LPEFVVGDEKRLMQIILNIVGNAVKFSKQGSISVTALVTKSDT----RAADFFVVPTGSH 504 LPVFAVGDEKRLMQAILNVVGNAVKFSKEGSISISAIVAKSETFREIRVPDFHPVPSDSH 529 LPEYVIGDEKRLMQILLNVVGNAVKFSKEGNVSISAFVAKSDSLRDPRAPEFFAVPSENH 522 GNFm )OO #-/-#9(m LeNR LeETR5 LeETR4 LPILAVGDAKRLIQTLLNVAGNAVKFTKEGHISIEASVAKPEYARDCHPPEMFPMPSDGQ 507 LPNQVMGDEKRTFQVLLHMVGHLLNVSIGKGSVIFRVVLETGAETGNDKVWGTRRPSTTD 534 LPNHVLGDERRVFQVILHMVGNLLKDPNG-GLLTFRVLPESVSREGIGGAWRTRRSNSSR 532 ** .:** :* :* :*::.*: :: . : :. .. AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 FYLRVKVKDSGAGINPQDIPKIFTKFAQTQSLATRSSGGSGLGLAISKRFVNLMEGNIWI FYLRVQVKDTGSGISPQDIPKLFTKFAQTT-VGPRNSGGSGLGLAICKRFVNLMEGHIWL FYLRVQIKDTGIGITPQDIPNLFSKFTQSQALATTNSGGTGLGLAICKRFVNLMEGHIWI FYLRVQVRDTGCGISPQDIPLVFTKFAESRPTSNRSTGGEGLGLAICRRFIQLMKGNIWI EYVTIKFEIEVSLEGSQSDSSISTIHFGGRRHNSKEVT-EGLSFNMCKKLVQMMQGNIWM DNAYIRFEVGTSNNHSQPEGTMLPHYRPKR--CSKEMD-EGLSFTVCRKLVQLMQGDIWV ::.. .* : . . . **.: :.::::::*:*.**: 564 588 582 567 593 589 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 ESDGLGKGCTAIFDVKLGISERSNES-KQSGIPKVPAIPRHSNFTGLKVLVMDENGVSRM ESEGLGKGCTATFIVKLGIADQSNES-KLPYTSKIHENSIHTSFPGLKVLVMDDNG---ESEGLGKGSTAIFIIKLGIPGRANES-KLPFVTKLPANHTQMSFQGLKVLVMDENGVSRM ESEGPGKGTTVTFVVKLGICHHPNALPLLPMPPRGRLNKGSDDLFRYRQFRGDDGGMS-SSNAQGHAQGMTLILRFQKQSSFRKR-MFEYRNPLEQPISSTMFRGLHVLLTDDDDVNRL IPNPEGFDQSMAVVLGLQLRPSIAIG-IPEYGESSDHSHPHSLLQGVKVLLADYDDVNRA .: * . : : : : : * .. 623 643 641 625 652 648 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 VTKGLLVHLGCEVTTVSSNEECLRVVSHEHKVVFMDVCMPGVENYQIALRIHEKFTKQRH -----------------------------------------------------------VTKGLLTHLGCDVTTVGSRDECLRVVTHEHKVVIMDVSMQGIDCYEVAVVIHERFG-KRH ------------------------------------------------------VNAQRY VTRKLLEKLGCQVTAVSTGFQCLSALGPSLTTFQVLILDLQMPEMDGYEVALRVRKFRSR VTSKLLEKLGCSVSAVSSGRDCIGVLSPAVSSFQIVLLDLHLPDLDGFEVTMRIRKFGSH 683 AtETR1 CmETR1 LeETR1 LeNR LeETR5 LeETR4 QRPLLVALSGNTDKSTKEKCMSFGLDGVLLKPVSLDNIRDVLSDLLEPRVLYEGM ------------------------------------------------------GRPLIVALTGNTDRVTKENCMRVGMDGVILKPVSVYKMRSVLSELLEHGVVLESQRSL--------------------------------------------------SWPLIIALTASSEEQVWEKCLQVGMNGLIRKPVLLQGLADELQRLLQRGGGGDGL NWPLIVGLTATADENVTGRCLQIGMNGLIRKPVLLPGIADELQRVLLRGSRMM-- 700 631 712 708 738 754 635 767 761 m (&30 TEMH[m*',#+'#,2-m+B*2'.*#m"#m*-1m%#,#1m;m#,m,#)*-#-Zm2-+2#m7m+#*A,m7m*-1m%#,#1m>Fm ?m7mm"#m2-+2#Ym,m!-*-0m+0'**-m*1m+32!'-,#1m#,m,#)*-#-m/3#m.0-4-!,m',1#,1' '*'""m#,m #2'*#,-Zm#,m0-(-m*m+32!'A,m"#*m$#,-2'.-m,m^0,O#*_Zm#,m$3!1'm*m&'12'"',m!-,m!2'4'""m$-1$-0'*,2#m #,m#*m%#,m;m"#m,#)*-#-O7m#,m4#0"#m#*m!+ '-m"#2#!2"-m+#"',2#m!-m#,m+#*A,Ym m *mm"'1.-,#m"#m',$-0+!'A,m$#,-2>.'!m"#m!0!2#0#1m+-0$-*A%'!-1m!-+-m#*m !-*-0m"#m*m.3*.Zm#*m0-+m7m#*m1 -0m.0m*%3,1m"#m*1m40'#""#1Ym,m*m *m JYKm 1#m "#2**,m *%3,-1m "#m *-1m !0!2#0#1m /3#m .0#!#,m #120m 0#*!'-,"-1m !-,m *m !2'4'""m "#*m #2'*#,-m "30,2#m #*m .0-!#1-m "#m *m +"30!'A,m "#*m $032-Zm !-+-m *m !-,1'12#,!'m"#m*m.3*.Zm*m',2#,1'""m"#*m0-+m-m*m+"30!'A,m!*'+2<0'!Ym1mJm !!#1'-,#1m"#1!0'21m#,m*m *mJYKm.0#1#,2,m#*mmGm/3#m!31m*m1312'23!'A,m"#m #3HHJ*m 7m 1#m !0!2#0'8,m .-0m 2#,#0m *m !0,#m *,!m ^'%30m JYN_m 7m "#+91Zm 3,m 0-+m 7m "3*830m +#,-1m ',2#,1-1m /3#m #,m -201m 40'#""#1Ym ,m "#m #**1m .0#1#,2m +"30!'A,m2'.-m!*'+2<0'!-Zm"-1m"#m#**1m,-Zm7m.0m"-1m+91m,-m#61'2#,m"2-1m1- 0#m 2'.-m"#m+"30!'A,Ym m GNGm #-/-#9( ) !+ TEMFOT0!2#0>12'!1m$#,-2>.'!1m"#m*1m!!#1'-,#1m/3#m.0#1#,2,m#*mmGm^"#m*m40'#""mmHNHJJNZm /3#m2+ '<,m.0#1#,2m#*mmGZm,-m1#m"'1.-,#m"#m"2-1_Ym[m-m&7m"2-1m"'1.-,' *#1Ym m .+.0T7T ".-1(12$-"( T #$T+ TT /3+/ T *,!i+#"'-j *,"m -2$-1(# #T #$+T 0., T 3+830 T #30 "(>-T "+(, 2:0(" T !'"m ,-m"3*!#m 'mm m m m m &)-,"m ^'+ 5#_m *,!i"30m ,-m0-+m ,-m"3*!#m -m '%3',!&-0m ^#,#%*_m *,!i+#"'-j *,"m .-!-m 0-+92'!-m .-!-m"3*!#m -m .,!0$T 4 0($# #T 1//T 0(&$-T IJOm +#*-m 0)m mGHJGGHm %0#12'1m ,"'m mJNHJHOm %0#12'1m mJILKIJm %0#12'1m m (&30 TEMIOT+%#,m "#m *1m !!#1'-,#1m #,m *1m /3#m 1#m &,m "#2#!2"-m #*m m Gm /3#m .0-4-!m 3,m !+ '-m "#m +',-9!'"-m#,m#*m.0'+#0m+.*'!A,m"#*m%#,m;m^"#mmHNHJJNm,-m1#m"'1.-,#m"#m'+%#,_Ym T -0m 2,2-Zm *m ',$-0+!'A,m "#m /3#m 1#m "'1.-,#m ,-m .#0+'2#m $'0+0m /3#m *m +32!'A,m "#2#!2"m#,m#*m%#,m;m#12<m'+.*'!"m#,m!+ '-1m#,m#*m2'.-m"#m+"30!'A,m"#*m $032-Ymmm GNHm -./#)O ().7*#)O #-/-#9(m m EMETTTTTTTT m ,'!'*+#,2#m#*m- (#2'4-m"#*m#123"'-m$#,-2>.'!-m"#mJFFm$+'*'1mHm"#m*m.- *!'A,m"#m m !0#"m #,m #12#m 20 (-m #0m #,!-,200m +32,2#1m !-,m !0!2#0>12'!1m "#m ',2#0<1m !-+#0!'*Ym - 0#2-"-Zm #,m !0!2#0#1m "#*m $032-m !A+-m *m $-0+Zm #*m !-*-0Zm #*m #1!0'230"-m7m2+ '<,m#,m!0!2#0#1m"#m*m.*,2m!-+-m*%B,m2'.-m"#m0#1'12#,!'Zm.-0m #(#+.*-Zm 0#1'12#,!'m *m ->"'-m ^))-*",O 2(."##_Ym #m !0#!'#0-,m "'#8m .*,21m .-0m $+'*'m.0m.-"#0m- 1#040m1'm& >m+91m"#m3,m.*,2m.-0m$+'*'m/3#m+-120 m#*m $#,-2'.-m +32,2#m 7m "#m #12#m +-"-m !-,$'0+0m /3#m #0m 3,m $#,-2'.-m .0-"3!2-m "#m 3,m +32!'A,m&#0#""m7m,-m3,m#$#!2-m+ '#,2*Ym 201m .*2$-0+1m "#m m &,m "#100-**"-m 1#1m "#m "2-1m "-,"#m 1#m -$0#!#m "#+91m3,m1#04'!'-m/3#m.0-.-0!'-,m*1m1#+'**1m"#*m+32,2#m/3#m1#m"#1##m#123"'0Ym 1m 1#1m"#m"2-1m$!'*'2,m+<2-"-1m"#m B1/3#"m 1"-1m#,m#*m%#,m"#m',2#0<1m.0m #*m !3*m /3#0#+-1m #,!-,200m +32,2#1m -m 1"1m #,m *m B1/3#"m "#m 3,m $#,-2'.-m !-,!0#2-Ym-0m#(#+.*-Zm#,m#*m!1-m"#m*m 1#m"#m"2-1m"#mm^OO .-_m^&22.[ii30%4Y#407Y',0Y$0i!%'j ',i.0-(#!21i'**',%i',"#6Y.*_m1#m.3#"#m!!#"#0m m*m',$-0+!'A,m0#!-.'*"m"#m20#1m.- *!'-,#1m"'12',21m"#m[m3)*,-#/'O -/&(./'FO #-/'O -.#0/'O 7O ,"3*)#/'O #-."3)(O ^'%30m JYOZm G_YO 0m !"m 3,m "#m #**1Zm 1#m .3#"#m 0#*'80m 3,m B1/3#"m #,m $3,!'A,m "#*m %#,m #,m #*m /3<m .-"+-1m #120m ',2#0#1"-1m O ^'%30m JYOZm H_m -m '#,m 3,m $#,-2'.-m 7m !0!2#0'8"-O ^'%30m JYOZm H _Ym ,m #12m 1#m "#m "2-1m 2'#,#,m !0!2#0'8"-1m IGm %#,#1m !-,m KKOm +32!'-,#1m 7m HYJFKm $#,-2'.-1Zm13+,"-m*-1m0#13*2"-1m- 2#,'"-1m.0m*1m20#1m#1.#!'#1Ym'm1#m1#*#!!'-,m *%B,m %#,Zm *m 1#m "#m "2-1m .0-.-0!'-,m ',$-0+!'A,m 1- 0#m *1m $+'*'1m +32,2#1m /3#m1#m&,m"#2#!2"-m.0m<12#m^'%30mJYOZmIZm!-+-m#(#+.*-m1#m&m1#*#!!'-,"-m#*m %#,m I#-)J>_Ym -12#0'-0+#,2#Zm 2+ '<,m 1#m .3#"#m - 2#,#0m ',$-0+!'A,m +91m "#2**"m ^'%30m JYOZm J_m #"-,"#m 1#m +3#120m *m 1#!3#,!'m "#*m %#,m 7m *m .-1'!'A,m !-,!0#2m "#m *m +32!'A,m 2,2-m m ,'4#*m ,3!*#-2>"'!-m !-+-m +',-!>"'!-YO -0m -20-m *"-Zm 1#m .3#"#m 1#*#!!'-,0m 3,m $#,-2'.-m ^'%30m JYOZm I _m 7m m .02'0m "#m <12#m 4#0m '+9%#,#1m7Zm#,m*%3,-1m!1-1Zm1'm1#m&m"#2#!2"-m*%3,m+32!'A,m#,m*m$+'*'m"#m*m '+%#,m1#*#!!'-,"m^'%30mJYOZmJ _Ym ,m "#$','2'4Zm #12m 1#m "#m "2-1m #1m 3,m #(#+.*-m "#m !-+-m 1#m .3#"#m #6.*-20m *m ',$-0+!'A,m- 2#,'"m#,m3,m-m40'1m.*2$-0+1m"#mYm#m#12#m+-"-Zm*1m GNIm #-/-#9( -./#)O ().7*#) +32!'-,#1m #129,m '#,m '"#,2'$'!"1m 7m 1-,m "#m 31-m .B *'!-m "#m +-"-m /3#m 2-"m *m !-+3,'""m!'#,2>$'!m.3#"#m!!#"#0mm#**1Ymm mm (&30 TEMJTOm,$-0+!'A,m"'1.-,' *#m#,m*m 1#m"#m"2-1m" Ym#m.3#"#m0#*'80m*m B1/3#"m.0m3,m %#,m!-,!0#2-m^4>mZm#,m4#0"#_m-m#,m$3,!'A,m"#m3,m$#,-2'.-m^4>mFm#,m83*_Ym m ,m ,3#120-m !1-m ,-m 1#m &m 0#*'8"-m 3,m 1#m "#m "2-1m .#0-m #,m 3,m $3230-m "# #0>m "'1#@01#m /3'891m !-,(3,2+#,2#Zm !-,m *1m -201m .*2$-0+1m "# m "#100-**"1m#,m#12m+'1+m#1.#!'#Ym-0m#*m+-+#,2-Zm#,m#12#m20 (-m1'm1#m&m&#!&-m 3,m .0'+#0m !29*-%-m $#,-2>.'!-m 7m /3#m "30,2#m #*m @-m HFFMZm 1#m 1'%3'Am !-,m "#2**#m #*m !0#!'+'#,2-m "#m JFFm $+'*'1m Hm "#1"#m *m %#0+',!'A,m &12m *m - 2#,!'A,m "#m $032-Ym ,m #12#m .#0>-"-m 1#m 2-+0-,m '+9%#,#1m .0m .-"#0m 0#%'1200m /3#**-1m +32,2#1m !-,m ,3#4-1m$#,-2'.-1Ym*m- (#2'4-m#0m4'13*'80m$#,-2'.-1m7m"#2#0+',0m#*m,B+#0-m7m*m "'4#01'""m "#m *-1m +'1+-1Zm 2+ '<,m !-+-m "2-m !-,$'0+2'4-m "#m /3#m *m .- *!'A,m #12 m +32"m !-,m 3,m !'#02m #$'!'#,!'Ym 1#04+-1m $#,-2'.-1m m ,'4#*m "#m .'%+#,2!'A,m !-,m .*,21m !*-0A2'!1m -m .0!'*+#,2#m !*-0A2'!1Ym + '<,m m ,'4#*m "#m !0#!'+'#,2-m "#m *m .*,2m - 1#04,"-m $#,-2'.-1m #,,-1Ym m ,'4#*m "#m "#100-**-m - 1#04+-1 #,m *%3,1m $+'*'1m !0#!'+'#,2-m 1',m "-+',,!'m .'!*m 7m !-,m 3,m "#100-**-m ',2#0,-"*m +3!&-m +7-0Ym ',*+#,2#m 1#m - 1#040-,m $+'*'1m +32,2#1m GNJm -./#)O ().7*#)O #-/-#9(m #,m*m$-0+m7m!0!2#0>12'!1m"#*m$032-Ym-1m$#,-2'.-1m"#1!0'2-1m#,m#*m!29*-%-m.3#"#,m 1#0m3,m','!'-m.0m*m!0#!'A,m"#m3,m 1#m"#m"2-1m+91m!-+.*#2Ymm -0m #(#+.*-Zm *-1m $#,-2'.-1m "#1!0'2-1m !-,m .<0"'"m "#m *m "-+',,!'m .'!*m .-"0>,m .-1##0m3,m"#$'!'#,!'m#,m*m '-1>,2#1'1m-m 20,1.-02#m "#m *1m 36',1m -m !'2-/3',',1Zm 7m /3#m #121m &-0+-,1m 1-,m *1m /3#m 0#%3*,m #*m !0#!'+'#,2-m !-,m "-+',,!'m .'!*m ^-&,j-301#3Zm HFGF_Ym 0m -20-1m $#,-2'.-1m #1m +91m !-+.*'!"-m "#2#0+',0m /3#m %#,#1m .3#"#,m 1#0m 0#1.-,1 *#1m "#m *-1m !0!2#0#1m +32,2#1Ym ',m #+ 0%-Zm *%3,-1m $#,-2'.-1m.3#"#,m1#0m',2#0#1,2#1mm,'4#*m%0-,A+'!-m7m!-+#0!'*m1',m,#!#1'""m"#m 1 #0m !39*#1m 1-,m *-1m %#,#1m 0#1.-,1 *#1m "#m #1#m #$#!2-Ym -0m #(#+.*-Zm 1#m &,m #,!-,20"-m$+'*'1m!-,m!0!2#0>12'!1m"'$#0#,2#1m!-+-m*m$-0+m7m#*m!-*-0m"#m$032-m 0#1.#!2-m *m 40'#""m LHjGGIYm ,m *%3,m $+'*'m *-1m $032-1m 1-,m +3!&-m +91m 0#"-,"#"-1m^'%30mJYGF_m7m""-m/3#m#*m+#*A,m2>.'!-m"#mc'#*m"#m1.-cm#1m#*>.2'!-m #12#m ,3#4-m !09!2#0m .-"0>m 1#0m ',2#0#1,2#m m ,'4#*m !-+#0!'*Ym #1.#!2-m *m !-*-0Zm 1#m &,m #,!-,20"-m $+'*'1m !-,m 3,m !-*-0m *'1-Zm 1',m #1!0'230"-m ^'%30m JYGF_m 7m 2+ '<,m #,m#12#m!1-m.-"0>m1#0m3,m!09!2#0m',2#0#1,2#mm,'4#*m!-+#0!'*m.3#12-m/3#m.-"0>m 0#13*20m 20!2'4-m .0m #*m !-,13+'"-0Ym m #*#!!'A,m "#m #12-1m $#,-2'.-1m .0m 13m ',!*31'A,m#,m.0-%0+1m"#m+#(-0m%#,<2'!m"# #m1#0m4*-0"m.-0m*1m#+.0#11m"#m 1#+'**1m1'#+.0#m/3#m1#m!-,$'0+#,m*-1m$#,-2'.-1m#,m%#,#0!'-,#1m+91m4,8"1Ym m m m (&30 TEMBA[m8/3'#0"[m+%#,m"#*m$032-m"#m*m$+'*'mGOFHm!-,m*m.'#*m*'1Zm1',m+,!&1m,'m#1!0'230"-Ym #0#!&[m +%#,m "#*m $032-m "#m *m $+'*'m HHNLm !-,m 3,m $-0+m 0#"-,"#"m 2-2*+#,2#m "'12',2m m *m #*>.2'!Zm2>.'!m"#*m+#*A,mb'#*m"#m1.-cYm m ,m 4#8m !0!2#0'8"-1m *-1m $#,-2'.-1m #,!-,20"-1m #,m *m .- *!'A,m "#m m "#m +#*A,m .-"#+-1m !-+.00*-1m !-,m *-1m $#,-2'.-1m "#2#!2"-1m #,m *1m .- *!'-,#1m GNKm #-/-#9( -./#)O ().7*#) "#100-**"1m #,m -201m #1.#!'#1Ym ,m *m '%30m JYGGm 1#m +3#120,m $#,-2'.-1m #,!-,20"-1m #,m -201m .- *!'-,#1m "#m m "#m -201m #1.#!'#1[m )&(/'O &3)*,-#/'m^',-'m7m!-*YZmHFGF_Zm#-/'O-.#0/'m^*+'1m7m!-*YZmHFFN_m-m#,m+#*A,m #,m *m 40'#""m 2'.-m &0#,2'1Zm &0-,-m ^&+,'j0"1m 7m !-*YZm HFGF_m 7m /3#m +3#120,m !'#02m 1#+#(,8m !-,m $#,-2'.-1m #,!-,20"-1m #,m *m .- *!'A,m +32,2#m "#100-**"m#,m#12#m20 (-Ymm"#$-0+!'A,m"#m!-2'*#"-,#1m^'%30mJYGGZm_Zm*m$*2m "#m .'%+#,2!'A,m -m .0#1#,!'m "#m !*-0-1'1m #,m &-(1m ^'%30m JYGGZm _Zm 1>m !-+-m *m +*$-0+!'A,m #,m #*m "#100-**-m .'!*m "#m *m .*,2m ^'%30m JYGGZm _Zm 1-,m *%3,-1m "#m *-1m$#,-2'.-1m/3#m+91m$0#!3#,2#+#,2#m1#m0#.'2#,m#,m*1m.- *!'-,#1m"#mYmm m "#$-0+!'A,m #,m !-2'*#"-,#1m /3#m - 1#04+-1m #,m *m $+'*'m GNMLm #1m .09!2'!+#,2#m'%3*m*m$#,-2'.-m/3#m+-120 m#*m+32,2#m#,m*m40'#""m&0-,-m /3#m .0#1#,2 m !'#02m "#$-0+!'A,m 7m #,0-1!+'#,2-m #,m *-1m !-2'*#"-,#1Ym *m 2'.-m "#m +32!'A,m !-,m !-*-0!'A,m * ',m "#2#!2"m #,m *m $+'*'m ^INJ_m 2+ '<,m 1#m &m "#2#!2"-m#,m*1m"-1m.- *!'-,#1m!-,m*1m/3#m1#m!-+.0,m*-1m$#,-2'.-1Zm1>m!-+-m*m +*$-0+!'A,m%#,#0*'8"m,-m1A*-m#,m*m+-0$-*-%>m"#m*1m&-(1m1',-m2+ '<,m#,m#*m !0#!'+'#,2-m.'!*m"#m*m$+'*'mGKFKm^'%30mJYGG_Ymm GNLm -./#)O ().7*#)O T #-/-#9(m m (&30 TEMBBOm(#+.*-1m"#m$#,-2'.-1m#,!-,20"-1m#,m-201m.- *!'-,#1m"#mYm_m*$-0+!'A,m"#m !-2'*#"-,#1m^GNML_m_m* ','1+-Zm$*2m"#m.'%+#,2!'A,m^INJ_m_m*$-0+!'A,m#,m#*m"#100-**-m.'!*m ^GKFK_Ym1m'+9%#,#1m1#m&,m- 2#,'"-m"#m*1m.- *!'-,#1m"#m)&(/'O&3)*,-#/'m^',-'m7m!-*YZmHFGF_Zm #-/'O-.#0/'m^*+'1m7m!-*YZmHFFN_m7m+#*A,m40'#""m2'.-m&0#,2'1m&0-,-m^&+,'j0"1m7m !-*YZmHFGF_Ym',*+#,2#m1#m&,m@"'"-m*%3,1m'+9%#,#1m"#m+32,2#1m"#m*m.- *!'A,m"#m+#*A,m^LHj GGI_m- 2#,'"1m#,m#12#m20 (-m.0m.-"#0m#12 *#!#0m*m!-+.0!'A,m^-,8*#8j-m7m!-*YZmHFGF_Ym m + '<,m.-"#+-1m#,!-,200m.0*#*'1+-1m#,20#m*-1m$#,-2'.-1m#,!-,20"-1m#,m$032-m #,m #121m .- *!'-,#1m "#m m "#100-**"1m #,m -201m #1.#!'#1Ym ,m *m .- *!'A,m "#m+#*A,m"#100-**"m.-0m&+,'m7m!-* -0"-0#1m$#,-2'.0-,m$032-1m"#*m+#*A,m &0-,-m !-,m 3,m 2+@-m +#,-0m ^'%30m JYGHZm I_m Zm -m !-,m 3,m ,B+#0-m +7-0m "#m !0.#*-1m ^'%30m JYGHZm H_m 0#1.#!2-m *m !-,20-*m ^'%30m JYGHZm G_Ym + '<,m #,m *m .- *!'A,m "#m m "#m 2-+2#m ^',-'m 7m !-*YZm HFGF_m 1#m $#,-2'.0-,m $032-1m /3#m .0#1#,2 ,m3,m$-0+m+91m*0%"m^'%30mJYGHZmG_m-m3,m.'%+#,2!'A,m*2#0"m ^'%30mJYGHZmH_Ym*%3,-1m"#m#12-1m$#,-2'.-1m+32,2#1m2+ '<,m1#m&,m#,!-,20"-m #,m*m.- *!'A,m"#100-**"m#,m#12#m20 (-m^'%30mJYLZmGjH_Ym GNMm #-/-#9( T -./#)O ().7*#) m (&30 T EMBC[m #,-2'.-1m '"#,2'$'!"-1m #,m $032-m #,m -201m .- *!'-,#1m "#m m #* -0"1m #,m +#*A,m ^&+,'m0"1m7m!-*YZmHFGF_m7m#,m2-+2#m^',-'m7m!-*YZmHFGF_Ym#m+3#120,m"-1m#(#+.*-1m"#m+32,2#1m #,!-,20"-1m#,m*m.- *!'A,m"#mm"#100-**"m#,m#12#m20 (-m^-,89*#8j-m7m!-*YZmHFGG_\m3,-m"#m $032-m +37m *0%"-m ^G_m 7m -20-m /3#m ,-m !-,2'#,#m *m .'%+#,2!'A,m -m +,!&1m !0!2#0>12'!1m "#*m '#*m "#m .-m^H_Ymm m -0m*-m2,2-Zm*m!-+.0!'A,m0#1.#!2-mm*-1m$#,-2'.-1m+32,2#1m#,!-,20"-1m#,m-201m .- *!'-,#1m !-,$'0+m *m #$'!'#,!'m "#*m +<2-"-m #+.*#"-m .0m +32%#,'80m #,m +#*A,m7mm13m4#8Zm!-,$'0+ *m2#,"#,!'mm#,!-,200m*%3,1m+32!'-,#1 #1.#!>$'!1m /3#m7m1#m&,m#,!-,20"-m#,m-201m.- *!'-,#1Zm!-+-m.3#"#,m1#0m*m+*$-0+!'A,m "#m !-2'*#"-,#1Zm *m *2#0!'A,m "#m .'%+#,2!'A,m 2,2-m #,m &-(1m !-+-m #,m $032-m 7m *1m +*$-0+!'-,#1m#,m#*m"#100-**-m.'!*m-m6'*m"#m*m.*,2Ym m m GNNm O )(&/-#)(-m m T T 1- #m &m "#100-**"-m 3,m .- *!'A,m "#m m #,m //'#-O '&)m Ym !-,m 3,m 21m "#m +32!'A,m"#mGiGYKm Ym12m,3#4m&#00+'#,2m&m"#+-120"-m1#0mB2'*m.0m*m"#2#!!'A,m "#m+32,2#1m#,m%#,#1m"#m',2#0<1m%0-,A+'!-Ym 2-m.0#&'"02!'A,m"#m*1m1#+'**1m1>m!-+-m*m32'*'8!'A,m"#m (1m"-1'1m"#m+329%#,-m ^FZKPm *m GZKP_m "30,2#m #*m .0-2-!-*-m "#m +32%#,'8!'A,m &,m "#2#0+',"-Zm .0- *#+#,2#Zm *m (m 21m "#m +32!'A,m #,!-,20"Ym 0m "#100-**0m *m .- *!'A,m "#*m m,-m1#m.0#&'"020-,m*1m1#+'**1m7m1#m310-,m"-1'1m+91m*21m"#*m%#,2#m+329%#,-m Zm- 2#,'#,"-m3,m21m"#m+32!'A,m+91m#*#4"m/3#m#,m*m.- *!'A,mYm 3-,m *m ,3#4m .- *!'A,m "#100-**"m 1#m &,m ,*'8"-m !320-m %#,#1[m m 7m *-1m %#,#1m >FO I#-)J>m 7m ;Ym -1m +'1+-1m %#,#1m &,m 1'"-m ,*'8"-1m #,m *m .- *!'A,m "#m m"#*mm.0m.-"#0m#12 *#!#0m3,m!-+.0!'A,m#,20#m+ 1Ym m 4-,m*m.- *!'A,mm1#m&,m"#2#!2"-m"-1m+32,2#1m#,m#*m%#,m"#m*mZm!320-m#,m#*m #JZm ,',%3,-m #,m 13m '1-$-0+m ^I#-)J>Jm 7m ,',%3,-m #,m #*m %#,m GYm 320-m "#m #12-1m +32,2#1m 1#m #,!3#,20,m #,m 8-,m !-"'$'!,2#m ^JiL_m 7m 20#1m "#m #**-1m .-"0>,m $#!20m m *m $3,!'-,*'""m"#m*m.0-2#>,m1#%B,m*-1m4*-0#1m- 2#,'"-1m#,mYm 5-,m*m.- *!'A,mm1#m&,m"#2#!2"-m!320-m+32,2#1m#,m#*m%#,m"#m*mZm!2-0!#m #,m #*m #Jm 7m 3,-m #,m I#-)J>Ym '#2#m "#m #12-1m +32,2#1m 1#m #,!3#,20,m #,m 8-,m !-"'$'!,2#m^MiGO_m7m20#1m"#m#**-1m.-"0>,m$#!20mm*m$3,!'-,*'""m"#m*m.0-2#>,m1#%B,m *-1m4*-0#1m- 2#,'"-1m#,mYm m 6-m #m &m 0#*'8"-m #*m #123"'-m "#m 1#%0#%!'A,m 7m "#m $#,-2'."-m .0m *-1m +32,2#1m "#2#!2"-1m #,m #*m %#,m "#m *m m #,m *m .- *!'A,m Ym ,m *m $+'*'m INJm ,-m 1#m &,m - 2#,'"-m &-+-!'%-2-1m +32,2#1m #,m Hm 7m 1A*-m 1#m &m .-"'"-m - 2#,#0m 3,m &-+-!'%-2-m +32,2#m #,m *m %#,#0!'A,m IZm /3#m .0#1#,23,m $#,-2'.-m * ',-Ym -0m *-m 2,2-Zm &#+-1m 0#*!'-,"-m #12#m $#,-2'.-m !-,m *m +32!'A,m "#*m %#,m Zm /3#m 0#.0#1#,20>m 3,m ',#$'!'#,!'m#,m*m4>m"#m '-1>,2#1'1m"#m!0-2#,-'"#1Ym GNOm )(&/-#)(-O m 7-0m*-1m+32,2#1m#,m#Jm1#m&,m- 2#,'"-m#123"'-1m"#m1#%0#%!'A,m#,mHm.#0-m,-m1#m &m .-"'"-m &!#0m 3,m #123"'-m $#,-2>.'!-Ym ',m #+ 0%-Zm 1'm 1#m &m &#!&-m 3,m #123"'-m "#m .0#"'!!'A,m "#m #1203!230m IZm 13%'0'#,"-m /3#m *%3,1m +32!'-,#1m .3#"#,m $#!20m *m $3,!'-,*'""m"#m*m.0-2#>,Zm!-+-m.-0m#(#+.*-m*m$+'*'mKMm!-,m#*m!+ '-m*3GHO71Ym 8-30,2#m #12#m 20 (-m 2+ '<,m 1#m 0#*'8Am 3,m #123"'-m "#m !-m !-+.0,"-m GGIm 40'#""#1m"#m+#*A,m!-,m*m40'#""m"#m0#$#0#,!'mLHjGGIYm12#m#,17-m1#m&'8-m!-,m*-1m %#,#1m>m7m;Ym,m+ -1m%#,#1m1#m#,!-,200-,m"'$#0#,2#1m&.*-2'.-1m!-,m1m/3#m .0-4-!,m 3,m !+ '-m "#m +',-9!'"-m 7m .3#"#,m $#!20m *m $3,!'-,*'""m "#m + 1m .0-2#>,1m 1#%B,m *-1m 4*-0#1m - 2#,'"-1m #,m Ym #"',2#m !-m 1#m &,m "#$','"-m ,3#4-1m &.*-2'.-1m -m 40'!'-,#1m ,230*#1m /3#m ,-m & >,m 1'"-m "#1!0'21m !-,m ,2#0'-0'""Ym 9-m #m &m #* -0"-m 3,m !29*-%-m "#m +32,2#1m $#,-2>.'!-1m #,m 20#1m #12"'-1m "'12',2-1m "#m !0#!'+'#,2-mm.02'0m"#mJFFm$+'*'1mH[m#12"'-m"#m.*9,23*Zm"#m.*,2m"3*2m7m"#m$032-Ym ,m *1m 20#1m #2.1m 1#m &,m "#1!0'2-m 7m !2*-%"-m 40'!'-,#1m $#,-2>.'!1m /3#m ,-m & >,m 1'"-m "#1!0'21m !-,m ,2#0'-0'""m #,m #12m #1.#!'#Ym 12#m .3#"#m 1#0m 3,m ','!'-m .0m "'1#@0m 3,m 1#m "#m "2-1m +91m !-+.*#(m 7m #1.#!>$'!m !-,(3,2+#,2#m !-,m *1m .- *!'-,#1m "#m m"#m+#*A,m"#100-**"1m.-12#0'-0+#,2#mm#12#m20 (-Ym m GOFm GOGm O #&#)!, 7m (!+(.&0 %; T m %3"#*-j-+#0-Zm YZm 0 -,#**Zm YZm "#m *m %*#1'Zm YZm 00#0Zm YZm -"0'%-Zm Ym 7m !-*Ym ^HFFN_Ym e&,%#1m ',m 2&#m %#,#m #6.0#11'-,m .0-$'*#m -$m 0 '"-.1'1m 2&*',m $2#0m ',$#!2'-,m5'2&m- !!-m#2!&m4'031Yem'0-*m mK[mOHYm m )1)j#,,#"7ZmYZm-+'2mZmYZ830ZmYm^HFFJ_Yme$$'!'#,2m.*,2m0#%#,#02'-,m ,"m %0- !2#0'3+j+#"'2#1m 20,1$-0+2'-,m 4'm 1-+2'!m #+ 07-%#,#1'1m m ',m +#*-,m ^3!3+'1m+#*-mY_Yem*,2m!'#,!#m*1#4'#0mGLL^I_[mMLIjMLOYm m *j '*'m YZm 023,%Zm Ym ^GOOO_Ym em -"3*2#1m #4#*1m -$m 0-2#,-%#,'!m 0-2#',1m ,"m 2&#'0m +1m ,"m $$#!21m 0-2#,-'"m ,"m m -,2#,2m 1m 5#**m 1m &0-+-.*12m203!230#m',m0!'1131m.1#3"-,0!'1131m*-5#01Yem*,2m'-*-%7mG^L_[mLFMj LGHYm m **0"Zm YYm ^GOOO_Ym e0',!'.*#1m -$m *,2m 0##"',%Yem 0',2#"m 7m -&,m '*#7m Xm -,1Zm,!Ym m ,ZmYZm0)ZmYZm #-,%ZmYYZm##ZmYYZm,%ZmYYm7m!-*Ym^HFFI_Yme#,#02'-,m,"m ,*71'1m-$m#,"m1#/3#,!#m"2 1#m$-0mjm2%%',%m*',#1m',m0'!#Yem*,2m&71'-*mGII^J_[m HFJFjMYm m 03+3%,2&,Zm Ym ^GOOG_Ym e3!*#0m m !-,2#,2m -$m 1-+#m '+.-02,2m .*,2m 1.#!'#1Yem*,2m-*m'-m#.mO[mHGGjHGKYm m 1&0$Zm YZm 07Zm Ym ^GOOI_Ym em 17,2&#1'1m ',m -1+-.0'+#"m *##)m ^**'3+m .-003+mY_m1##"1m,"m#4'"#,!#m$-0m0#.'0m,"m0#.*'!2'-,Yem##"m!'#,!#m#1#0!&mI^GKj HI_Ym m 3#0 !&ZmYZm- 1-,Zm YYm^GOJL_Yme&#+'!*m.0-"3!2'-,m-$m+322'-,1Yem230#m GKM[mIFHYm m -!&Z Ym 7m -,1Zm Ym ^HFGF_Ym e,2&-+-,1m 401Im $+'*7j27.#m m #$$#!2-01[m '1!-4#07m,"m$3,!2'-,Ym,,3Y#4m&72-YmJN[mJGOjJILYm m *2'+-0#Zm YZm +-*#0Zm Ym ^GOMG_Ym e0'+#0m 0#/3'0#+#,2m ,"m 2#+.*2#m 1.#!'$'!'27m -$m2&#mm.-*7+#01#m-$mm23+-0m4'031#1Yem0-!m2*m!"m!'mmmmLN^M_[mGKFMj GGYm m 0)*#7ZmYYZm,%ZmYYm^HFFN_Yme..*'!2'-,m-$mm,"m!-m1m #4#01#m#,#2'!m..0-!&#1m2-m*3!'"2#m2&#m3,!2'-,m-$m#,#1m',m*,21m,"m,'+*1Yem 300m#,-+'!1mO^J_[mHGHjHLYm m 0,#1ZmYYm^GOOJ_Ymem+.*'$'!2'-,m-$m3.m2-mIKj) mm5'2&m&'%&m$'"#*'27m ,"m&'%&m7'#*"m$0-+m*+ "m !2#0'-.&%#m2#+.*2#1Yem0-!m2*m!"m!'mmmmOG^L_[m HHGLjHHHFYm m 02*#7ZmYYZm!-*,')ZmYYZm#7#0ZmYm^GOOO_Yme5-m0 '"-.1'1m2&*',m!0-2#,#m "#12301#1Zm .&72-#,#m "#12301#m ,"m 8#2j!0-2#,#m "#12301#Zm #6.0#11#"m ',m 1!&#0'!&'m !-*'Zm !2*78#m m .-*7j!'1m .2&57m 2-m 7'#*"m .0-j*7!-.#,#Yem 30m m '-!&#+m HKO^GjH_[mIOLjJFIYm m GOHm #&#)!, 7O m m 3"0!!-j0,1ZmYZm'202ZmYm^GOOL_Ymem%#,#2'!m+.m-$m+#*-,m^3!3+'1m+#*-m Y_m 5'2&m Zm Zm '1-87+#Zm "'1#1#m 0#1'1'2#,!#m ,"m +-0.&-*-%'!*m +0)#1Yem &#-0m ..*m#,#2mOI[mKMjLJYm m #!)#0Zm YZm -1Zm YZm 3'.#0Zm YZm *+','Zm YZm #3,Zm Ym ^GOOK_Ym e-+ ',#"m +..',%m-$mm,"mm+0)#01m',m 0*#7Yem-*m#,m#,#2mHJO^G_[mLKjMIYm m #,2Zm YYm ^GOOL_Ym e*,2m '1#1#m #1'12,!#m #,#1[m 3,!2'-,m ##21m 203!230#Yem *,2m#**mN^GF_[mGMKMjGMMGYm m #,2*#7Zm YZm !#,,,Zm ^HFFF_Ym e0%#2#"m 0#!-4#07m -$m +322'-,1m ',m 0-1-.&'*Yem#,#2'!1mGKL^I_[mGGLOjGGMIYm m '0, -'+Zm YYZm -*7Zm Ym ^GOMO_Ym em 0.'"m *)*',#m #620!2'-,m .0-!#"30#m $-0m 1!0##,',%m0#!-+ ',,2m.*1+'"mYem3!*#'!m!'"1m#1mM^L_[mGKGIjHIYm m *,!Zm YZm ,'80#1Zm YZm -'%Zm YZm '01-*-Zm YZm 3#8Zm Ym 7m !-*Ym ^HFGG_m e0,1!0'.2-+#m !&0!2#0'82'-,m ,"m &'%&m 2&0-3%&.32m 1m ,"m 1m "'1!-4#07m ',m 3!30 '2m.#.-m^3!30 '2!##_Yemm#,-+'!1mGH[mGFJYm m *,!m Zm@'80#1m Zm-'%mZm'01-*-mZm3#8mZm'!AmYm^HFGG_Yme0,1!0'.2-+#m !&0!2#0'82'-,m ,"m &'%&m 2&0-3%&.32m 1m ,"m 1m "'1!-4#07m ',m 3!30 '2m .#.-m ^3!30 '2!##_Yemm#,-+'!1YmGH[GFJYm m *,!Zm YZm 12#01Zm YZm '01-*-Zm YZm <0#8Zm YZm #0,:m "#8j#"0-1Zm YZm 7m !-*Ym ^HFGH_Ym e0,1!0'.2-+#m 1#/3#,!',%m $-0m m "'1!-4#07m !0-11m 3!3+'1m +#*-eYm m #,-+'!1mGI[HNFYm m *##!)#0Zm YYm ^GOOO_Ym e2&7*#,#m .#0!#.2'-,m ,"m 1'%,*',%[m ,m #4-*32'-,07m .#01.#!2'4#Yem0#,"1m*,2m!'mJ^M_[mHLOjHMJYm m *##!)#0Zm YYZm #,"#Zm Ym ^HFFF_Ym e2&7*#,#[m m %1#-31m 1'%,*m +-*#!3*#m ',m .*,21Yem,,3m#4m#**m#4m'-*mGL[mGjGNYm m -&,j-301#3ZmYm^HFGF_Yme36',[mm+(-0m0#%3*2-0m-$m-0%,-%#,#1'1Yemmm'-*m III^J_[mHOFjLYm m -,-Zm YZm 388-Zm YZm * #%%','Zm YZm '88-Zm YZm 0,!-$-,2#Zm Ym 7m !-*Ym ^HFGG_Ym e#,#2'!m1!0##,',%m-$m 07m.2'#,21m5'2&m!-m,"mm2#!&,-*-%7Yemm#1m -2#1mJ[mIHIYm m -0#4'28Zm YYZm',%ZmYZm*-3$$#ZmYZm&,%ZmYYZm&3ZmYm7m!-*Ym^HFFI_Yme0%#j 1!*#m'"#,2'$'!2'-,m-$m1',%*#j$#230#m.-*7+-0.&'1+1m',m!-+.*#6m%#,-+#1Yem#,-+#m#1m GI^I_[mKGIjHIYm m -3*#+Zm YZm #0%,7Zm YZm #0,,"#8Zm YZm 0-"#!Zm YZm 02',Zm Ym 7m !-*Ym ^HFFN_Ym em !-,1#04#"m +322'-,m ',m ,m #2&7*#,#m '-17,2&#1'1m #,87+#m *#"1m 2-m ,"0-+-,-#!7m ',m +#*-,1Yem!'#,!#mIHG^KNOF_[mNILjNYm m 0,"5%2ZmYYZm,#..#01ZmY YZm'()+.ZmY YZm'**#Zm Ym^HFFH_Yme4#0#6.0#11'-,m -$m2&#m2-+2-m1!jGm%#,#m+#"'2#1m&'%&m',1#,1'2'4'27m2-mm2-6',1m,"m$3+-,'1',mGm',m 2-+2-m &'07m 0--21m ,"m !-,$#01m 0#1'12,!#m 2-m *2#0,0'm *2#0,2m $Ym 1.Ym *7!-.#01'!'m ',m '!-2',m3+ 02'!m.*,21Yem-*m*,2m'!0- #m,2#0!2mGK^G_[mIKjJHYm m 0--)#1ZmY Ym^GOOO_Yme&#m#11#,!#m-$m1Yem#,#mHIJ^H_[mGMMjGNLYm GOIm O #&#)!, 7m m 0-2+,Zm YZm '* #012#',Zm YZm -4*1)'Zm YZm #0',Zm YZm -%'+-,2Zm Ym 7m !-*Ym ^HFFH_Ym e#1'12,!#m%#,#m&-+-*-%3#1m',m+#*-,m0#m*',)#"m2-m%#,#2'!m*-!'m!-,$#00',%m"'1#1#m,"m .#12m0#1'12,!#Yem&#-0m..*m#,#2mGFJ^LjM_[mGFKKjGFLIYm m 0-5,',%Zm YYZm # 12#0Zm YZm - #021Zm YYZm 4#*Zm YYm ^GOOH_Ym e"#,2'$'!2'-,m -$m ,m'1-87+#m$-0+m-$m.0-2#',m17,2&#1'1m','2'2'-,m$!2-0mJm',m.*,21Yem m'-*m&#+mHLM^GJ_[m GFFOLjGFFYm m m 03%%#+,,Zm YZm ,"5#0%#0Zm YZm 11#6Zm YZm 2-08Zm Ym ^GOOL_Ym e,*71'1m -$m $12m ,#320-,j%#,#02#"m+32,21m2m2&#m0 '"-.1'1m2&*',mJm*-!31Yem*,2m mGF^J_[mMKKjLFYm m 03++#**ZmYYZm0.12#0ZmYYm^HFFG_Yme#**m5**m+#2 -*'1+m',m$03'2m1-$2#,',%m ,"m/3*'27m,"m'21m+,'.3*2'-,m',m20,1%#,'!m.*,21Yem*,2m-*m'-*mJM^GjH_[mIGGjJFYm m 3"'+,Zm YYZm -Zm YZm --"Zm YYZm ',%Zm YYm ^HFFF_Ym em "##.j!-4#0%#m 2-+2-m m *' 007m ,"m .0-1.#!21m 2-50"m "#4#*-.+#,2m -$m ,m m $0+#5-0)m $-0m %#,-+#m1#/3#,!',%Yem#,-+#m#1mGF^G_[mGHOjILYm m 3*-5Zm YZm !&',"*#0Zm YZm &-'Zm YZm #&*Zm Ym ^HFFJ_Ym e2&-*,2[m m "2 1#m -,m .*,2j.2&-%#,m',2#0!2'-,1Yem,m'*'!-m'-*mJ^J_[mKHOjILYm m 31!&%#1ZmYZm-**0'!&#0ZmYZm,1203%ZmYZm'+-,1ZmYZm-*2#0ZmYm7m!-*Ym^GOOM_Ym e&#m 0*#7m*-m%#,#[mm,-4#*m!-,20-*m#*#+#,2m-$m.*,2m.2&-%#,m0#1'12,!#Yem#**mNN^K_[m LOKjMFKYm m 31&Zm YYZm 071,Zm Y Ym ^HFGF_Ym e'[m m .#01-,*'8#"m ..0-!&m 2-m 2&#m '"#,2'$'!2'-,m-$m',"3!#"m+322'-,1m',m0 '"-.1'1Yem*,2m&71'-*mGKJ^G_[mHKjIKYm m *"5#**ZmYYZm!**3+ZmYZm&5ZmYZm3#&* 3#0ZmY YZm01&**ZmYYm7m!-*Ym ^HFFJ_Ym em 1203!230#"m +32,2m .-.3*2'-,m $-0m $-050"m ,"m 0#4#01#m %#,#2'!1m ',m 0*#7m ^-0"#3+m43*%0#mY_Yem&#m*,2m -30,*mJF^G_[mGJIjGKFYm m 0-*Zm YZm 3,28Zm Ym ^HFFG_Ym em .*12'"m 2#0+',*m -6'"1#m !-+#1m 2-m *'%&2[m '+.*'!2'-,1m$-0m!0-2#,-'"m '-17,2&#1'1m,"m!&*-0-0#1.'02'-,Yem0#,"1m*,2m!'mL[mIGj ILYm m 12%,Zm YZm "#0*'Zm YZm 1/3*','Zm YZm #,13*'j-"'Zm YZm *",Zm Ym 7m !-*Ym ^HFFM_Yme&#m2-+2-m#2&7*#,#m0#!#.2-0mjIm^_m'1m,-2m',4-*4#"m',m+#"'2',%m-8-,#m 1#,1'2'4'27[m !31*m 0#*2'-,1&'.1m +-,%m #2&7*#,#m #+'11'-,Zm -6'"2'4#m 3012m ,"m 2'113#m "+%#Yem#5m&72-*mGMJ^H_[mIJHjKLYm m #!!&','ZmYZm3**'%,ZmY YZm-4#7ZmYYZm'*,#0Zm Y Ym^GOON_Yme&0!2#0'82'-,m-$m %++m '00"'2'-,j',"3!#"m "#*#2'-,m +322'-,1m 2m m 1#*#!2 *#m *-!31m ',m 0 '"-.1'1Yem 322m#1mJFG^GjH_[mGOOjHFLYm m #0+)Zm YZm -7*#Zm YZm &012',Zm m YZm '%Zm YZm &,%Zm YZm !&+'"2Zm YZm 7m !-*Ym ^HFGG_Ym $$'!'#,2m "#1'%,m ,"m 11#+ *7m -$m !312-+m m ,"m -2&#0m m #$$#!2-0j 1#"m !-,1203!21m$-0mm20%#2',%Ym3!*#'!m!'"1m#1#0!&mIO[NHYm m &)04-027Zm YZm 031-4Zm YZm -2#**Zm YYm ^HFGG_Ym e'2#j"'0#!2#"m +32%#,#1'1m -$m 2&#m 0 '"-.1'1m&#2#0-20'+#0'!mm.0-2#',m #2m 13 3,'2m 13%%#121m "'4#0%#,2m +#!&,'1+1m -$m#$$#!2-0m!2'42'-,m #25##,m.*,2m,"m,'+*mm.0-2#',1Yem*,2mHIK^I_[mLGKjHMYm GOJm #&#)!, 7O m m &,%Zm YZm 5-)Zm YYZm *##!)#0Zm YYZm #7#0-5'28Zm YYm ^GOOI_Ym e0 '"-.1'1m #2&7*#,#j0#1.-,1#m %#,#m G[m 1'+'*0'27m -$m .0-"3!2m 2-m 25-j!-+.-,#,2m 0#%3*2-01Yem !'#,!#mHLH^KGII_[mKIOjJJYm m &5"#Zm YZm ')-0Zm YZm 032'%+Zm YZm 011-,Zm YZm '4#),,"Zm Ym 7m !-*Ym ^HFGF_Ym e#4#*-.+#,2m ,"m !&0!2#0'82'-,m -$m ,m -2m j.-.3*2'-,m ,"m '"#,2'$'!2'-,m -$m +322'-,1m ',m *'%,',m ,"m #2j%*3!,m '-17,2&#1'1m %#,#1Yem m *,2m '-*mGF[mNLYm m &#,Zm YYZm **'#Zm YYm ^HFGF_Ym e,*71'1m -$m 2&#m $3,!2'-,*m !-,1#042'-,m -$m #2&7*#,#m0#!#.2-01m #25##,m+'8#m,"m0 '"-.1'1Yem*,2m-*m'-*mMJ^JjK_[mJFKjHGYm m &'1&-*+Zm YYZm -)#0Zm YZm 7Zm YZ21)5'!8Zm Y Ym ^HFFL_Ym e-12j+'!0- #m ',2#0!2'-,1[m1&.',%m2&#m#4-*32'-,m-$m2&#m.*,2m'++3,#m0#1.-,1#Yem#**mGHJ^J_[mNFIjGJYm m &-'Zm YYZm 72#,Zm YYZm 23)3+**'Zm YYZm -,%Zm YZm &)7Zm YYm 7m !-*Ym ^HFFM_Ym em 1-7 #,m 20,1!0'.2m +.[m %#,#m "'120' 32'-,Zm &.*-27.#m ,"m 1',%*#j,3!*#-2'"#m .-*7+-0.&'1+m,*71'1Yem#,#2'!1mGML^G_[mLNKjOLYm m &-4#*-,Zm YZm #12'#0Zm YZm '-4',88-Zm YZm -%'+-,2Zm YZm 00-3$Zm Ym ^HFGG_Ym e'12-*-%'!*m 123"7m -$m -0%,-%#,#1'1m ',m 3!3+'1m +#*-m Ym $2#0m %#,#2'!m 20,1$-0+2'-,[m 5&7m'1m'2m"'$$'!3*2m2-m- 2',m20,1%#,'!m.*,21]em*,2m#**m#.mIF^GG_[mHFFGjGGYm m *0)Zm YYZm 071,Zm Y Ym ^HFFM_Ym e0-2-!-*[m ,m '+.0-4#"m &'%&j2&0-3%&.32m +#2&-"m $-0m %#,#02',%m 2'113#m 1+.*#1m ',m OLj5#**m $-0+2m $-0m .*,2m %#,-27.',%m ^!#j.m HYF_Yem*,2m#2&-"1mI[mNYm m -* #02ZmYZm'**ZmY YZm-+.ZmYZm#7,-*"1ZmYZm2#',#ZmYYm7m!-*Ym^HFFG_Yme'%&j &0-3%&.32m!0##,',%m$-0m,"3!#"m-',2m322'-,1Yem*,2m&71'-*mGHL[mJNFmjmJNJYm m -**',%#Zm YZm -**#0Zm Ym ^HFFG_Ym e'$$#0#,2'*m ',"3!2'-,m -$m 25-m .-22-m %#,#1Zm 2.06Hm ,"m 2Zm ',m 0#1.-,1#m 2-m ',$#!2'-,m 7m &72-.&2&-0m ',$#12,1m ,"m 2-m 5-3,"',%Yem*,2m-*m'-*mJL^K_[mKHGjOYm m -+'Zm YZm #,')-$$Zm Ym ^HFFL_Ym e[m .0!2'!*m 1',%*#j,3!*#-2'"#m +322'-,m "'1!-4#07Yem*,2m mJK^J_[mLNJjOJYm m -+'Zm YZm -3,%Zm YZm '**Zm Y YZm #7,-*"1Zm YYZm 0##,#Zm YYm 7m !-*Ym ^HFFJ_Ym e$$'!'#,2m"'1!-4#07m-$mm.-*7+-0.&'1+1m',m,230*m.-.3*2'-,1m 7m!-2'**',%Yem*,2m mIM^K_[mMMNjNLYm m --.#0Zm YYZm '**Zm Y YZm .-02Zm YYZm 0*-5Zm YYZm *#$$,#0Zm YYm 7m !-*Ym ^HFFN_Ym e 2-m"#2#!2m',"3!#"m+322'-,1m',m1-7 #,Yemm*,2m'-*mN[mOYm -0 !&-Zm YZm -+-(0-Zm YZm #!&Zm jYZm 2!&<Zm YZm -+#8j '+#,#8Zm Ym ^HFGI_Ym e0,1!0'.2-+'!m 4#,21m ,4-*4#"m ',m #*-,m 230#j03'2m 1!'11'-,m -+.0'1#m 2&#m #/3#,2'*m ,"3!2'-,m -$m #**j**m #%0"',%m #,#1m -3.*#"m 2-m m 2'+3*2'-,m -$m ,"-m ,"m6-!72-1'1eYm-mmN^I_[m#KNILIYm mm &+,'j0"1Zm YZm 0-"#!Zm YZm -3*#+Zm YZm #4#/3#Zm YZm *1"-,Zm YYm 7m !-*Ym ^HFGF_Ym e,%',##0',%m #*-,m *,21m 5'2&m +.0-4#"m 03'2m &#*$m '$#m 1',%m 2&#m m..0-!&Yem-m,#mK^GH_[m#GKMMLYm GOKm O #&#)!, 7m m *+'1Zm YZm !&+'"2Zm YZm #m '%,-0Zm YZm -3117Zm YZm 3012',Zm Ym 7m !-*Ym ^HFFN_Ym e" Zm m '13+m 12'43+m ',m 1'*'!-m $-050"m ,"m 0#4#01#m %#,#2'!1m 2--*Yem #,-+#m '-*m O^H_[mJIYm m ,',j-*#%Zm YZm #'1Zm YZm 3"0!!-j0,1Zm YZm '202Zm YZm 23 Zm YYm 7m !-*Ym ^HFFF_Ym e'+.*#m 1#/3#,!#m 0#.#21m ',m 3!3+'1m +..',%m ,"m +.m +#0%',%Yem #,-+#m JI^L_[mOLIjMJYm m #*#3ZmYZm-,89*#8ZmYZm-,$-02ZmYZm#,"&+,#ZmYZm3'%"-+#,#!&ZmYm7m!-*Ym ^HFFM_Yme203!230#m-$m25-m+#*-,m0#%'-,1m0#4#*1m&'%&m+'!0-17,2#,7m5'2&m1#/3#,!#"m.*,2m 1.#!'#1Yem-*m#,#2m#,-+'!1mHMN^L_[mLGGjHHYm m #*#3Zm YZm 12#01Zm YZm -'%Zm YZm -,89*#8j-Zm YZm #0,9,"#8j'*4Zm Ym 7m !-*Ym ^HFFO_Ym em 1#2m -$m j1m $-0m +.m 12302'-,m ,"m !3*2'40m '"#,2'$'!2'-,m ',m +#*-,Yem m*,2m'-*mO[mOFYm m #,,7Zm YYm ^GOOK_Ym e,4-*4#+#,2m -$m !2#0'*m .-*71!!&0'"#1m ',m .*,2m .2&-%#,#1'1Yem,,3m#4m&72-.2&-*mII[mGMIjOMYm m '8Zm YZm #0%,7Zm YZm -0+'1,-Zm YZm '01-*-Zm YZm *,!Zm Ym 7m !-*Ym ^HFGG_Ym em !-,1#,131m*',)%#m+.m$-0m+-*#!3*0m+0)#01m,"m/3,2'22'4#m20'2m*-!'m11-!'2#"m5'2&m #!-,-+'!**7m'+.-02,2m20'21m',m+#*-,m^3!3+'1m+#*-mY_Yemm*,2m'-*mGG[mGGGYm m '8Zm YZm 30"7Zm YZm &0'12Zm YZm -0-2j3"07Zm YYZm ',%*#0Zm Ym 7m !-*Ym ^HFFK_Ym e&0!2#0'82'-,m-$m+0)#01m2-m"#2#0+',#m2&#m#62#,2m,"m40' '*'27m-$m*#$m1#,#1!#,!#m ',m0 '"-.1'1Ymm+#2 -*'!m.0-$'*',%m..0-!&Yem*,2m&71'-*mGIN^H_[mNONjOFNYm m -"%1-,Zm YYZm#**1ZmYYm^GOMM_Yme!2'-,m-$m1',%*#j120,"m1.#!'$'!m,3!*#1#1m-,m +-"#*mm&#2#0-"3.*#6#1m-$m"#$',#"m1'8#m,"m1#/3#,!#Yem'-!&#+'1207mGL^GG_[mHIMJjOYm m -,%Zm YZm ',!#,2Zm YZ&0.Zm Ym ^HFFO_Ym e'+3*2,#-31m +322'-,m "#2#!2'-,m -$m 2&0##m&-+-#-*-%-31m%#,#1m',m5&#2m 7m'%&m#1-*32'-,m#*2',%m,*71'1m,"m322'-,m 304#7-0Yemm*,2m'-*mO[mGJIYm m -7*#Zm YZm-7*#Zm Ym^GOOF_Yme1-*2'-,m-$m.*,2mm$0-+m$0#1&m2'113#Yem-!31mGH[m GIjGKYm m 0.#0Zm YYZm !**3+Zm YYZm 2-32Zm YYZm *"#Zm Y YZ-#,1Zm YYm ^HFFJ_Ym em &'%&j2&0-3%&.32m +#2&-"m $-0m '"#,2'$7',%m j#2&7*jj,'20-1-30#m ^_j',"3!#"m .-',2m +322'-,1m',m8# 0$'1&Yem#2&-"1m#**m'-*mMM[mOGjGGHYm m m -,1-02'3+m ^HFFJ_Ym e&#m m ^7!*-.#"'m $m m *#+#,21_m0-(#!2Yem!'#,!#mIFL^KLOL_[mLILjJFYm m 830m Zm 3&1&'Zm YZm 132m Ym ^HFFF_Ym e$$#!2m -$m #2&7*#,#m -,m %0- !2#0'3+m 23+#$!'#,1j+#"'2#"m%#,#m20,1$#0m2-m+#*-,Yem*,2m0##"mGGO[mMKjMOYm m ,%Zm YZm 03+#2Zm Ym ^GOOF_Ym e%0- !2#0'3+m 23+#$!'#,1m +#"'2#"m 20,1$-0+2'-,m,"m0#%#,#02'-,m-$m+31)+#*-,m.*,21Yem*,2m#**m#.mO[mGLFjGLJYm m #0,9,"#8j.0'!'-m ^HFGF_Ym e01'2'!m .*,2m ',$#!2'-,m '1m .02'**7m !-,20-**#"m 2&0-3%&m17+ '-2'!m.2&571Yem##"m#1#0!&mKF[mGYm m #0,,"#8j'*4ZmYZm"30"-ZmYZm*,!Zm YZm12#01ZmYZm'!-ZmYm7m!-*Ym^HFFN_Yme',m +..',%m-$m%#,-+'!m,"mj"#0'4#"m 1m ',m +#*-,m ^3!3+'1m +#*-mY_Yem &#-0m ..*m #,#2mGGN^G_[mGIOjKFYm GOLm #&#)!, 7O m m *-0Zm YYm ^GOMG_Ym e300#,2m 12231m %#,#j$-0j%#,#m !-,!#.2Yem ,,Ym #4Ym &72-.2&-*YmO[mHMKjHOLYm m *-0#1Zm YZm *m &7-3'Zm YZm "#m '**#0 #!)Zm YZm -+-(0-Zm YZm 2!&#Zm Ym 7m !-*Ym ^HFFH_Yme-*#m-$m#2&7*#,#m',m2&#m '-17,2&#2'!m.2&57m-$m*'.&2'!m#12#0m0-+m4-*2'*#1m',m &0#,2'1m,2*-3.#m+#*-,1Yem m6.m-2mKI^ILM_[mHFGjLYm m *-0#1Zm YYm ^HFFG_Ym '1'-*-%>m 7m +"30!'A,m "#*m +#*A,m ,2*-3.#m &0#,2'1m !-,m 3,m %#,m ,2'1#,2'"-m "#m *m #,8'+m m -6'"1Ym Ym #1'1Zm ,'4#01'""m "#m 30!'Ym 30!'Ym m 01#0m^GONL_Yme#,#1m$-0m0#1'12,!#m2-m.*,2m4'031#1Yemm02'Ym#4Ym*,2m!'Y[m HKMjHOJYm m 3Zm YYZm &3Zm YYZm &3Zm YYZm ',%Zm YYZm 3-Zm YYm ^HFFK_Ym e'031j',"3!#"m %#,#m1'*#,!',%m',m2-+2-m$03'2Yem*,2m mJI^H_[mHOOjIFNYm m 3&0+,,Zm YZm #02#*Zm YZm #02&-*"Zm YZm #%#+,,Zm Ym ^HFFK_Ym e#+-4*m -$m +'1+2!&#"m 1#1m $0-+m 17,2&#2'!m %#,#1m 7m #,87+2'!m +'1+2!&m !*#4%#Yem 3!*#'!m !'"1m#1mII^L_[m#KNYm m "7ZmYYZm#0+,1ZmYYZm,m"#m*ZmYYZm,m--ZmYYZm'11#0ZmYYm7m!-*Ym ^HFFO_Ym e+.*#+#,22'-,m -$m 25-m &'%&m 2&0-3%&j.32m 2#!&,'/3#1m ',m m ,-4#*m ..*'!2'-,[m "#2#!2',%m .-',2m +322'-,1m ',m *0%#m m +322#"m .*,2m .-.3*2'-,1Yem *,2m #2&-"1m K[m GIYm m + *#ZmYYZm--,$'#*"ZmYYZm!&**#0ZmYYm^GOON_Yme'12'"',#m)',1#m!2'4'27m-$m 2&#mGm#2&7*#,#m0#!#.2-0m$0-+m0 '"-.1'1Yem0-!m2*m!"m!'mmmmOK^GI_[mMNHKjOYm m + *#ZmYYZm3ZmYZ!&**#0ZmYYm^HFFH_Yme322'-,*m,*71'1m-$m2&#m#2&7*#,#m 0#!#.2-0mGYm-*#m-$m2&#m&'12'"',#m)',1#m"-+',m',m"-+',,2m#2&7*#,#m',1#,1'2'4'27Yem *,2m&71'-*mGHN^J_[mGJHNjINYm m -ZmYZm -&,1#,ZmYZm7#01ZmYZm&-+1ZmYYZm-#*m**'1ZmYYm7m!-*Ym^HFFJ_Yme&#m .-274'031m 0#!#11'4#m 0#1'12,!#m %#,#Zm 1 +GZm '"#,2'$'#1m m ,-4#*m 0-*#m $-0m 20,1*2'-,m ','2'2'-,m$!2-0m#Jm',m!#**j2-j!#**m20$$'!)',%Yem*,2m mJF^I_[mIMLjNKYm m 0!'j1m Zm *'4#0Zm YZm A+#8m m 7m '!#,2#m m ^HFFF_Ym eZm m ,"m m+0)#01m2-m+#130#m%#,#2'!m"'4#01'27m',m+#*-,Yem&#-0m..*m#,#2mGFG[mNLFjNLJYm m 0!'j1Zm YZm#,()ZmYZm,1#4#0',-ZmYZm-30%#-'1ZmYZm'0ZmYm7m!-*Ym^HFGH_Ym e&#m%#,-+#m-$m+#*-,m^3!3+'1m+#*-mY_Yem0-!m2*m!"m!'mmmmGFO^HO_[mGGNMHjMYm m #,0"Zm YZm -3 *#Zm Ym ^HFFK_Ym eYm m 2&#-07m -$m $03'2m !*'+!2#0'!m #2&7*#,#m #+'11'-,Yem*,2m&71'-*mGIO^G_[mKIGjJKYm m #.21m ^HFFH_Ym em !-+.0'1-,m #25##,m 0-.m -+#12'!2'-,Zm *11'!*m *,2m 0##"',%m,"m#,#2'!m,%',##0',%YemmJH^L_[mGMNFjGMOFYm m '*!&0'12ZmY YZm3%&,ZmYYm^HFFK_Ymem5'2&-32mm.*-3%&[mm,#5m+#2&-"m 5'2&m..*'!2'-,1m$-0m0#4#01#m%#,#2'!1Yem300#,2m.','-,m',m*,2m'-*-%7mN[mHGGmjmHGKYm m '*!&0'12ZmYZmd#'*ZmYZm-1#ZmYZm#2)ZmYZm3%&,ZmYm^HFFL_Ymem'1m,m #$$#!2'4#m 0#4#01#m %#,#2'!1m 2#!&,'/3#m $-0m #,-0& "'2'1m #*#%,1Yem m #,-+'!1m M^G_[m HLHYm m GOMm O #&#)!, 7m m ',%01ZmYYZm3%&2ZmYZm-,#, #0%ZmYm^GOOO_Yme#Jm','2'2'-,m$!2-01[m#$$#!2-01m -$m+m0#!03'2+#,2m2-m0' -1-+#1m,"m0#%3*2-01m-$m20,1*2'-,Yem,,3m#4m'-!&#+m LN[mOGIjLIYm m '-4,,-,'Zm Ym ^HFFG_Ym e-*#!3*0m '-*-%7m -$m 03'2m 2302'-,m ,"m '.#,',%Yem ,,3m#4m*,2m&71'-*m*,2m-*m'-*mKH[mMHKjMJOYm m '-4,,-,'Zm Ym ^HFFM_Ym e03'2m 0'.#,',%m +32,21m 7'#*"m ',1'%&21m ',2-m 0'.#,',%m !-,20-*Yem300m.',m*,2m'-*mGF^I_[mHNIjOYm m '3*',-Zm YZm 02*#7Zm YYZm !-*,')Zm YYm ^GOOI_Ym e#%3*2'-,m -$m !0-2#,-'"m '-17,2&#1'1m"30',%m2-+2-m"#4#*-.+#,2Yem*,2m#**mK^J_[mIMOjNMYm m -,89*#8ZmYYZm#,()ZmYZm#,$$ZmYYZm'0ZmYZm1!3 #02Zm YYm7m!-*Ym^HFGFm _Ym e#/3#,!',%m -$m LYMm m -$m 2&#m +#*-,m %#,-+#m 31',%m m m .--*',%m 1202#%7Yem m *,2m'-*mGF[mHJLYm m -,89*#8Zm YYZm 0!'j1Zm YZm 0B1Zm YZm 3'%"-+#,#!&Zm Ym ^HFGFm _Ym e#,#02'-,m -$m m j 1#"m .&71'!*m +.m -$m 2&#m +#*-,m %#,-+#Yem m #,-+'!1m GG[m IIOYm m m -,89*#8j #1Zm YZm *,!Zm YZm -'%Zm YZm -,8*#8j-Zm YZm '!-Zm Ym 7m !-*Ym ^HFFM_Ym e[m,mm"2 1#m$-0m+#*-,m$3,!2'-,*m%#,-+'!1Yemm#,-+'!1mN[mIFLYm m -,8*#8j #1Zm YZm ,'80#1Zm YZm 0,"Zm YYm ^HFGH_Ym e'!0-007m ,*71'1m 1&-51m2&2m0#!#11'4#m0#1'12,!#m2-m2#0+#*-,m+-1'!m4'031m',m+#*-,m'1m11-!'2#"m5'2&m 2&#m',"3!2'-,m-$m"#$#,1#m0#1.-,1#m%#,#1Yem-*m*,2m'!0- #m,2#0!2mHK^G_[mGFMjGNYm m -,89*#8j-Zm YZm 3Zm YZm 12#01Zm YZm -'%Zm YZm -,$-02#Zm Y Ym 7m !-*Ym ^HFGG_Ym e-50"1m m m .*2$-0+m $-0m $3,!2'-,*m %#,-+'!1m ',m '#*m "#m .-m +#*-,1Yem m #1m-2#1mJ[mHNOYm m -,8*-ZmY YZm*'4#0ZmYZm0!'j1Zm YZm-,$-02ZmYZm-*!#2j,(3,ZmYm7m!-*Ym ^HFFK_Ym e'+.*#j1#/3#,!#m 0#.#2m +0)#01m 31#"m ',m +#0%',%m *',)%#m +.1m -$m +#*-,m ^3!3+'1m+#*-mY_Yem&#-0m..*m#,#2mGGF^K_[mNFHjGGYm m 0##, #0%Zm YYZ-Zm Ym ^HFFJ_Ym e&#m 0-*#m ,"m 0#%3*2'-,m -$m .0-%0++#"m !#**m "#2&m',m.*,2j.2&-%#,m',2#0!2'-,1Yem#**m'!0- '-*mL^I_[mHFGjGGYm m 0##,#ZmYYZm-"-+-ZmYYZm7*-0ZmYYZm#,')-$$Zm YYZm'**ZmY Ym7m!-*Ym^HFFI_Ym e.#!203+m-$m!&#+'!**7m',"3!#"m+322'-,1m$0-+mm*0%#j1!*#m0#4#01#j%#,#2'!m1!0##,m',m 0 '"-.1'1Yem#,#2'!1mGLJ^H_[mMIGjJFYm m 0-2#5-*"ZmYm^HFFL_Yme&#m%#,#2'!1m,"m '-!&#+'1207m-$m$*-0*m.'%+#,21Yem,,3m #4m*,2m'-*mKM[mMLGjNFYm m 03#, 3+Zm YZm 4#&j,7Zm YZm #"0Zm YZ8',Zm Ym ^GONG_Ym e#/3#,!#m 1.#!'$'!'27m-$m+#2&7*2'-,m',m&'%&#0m.*,2mYem230#mHOH^KNHL_[mNLFjHYm m 3'1m Zm -31,Zm YZm -%'+-,2Zm YZm '202Zm YZm #!&Zm Ym ^GOON_Ym e#*-,m '-2#!&,-*-%7Yem'-2#!&,-*m#,2m,%m#4mGK[mHNOjIGGYm m 38+,ZmYZm!)#0Zm YYm^GOOF_Yme6.*-'2',%m2&#m20'.*#m0#1.-,1#m-$m0 '"-.1'1m2-m '"#,2'$7m#2&7*#,#j0#*2#"m+32,21Yem*,2m#**mH^L_[mKGIjHIYm GONm #&#)!, 7O m m +"m YZm #20',-Zm YYZm )3,%Zm Ym ^GONH_Ym em ,-4#*m 0#.#2#"m #*#+#,2m 5'2&m jjm $-0+',%m .-2#,2'*m '1m 5'"#*7m $-3,"m ',m #4-*323-,07m "'4#01#m #3)0'-2'!m %#,-+#1Yem0-!m2*m!"m!'mmmmMO[m[mLJLKjLJLOYm m ,"#*Zm Ym ^GONH_Ym e7,+'!1m -$m %#,#m $*-5m ',m ,m #6.#0'+#,2*m .-.3*2'-,m -$m 3!3+'1m+#*-mem+#0Ym Ym-2mLO^GF_[mGKINjGKJLYm m 1#ZmYZm+-)ZmYZm"ZmYZm'0-'ZmYZm)+-2-ZmYm7m!-*Ym^HFFF_Yme0#m3,"#0m 2&#m .*1+m !-,!#,202'-,j2'+#m !304#m -$m ',-0%,'!m $*3-0'"#m $-**-5',%m 1#4-$*30,#m ,#12&#1'm !-00#*2#1m 5'2&m HGm +m *#4#*m ',m +-,-,3!*#0m !#**1Yem ,#12&#1'-*-%7m OH^L_[mGLLGjLYm m #,')-$$ZmYZm-+'ZmYm^HFFI_Yme',%*#j,3!*#-2'"#m+322'-,1m$-0m.*,2m$3,!2'-,*m %#,-+'!1Yem,,3m#4m*,2m'-*mKJ[mIMKjJFGYm m '0-!&')ZmYZm3'"#0"-,'ZmYZm,ZmYZm1',%ZmYYZm3,ZmYYm7m!-*Ym^HFFJ_Yme'!#m +32,2m0#1-30!#1m$-0m%#,#m"'1!-4#07Yem*,2m-*m'-*mKJ^I_[mIHKjIJYm m '01!& #0%Zm Ym ^HFFG_Ym e0-2#,-'"m '-17,2&#1'1m ',m $*-5#0',%m .*,21Yem 300#,2m .','-,m',m*,2m'-*-%7mJ^I_[mHGFjHGNYm m -1.'2*ZmYm^HFFO_Yme&**#,%#1m$-0m#$$#!2'4#m+0)#0j11'12#"m1#*#!2'-,m',m.*,21Yem #,#2'!mGIL^H_[mIFIjGFYm m 3Zm YZm &,%Zm YZm 3,Zm YZm #7#0-5'28Zm YYm ^GOOK_Ym e2&7*#,#m ',1#,1'2'4'27m !-,$#00#"m 7m0 '"-.1'1mm%#,#Yem!'#,!#mHLO^KHIG_[mGMGHjJYm m #&'1Zm YYZm &'+'83Zm YZm 2-Zm YZm 13"Zm YZm )3+'Zm Ym ^HFGH_Ym e'1!-4#07m -$m '%&j-,$'"#,!#m ',%*#m 3!*#-2'"#m -*7+-0.&'1+1m $0-+m 0%#j!*#m #m -4-m ,*71'1m-$m#$m0,1!0'.21m-$m#%'*-.1m231!&''Zmm'*"m&#2m0-%#,'2-0Yemm#1Ym m 1!1-,Zm YZm -,#,Zm YZm +'0Zm YZm '01!& #0%Zm Ym ^HFFH_Ym e*-,',%m -$m 2,%#0',#m $0-+m 2-+2-m 0#4#*1m m !0-2#,-'"m '1-+#01#m #11#,2'*m $-0m 2&#m .0-"3!2'-,m -$m #2j !0-2#,#m,"m6,2&-.&7**1m',m.*,21Yem*,2m#**mGJ^H_[mIIIjJHYm m 8/3'#0"-Zm Ym ^HFFG_Ym e,%#,'#0>m %#,<2'!m 7m 20,1$#0#,!'m %<,'!eYm "'!'-,#1m '09+'"#mYYm"0'"Ym m #$$0#7Zm Ym ^GOOFY_Ym .>23*-[m ,m -32*',#m !*11'$'!2'-,m -$m 2&#m 3!30 '2!##Ym ,[m 2#1ZmYYZm- ',1-,ZmYYZm #$$0#7ZmYme'-*-%7m,"m32'*'82'-,m-$m2&#m3!30 '2!##eYm 2&!m,"m-,"-,m-0,#**m,'4#01'27[m.YJJOjJLIYmJNK.Ym m -- #30Zm YZm ',%Zm Y YZm -*',Zm Y YZm &-+1Zm YYZm #,Zm YYm ^HFFJ_Ym e&#m 310'3+m 5'*2m 0#1'12,!#m *-!31m -+jHm -$m +#*-,m !-,2',1m m 1',%*#m 0#1'12,!#m %#,#m 5'2&m !-+.*#6m$#230#1Yem*,2m mIO^I_[mHNIjOMYm m 28'0ZmYZm,',j-*#%ZmYZm830'ZmYZm0!&'ZmYm^GOOL_Yme#,%2&m.-*7+-0.&'1+m ,"m&-+-*-%'#1m-$m+'!0-12#**'2#1m',m1#4#0*m3!30 '2!#1m1.#!'#1Yem&#-0m..*m#,#2m OI[mGHNHjGHOFYm m ##,Zm YYm ^GOOF_Ym e#,#j$-0j%#,#m !-+.*#+#,20'27m ',m .*,2j.2&-%#,m ',2#0!2'-,1Yem,,3m#4m#,#2mHJ[mJJMjLIYm m #,"**ZmY YYm^GONN_Yme#,#2'!j40'2'-,m-$m#2&7*#,#m.0-"3!2'-,m',m&04#12#"mm +31)+#*-,m$03'21Yem-02!'#,!#mHI[mMKOjMLGYm GOOm O #&#)!, 7m m *##ZmYZm'#+,YmYm^GOOO_Yme'$$#0#,2'*m6.0#11'-,m-$m5-m-4#*m#+ #01m-$m 2&#m-+2-m2&7*#,#j#!#.2-0m+'*7Yem*,2m&71'-*mGHF[mGLKjGMHYm m ,-**Zm YYZm +-1Zm YYZm #,%Zm YZm -* 0--)Zm YYZm &-5Zm Ym 7m !-*Ym ^HFGG_Ym em$-0m**#0%#,m0#"3!2'-,m,"m'+.0-4#+#,2m-$m/3*'27m20'21m',m.#,32m^0!&'1m &7.-%#mY_Yemm*,2m'-*mGG[mNGYm m -"7+ZmYZm$8ZmYm^HFFI_Yme&71'!*m,"m!&#+'!*m+32%#,#1'1Yem#2&-"1m-*m '-*mHIL[mGNOjHFJYm m -,'#!8,7Zm YZm 313 #*Zm Ym ^GOOI_Ym em .0-!#"30#m $-0m +.',%m 0 '"-.1'1m +322'-,1m 31',%m !-j"-+',,2m #!-27.#j1.#!'$'!m j 1#"m +0)#01Yem *,2m -30,*m J[m JFIjJGFYm m --0,,##$ZmYZm#**#02ZmYYZm,m"#0m##,Zm YYm^GONH_Ymejm,"m0"'2'-,j ',"3!#"m +322'-,m $0#/3#,!'#1m 2m ',"'4'"3*m *-!'m ',m 0 '"-.1'1m 2&*',m ^Y_m #7,&Yem 322m#1mOI^G_[mGFOjHIYm m 071,Zm Ym ^HFFJ_Ym e!#j!.Ym m &'%&j2&0-3%&.32m +#2&-"m $-0m !.230',%m .*,2m 2'113#m1+.*#1m$-0m%#,-27.#m,*71'1Yem*,2m&71'-*mGIK^I_[mGGLHjOYm m 3,%Zm YZm "+, &,Zm YZm 'Zm YZm +#'Zm YZm &1)0Zm YYm 7m !-*Ym ^HFFO_Ym e"#,2'$'!2'-,m -$m +','230#m ',4#02#"j0#.#2m 20,1.-1 *#m #*#+#,21m ^1_m ,"m '-%#,#1'1m -$m 2&#'0m 1'1m ',m 2&#m -*,!##[m ,#5m $3,!2'-,*m '+.*'!2'-,1m $-0m 1Yem #,-+#m#1mGO^G_[mJHjKLYm m 3+0ZmYZm+0!&#ZmY YZm1'ZmYYm^HFFM_Yme1#m-$m"+%#"mm,"m"m 13 1202#1m 7m 2&#m #00-0j.0-,#m m .-*7+#01#m m $0-+m $0'!,m 15',#m $#4#0m 4'031Yem '-!&#+'1207mJL^GH_[mINGJjHKYm m ,&,Zm YYZm #,Zm YYZm '-4,,-,'Zm YZm *##Zm Y Ym ^GOOJ_Ym e&#m ,#4#0m 0'.#m +322'-,m *-!)1m#2&7*#,#m.#0!#.2'-,m',m2-+2-Yem*,2m#**mL^J_[mKHGjIFYm m #m '%,-0Zm YZm 4-'1Zm YZm 3 #02Zm YZm #0"'#0Zm YZm '!-*1Zm Ym 7m !-*Ym ^HFFO_Ym e.2'+'8',%m m .-.3*2'-,1m $-0m 0#4#01#m %#,#2'!1m ',m #"'!%-m 203,!23*Yem *,2m '-2#!&,-*m mM^K_[mJIFjJGYm m #&+,Zm YZm *!)Zm YZm !)#0Zm YYm ^GOOL_Ym eGZm ,m #2&7*#,#m 0#1.-,1#m %#,#Zm '1m 0#/3'0#"m $-0m "'$$#0#,2'*m !#**m #*-,%2'-,m ',m 2&#m 0 '"-.1'1m &7.-!-27*Yem #**m NK^H_[mGNIjOJYm m #**'1Zm YYZm 11!&3Zm YYZm &'2&+Zm YYZm 00',%2-,Zm YYm ^HFFH_Ym e-11j-$j 131!#.2' '*'27m +32,21m -$m 0 '"-.1'1m 2&*',m 0#4#*m ,m #11#,2'*m 0-*#m $-0m #^'1-_Jm "30',%m.-274'031m',$#!2'-,Yem300m'-*mGH^GH_[mGFJLjKGYm m #-,0"ZmYZm*,2#ZmYZm'22+,,ZmYZm'%,#3*2ZmYZm-02',ZmYYm7m!-*Ym^HFFF_Ym e-+.*#6m$-0+2'-,m #25##,m.-274'031m%m,"m20,1*2'-,m#3)07-2'!m','2'2'-,m$!2-0m Jm!-00#*2#1m5'2&m4'031m',$#!2'4'27Yem m'0-*mMJ^GM_[mMMIFjMYm m #5'1ZmYZm- #021mYZm* #021m^HFFL_Ymem<*3*Yem"'!'-,#1m+#%Ym"0'"Ym m 'ZmYZm-,%ZmYZm#,2307ZmYZm20'%&2ZmYZm-,*"ZmYm7m!-*Ym^HFFG_Ymem$12m,#320-,m "#*#2'-,m+32%#,#1'1j 1#"m0#4#01#m%#,#2'!1m1712#+m$-0m.*,21Yem*,2m mHM^I_[mHIKjJHYm m 'ZmYZm&,%ZmYm^HFFH_Yme#4#01#m%#,#2'!1m 7m$12m,#320-,m+32%#,#1'1m',m&'%&#0m .*,21Yem3,!2m,2#%0m#,-+'!1mH^L_[mHKJjNYm HFFm #&#)!, 7O m m 'Zm YYZm 22&#51Zm YYZm 300Zm YZm 3028#*Zm YYm ^GOOL_Ym e*-,',%m ,"m !&0!2#0'82'-,m -$m m +'8#m !m #,!-"',%m .&72-#,#m "#12301#Zm ,m #,87+#m -$m 2&#m !0-2#,-'"m '-17,2&#2'!m.2&57Yem*,2m-*m'-*mIF^H_[mHLOjMOYm m ',"#,Zm YZm '15Zm YZm &+-4'28Zm YZm #!)#0Zm YZm '01!& #0%Zm Ym 7m !-*Ym ^GOOG_Ym e3,!2'-,*m!-+.*#+#,22'-,m',m1!&#0'!&'m!-*'m-$m"'$$#0#,2m.&72-#,#m"#12301#m%#,#1m ,"m,*71'1m-$m!!3+3*2#"m!0-2#,#1Yemm230$-01!&mmJL^GGjGH_[mGFJKjKGYm m A.#8j0Zm YYZm -&*#,)+.Zm YZm #'%#0Zm Ym ^HFFL_Ym e&#m .-12j%#,-+'!m #0jj 5&2m!-+#1m,#62]em#4m2',-+m'!0- '-*mJN^G_[mJJjKYm m A.#8j#8Zm YYZm*-01ZmYZm0!'Zm YYZm-8-ZmY Ym^HFGG_Ymem17+ '-1'1m*2#01m .&#,-*'!m!'"m!-,2#,2m',m2-+2-m0--21Yem*,2m'%,*m#&4mK^O_[mGGINjJFYm m 3ZmYZm02',j#0,,"#8ZmYYZm#02Zm YYZm*!3'2ZmYZm3*!-+ #ZmYYm^HFFI_Ym e'031j',"3!#"m%#,#m1'*#,!',%m',m.*,21Yem#2&-"1mIF^J_[mHOLjIFIYm m 3," #0%Zm YYZm &-#+)#0Zm YYZm "+1Zm YYZm &-02Zm YYZm -0%#Zm YYm 7m !-*Ym ^GOOG_Ym e'%&j$'"#*'27m +.*'$'!2'-,m 31',%m m 2&#0+-12 *#m m .-*7+#01#m '1-*2#"m $0-+m70-!-!!31m$30'-131Yem#,#mGFN^G_[mGjLYm m 3-Zm YZm ,%Zm YYZm 0'1!&Zm YZm -- #30Zm YZm ',%Zm YYm 7m !-*Ym ^HFFG_Ym e#*-,m !2#0'*m 02'$'!'*m !&0-+-1-+#m ^_m *' 007m !-,1203!2'-,m 31',%m '+.0-4#"m +#2&-"1m ,"m'"#,2'$'!2'-,m-$m!*-,#1m*',)#"m2-m2&#m*-!31m!-,$#00',%m0#1'12,!#m2-m+#*-,m310'3+m 5'*2m^-+jH_Yem#,-+#mJJ^H_[mGKJjLHYm m ,8--0ZmYZm&##+ZmYm^HFFI_Yme"'-1#,1'2'4'27m123"'#1m',m 1+2'm0'!#Yem)Ym Ym-2mIK^H_[mGOMjHFMYm m 02',ZmYZm0-"#!ZmYZm-3*#+ZmYZm( ZmYZm#0,,"#8ZmYm7m!-*Ym^HFFO_Ymem 20,1.-1-,j',"3!#"m #.'%#,#2'!m !&,%#m *#"1m 2-m 1#6m "#2#0+',2'-,m ',m +#*-,Yem 230#m JLG^MHLM_[mGGIKjNYm m 02',ZmYYZm-%",-4#ZmY YZm#11ZmYm^HFFI_Yme,"#012,"',%m2&#m$3,!2'-,1m-$m .*,2m"'1#1#m0#1'12,!#m.0-2#',1Yem,,3m#4m*,2m'-*mKJ[mHIjLGYm m 1!0#**j0#31ZmYZm,'80#1Zm YZm'*001j*1'Zm YZm-0j0!'ZmYZm*,!Zm Ym 7m!-*Ym^HFFO_Yme,m-*'%-j 1#"m+'!0-007m-$$#01m,-4#*m20,1!0'.2-+'!m..0-!&#1m$-0m2&#m ,*71'1m -$m .2&-%#,m 0#1'12,!#m ,"m $03'2m /3*'27m 20'21m ',m +#*-,m ^3!3+'1m +#*-m Y_Yem m#,-+'!1mGF[mJLMYm m 1&*ZmYYZm--,28Zm YZm)*0Zm Ym^GOOK_Yme#2#!2'-,m-$m+322'-,1m 7m!*#4%#m-$m m&#2#0-"3.*#6#1m5'2&m !2#0'-.&%#m0#1-*41#1Yem2m#,#2mO^H_[mGMMjNIYm m !**3+Zm YYZm -+'Zm YZm 0##,#Zm YYZm #,')-$$Zm Ym ^HFFFm _Ym e0%#2#"m 1!0##,',%m$-0m',"3!#"m+322'-,1Yem2m'-2#!&,-*mGN^J_[mJKKjMYm m !**3+Zm YYZm -+'Zm YZm 0##,#Zm YYZm #,')-$$Zm Ym ^HFFFm _Ym e0%#2',%m ',"3!#"m *-!*m *#1'-,1m m %#,-+#1m ^_m $-0m .*,2m $3,!2'-,*m %#,-+'!1Yem *,2m &71'-*mGHI^H_[mJIOjJHYm m !027Zm YYZm #22*#1Zm YYZm 383)'Zm YZm ,Zm YYZm 21&5Zm Ym 7m !-*Ym ^HFFK_Ym e2#"7j122#m20,1.-1-,m+32%#,#1'1m',m', 0#"m+'8#Yem*,2m mJJ^G_[mKHjLGYm m !-5#**Zm YYZm -$$#,"#,Zm Y Ym ^HFFI_Ym e*,2m "'1#1#m 0#1'12,!#m %#,#1[m 0#!#,2m ',1'%&21m,"m.-2#,2'*m..*'!2'-,1Yem0#,"1m'-2#!&,-*mHG^J_[mGMNjNIYm HFGm O #&#)!, 7m m !'**',Zm YYZm !,"*'-1Zm YYm ^GONI_Ym e#,#2'!m ,*71'1m -$m 2&#m "3.*'!2#"m +'2-!&-,"0'*m,"m!72-1-*'!m+*2#m"#&7"0-%#,1#m'1-87+#1m',m+'8#Yem1-87+#1m300m -.m'-*m#"m#1mN[mLMjOFYm m #',)#Zm YYZm &#007Zm YYZm #,Zm YZm -3,1*#7Zm YYZm --0,,##$Zm Ym ^GOON_Ym e0 '"-.1'1m2&*',[mm+-"#*m.*,2m$-0m%#,-+#m,*71'1Yem!'#,!#mHNH^KINO_[mLLHZmLMOj NHYm m m m #7#0Zm YYZm #*#3Zm YZm 0!'j1Zm YZm 4#7Zm Y Ym ^HFFN_Ym e-,1203!2'-,m -$m m $-1+'"m *' 007m -$m !3!3+ #0m ^3!3+'1m 12'431_m ,"m !-+.02'4#m ,*71#1m -$m 2&#m #Jm ,"m #^'1-_Jm 0#%'-,1m $0-+m !3!3+ #0m ,"m +#*-,m ^3!3+'1m +#*-_Yem -*m #,#2m #,-+'!1mHMO^K_[mJMIjNFYm m #7#01Zm YYZm '!)#0+,Zm YYZm '!&#*+-0#Zm YYZm '40+)0'1&,,Zm YZm - 0*ZmYYm7m!-*Ym^GOOO_Yme*,2m"'1#1#m0#1'12,!#m%#,#1m#,!-"#m+#+ #01m-$m,m,!'#,2m ,"m "'4#01#m .0-2#',m $+'*7m 5'2&',m 2&#m ,3!*#-2'"#j ',"',%m 13.#0$+'*7Yem *,2m m HF^I_[m IGMjIHYm m ',-'ZmYZm#20-88ZmYZmd,-$0'-ZmYZm'0-,ZmYZm-1!ZmYm7m!-*Ym^HFGF_Ymem,#5m +32,2m%#,#2'!m0#1-30!#m$-0m2-+2-m!0-.m'+.0-4#+#,2m 7mm2#!&,-*-%7Yem m #1m-2#1mI[mLOYm m -,$-02#ZmY YZm*'4#0ZmYZm-,8*-ZmY YZm*40#8Zm YYZm-*!#2j,(3,ZmYm7m!-*Ym ^HFFJ_Ym e"#,2'$'!2'-,m -$m /3,2'22'4#m 20'2m *-!'m ',4-*4#"m ',m $03'2m /3*'27m 20'21m ',m +#*-,m ^3!3+'1m+#*-mY_Yem&#-0m..*m#,#2mGFN^J_[mMKFjNYm m -,2#*-,#YZm YYm ^GOON_Ym e322'-,Zm 32%#,1Zm ,"m m #.'0Yem "'2-0'*[m 3+,m#,#2'1m"'2-0Ym,11m22#m,'4#01'27Ym,11Ym m --0#ZmYZm0# *-4Zm YZm72-,ZmYZ'-4,,-,'Zm Ym^HFFH_Yme1#m-$m%#,-+'!1m2--*1m 2-m'1-*2#m)#7m0'.#,',%m%#,#1m,"m,*71#m$03'2m+2302'-,m',m2-+2-Yem m6.m-2mKI^IMM_[m HFHIjIFYmm m -0#,-Zm YZm ,"-Zm YYZm -1j,2-1Zm YZm #0,,"#8j03('**-Zm YYZm -,$-02#Zm Y Ym7m!-*Ym^HFFN_Yme,"'"2#m%#,#1m,"m1m$-0m$03'2m0'.#,',%m,"m1-$2#,',%m',m+#*-,Yem &#-0m..*m#,#2mGGL^J_[mKNOjLFHYm m -0%,2#ZmYZm*'4'#0'ZmYYm^GOOI_Ymej.*'$'#"m+'!0-12#**'2#1m1mm+0)#01m ',m.*,2m%#,#2'!1mem*,2mm mI[mGMKjGNKYm m + 0Zm YZm #'2&Zm YZm !-302Zm YZm '2-Zm Ym ^GOOJ_Ym e1-*2'-,m -$m ,m ',2#0,*m "#*#2'-,m+32,2m-$m2&#m0 '"-.1'1m2&*',mIm%#,#Yem*,2m#**m&71'-*mIK^I_[mKFOjGIYm m '!'1#Zm YZm #0+,j#2,Zm YZm ,(3,Zm YZm 3 0,Zm YYZm 8'#0Zm Ym 7m !-*Ym ^HFFI_Ym e&#m #3)07-2'!m 20,1*2'-,m ','2'2'-,m $!2-0m Jm !-,20-*1m *#223!#m 131!#.2' '*'27m 2-m 2&#m-274'031m#223!#m+-1'!m4'031Yem*,2m&71'-*mGIH^I_[mGHMHjNHYm m '#2-Zm YZm -0*#1Zm YZm 0(#"Zm YZm *#.#2Zm YZm -,$-02Zm Ym 7m !-*Ym ^HFFL_Ym e,m #Jm **#*#m !-,$#01m 0#1'12,!#m 2-m ,m 3,!..#"m ,"m ,-,j.-*7"#,7*2#"m m 4'031m ',m +#*-,Yem*,2m mJN^I_[mJKHjLHYm m '#2-Zm YZm '0-,Zm YZm *+'1Zm YZm 0!-Zm YYZm -0'-,#1Zm Ym 7m !-*Ym ^HFFM_Ym e!-m $-0m 2&#m '"#,2'$'!2'-,m -$m **#*'!m 40',21m -$m +#*-,m #JZm m $!2-0m 2&2m !-,20-*1m4'031m131!#.2' '*'27Yemm*,2m'-*mM[mIJYm HFHm #&#)!, 7O m m '1&'7+Zm YZm 3'1Zm YZm -1#Zm YYZm 3 -Zm YZm #,,#22Zm YYm 7m !-*Ym ^HFFM_Ym e2&7*#,#m0#%3*2'-,m-$m$03'2m1-$2#,',%m,"m!#**m5**m"'111#+ *7m',m&0#,2'1m+#*-,Yem m 6.m-2mKN^L_[mGHNGjOFYm m -,)Zm YZm 3&1&'Zm YZm )"Zm YZm 3%50Zm YZm ',+'15Zm Ym ^HFFN_Ym e2&7*#,#m .0-"3!2'-,m ',m .*,21m "30',%m %#,#m 20,1$-0+2'-,m 13..0#11#1m 4'0m %#,#m #6.0#11'-,m',m%0- !2#0'3+m23+#$!'#,1Yem#5m&72-*-%'12mGMN[mLJMjLKLYm m 3,#8j*#,'31Zm YYZm ,2*'$$#Zm Y YZm 3 #0Zm Y YZm '0"'Zm YZm *##Zm Y Ym ^HFFL_Ym e0,1$-0+2'-,m -$m m +31)+#*-,m d*'dm &7 0'"m .0#,2*m *',#m ^3!3+'1m +#*-m Ym 40Ym 0#2'!3*231m#0Y_m5'2&m,m,2'1#,1#mm-6'"1#m%#,#Yem*,2m#**m#.mHK^I_[mGONjHFKYm m 3,#8j*#,'31ZmYYZm-+#8j'+ZmYZm!&-j*#(-ZmYZm03+#2ZmYZm#12#0ZmYm 7m !-*Ym ^HFFN_Ym e#*-,m $03'21[m %#,#2'!m "'4#01'27Zm .&71'-*-%7Zm ,"m '-2#!&,-*-%7m $#230#1Yem 0'2m#4m'-2#!&,-*mHN^G_[mGIjKKYm m *#7)-51)'Zm YYZm 0-,1-,m 3**',1Zm YYZm -"5',Zm YYZ#3,%Zm YYm ^GOON_Ym e322'-,m"#2#!2'-,m31',%mm,-4#*m.*,2m#,"-,3!*#1#Yem3!*#'!m!'"1m#1mHL^HF_[mJKOMj LFHYm m *'4#0ZmYZm0!'j1Zm YZm0"B1ZmYZm3#7-ZmYZm-.#8j#1#ZmYYm7m!-*Ym^HFFG_Ym e-,1203!2'-,m-$mm0#$#0#,!#m*',)%#m+.m$-0m+#*-,Yem#,-+#mJJ^K_[mNILjJKYm m ..#,&#'+#0Zm YYZm #47Zm YYZm ',&Zm YZm #*j"'Zm YZm .388-Zm YYm 7m !-*Ym ^GOOH_Ym e"'-,#!0-1'1m 1#!-,"07m 2-m ',2#012'2'*m 0!&72&#0.7[m !-00#*2'-,m -$m +%,#2'!m 0#1-,,!#m'+%',%m,"m&'12-.2&-*-%7Yem#30-130%#07mIG^H_[mIILjJIYm m 11-51)'ZmYZm!&,## #0%#0ZmYZm3!1j*#"-Zm YYZm02&+,,ZmYZm*0)ZmYYm7m !-*Ym^HFGF_Yme&#m02#m,"m+-*#!3*0m1.#!203+m-$m1.-,2,#-31m+322'-,1m',m0 '"-.1'1m 2&*',Yem!'#,!#mIHM^KOLG_[mOHjJYm m 0)#0Zm YYZm -*#+,Zm Y Ym ^GOOM_Ym e-*#!3*0m ',2'+!7m #25##,m .0-2#',1m 1.#!'$7',%m.*,2j.2&-%#,m0#!-%,'2'-,Yem0#,"1m'-!&#+m!'mHH^N_[mHOGjLYm m 3*',#ZmYZm#,')-$$ZmYm^HFFG_Yme0#"'!2',%m"#*#2#0'-31m+',-m!'"m13 12'232'-,1m -,m.0-2#',m$3,!2'-,Yem#,-+#m#1mGG^K_[mNLIjMJYm m 3*',#ZmYmZm#,')-$$ZmYm^HFFI_Yme[m.0#"'!2',%m+',-m!'"m!&,%#1m2&2m$$#!2m .0-2#',m$3,!2'-,Yem3!*#'!m!'"1m#1mIG^GI_Ym m 3/3#2Zm YZm 30%3#2Zm YZm %#,Zm Ym ^HFFJ_Ym .j 1#"m !*-,',%m -$m 2&#m 2m %#,#m $0-+m+#*-,m!-,$#00',%m0#1'12,!#m2-m -2&m.&'"m!-*-,'82'-,m,"m.&'"m20,1+'11'-,m-$m 1#4#0*m4'031#1Ym,[m# #"ZmYZm0'1ZmYm"'2-0'*Ym*!)m,'4#01'27Zm*-+-3!Zm8#!&m #.3 *'!Ym m #!)#0Zm YZm &+-4'28Zm YZm ',"#,Zm YZm ,"+,,Zm YZm '01!& #0%Zm Ym ^GOOH_Ym em 1',%*#m .-*7.#.2'"#m !2*78',%m 2&#m !-,4#01'-,m -$m .&72-#,#m 2-m 8#2j!0-2#,#m '1m 20,1!0'.2'-,**7m 0#%3*2#"m "30',%m 2-+2-m $03'2m 0'.#,',%Yem 0-!m 2*m !"m !'m m m m NO^GG_[mJOLHjLYm m #0',ZmYZmA+#8j '+<,#8ZmYZm%#,ZmYZm-%'+-,2ZmYZm#!&Zm YYm7m!-*Ym^HFFH_Ym e-*#!3*0m ,"m %#,#2'!m !&0!2#0'82'-,m -$m m ,-,j!*'+!2#0'!m .&#,-27.#m ',m +#*-,m 0#4#*1m25-m*-!'m!-,$#00',%m*2#0#"m#2&7*#,#m0#1.-,1#m',m$03'2Yem*,2m&71'-*mGHO^G_[mIFFj OYm HFIm O #&#)!, 7m m #007Zm YYZm ,%Zm YYZm #*&+Zm Y YZm 0",#0Zm YZm ')#Zm YYm 7m !-*Ym ^HFFI_Ym em m0#4#01#m%#,#2'!1m2--*m,"mm5# j!!#11' *#m!-**#!2'-,m-$m+32,21m-$m2&#m*#%3+#m -231m(.-,'!31Yem*,2m&71'-*mGIG[mNLLmjmNMGYm m '0-,Zm YZm '!-*'Zm YZm ',-'Zm YZm '#",-'0Zm YZm -0#22'Zm Ym 7m !-*Ym ^HFGF_Ym e,m ',"3!#"m +322'-,m ',m 2-+2-m #Jm *#"1m 2-m '++3,'27m 2-m 25-m .-274'031#1Yem -m ,#m K^L_[m#GGIGIYm m '202Zm YZm ,#*2Zm YZm ++#0Zm ^HFFF_Ym e-+#m !-++#,21m -,m ',$01.#!'$'!m !*11'$'!2'-,m-$m!3*2'401m-$m+#*-,Yem!2m-02Ym^_mKGF[mHOjIYm m -02,-7ZYZ' #0ZYZ-**-!)ZYZ0!&'Zm YZ#4Zm Ym ^HFGG_Ym e1#m -$m ,-,j ,-0+*'8#"Zm -,j+.*'$'#"m !m $-0m JKJj1#"m m #/3#,!',%m -$m *#1&7m #*-,m 03'2eYm*,2m#,Ym^J_[mILjJLYm m 0-44'"#,2'Zm YZm +.2-,Zm YYm ^GOOH_Ym e-30!#1m -$m 0#1'12,!#m 2-m 4'031#1m ',m 2&#m -274'0'"#Yem0!&m'0-*m3..*mK[mGNOjHGGYm m ',m Zm 3Zm YZm Zm YZm #,%Zm YZm #,%Zm YZm 7m !-*Ym ^HFFM_Ym e'103.2'-,m -$m .&72-#,#m "#12301#m %#,#m 0#13*21m ',m * ',-m ,"m "50$m .&#,-27.#1m ',m 0 '"-.1'1m 7m '+.'0',%m !&*-0-.&7**Zm !0-2#,-'"Zm ,"m %' #0#**',m '-17,2&#1'1Yem #**m #1#0!&Ym GM^K_[m JMGjNHYm m 3"0,ZmYZm-"0>%3#8ZmYYZmA.#8ZmYZm#0+B"#8ZmYZm3,#1j#1'ZmYm7m!-*Ym ^HFGG_Yme-3.*',%m4'031j',"3!#"m%#,#m1'*#,!',%m2-m#6-%#,-31m%0##,m$*3-0#1!#,!#m.0-2#',m #6.0#11'-,m .0-4'"#1m m &'%&*7m #$$'!'#,2m 1712#+m $-0m $3,!2'-,*m %#,-+'!1m ',m 0 '"-.1'1m ,"m!0-11m**m12%#1m-$m2-+2-m$03'2m"#4#*-.+#,2Yem*,2m&71'-*mGKL^I_[mGHMNjOGYm m <"#'ZmYYZm-,!8YZmm^GOOH_Yme*11'!*m+32%#,#1'1Yem#2&-"1m',m0 '"-.1'1m 0#1#0!&YmHI^N_mGIJYm m '!)ZmYZm3*2#0ZmYm^GOKL_Yme72-%#,#2'!1m-$m2&#m2-+2-Yem"4m#,#2m[mHLMj INHYm m '%-*ZmYZm,m#4#0#,Zm YZm ,11#,ZmYZm-,,#ZmYZm!&,#'"#01ZmYm7m!-*Ym^HFFO_Ym e'%&j2&0-3%&.32m"#2#!2'-,m-$m',"3!#"m+322'-,1m,"m,230*m40'2'-,m31',%m#7-',2m 2#!&,-*-%7Yem-m,#mJ^I_[m#JMLGYm m - %*'Zm YZm 0,2Zm Ym ^HFFL_Ym e0,1*2'-,m ','22'-,m $!2-01[m m 5#)m *',)m ',m .*,2mm4'031m',$#!2'-,Yemm',m*,2m!'#,!#mGG^G_Ym m -"0>%3#8Zm YYZm 0#'0#Zm YYZm +'**#0'Zm YZm - %*'Zm Ym ^GOON_Ym e&#m 0 '"-.1'1m 2&*',m !1m !-"',%m $-0m #Jm ,"m #^'1-_Jm 0#m ,-2m $3,!2'-,**7m #/3'4*#,2m $-0m 7#12m !-+.*#+#,22'-,m ,"m 0#m "'$$#0#,2'**7m #6.0#11#"m "30',%m .*,2m "#4#*-.+#,2Yem*,2m mGI^J_[mJLKjMIYm m -"0>%3#8j#0,9,"#8Zm YYZm -1*4#8Zm YZm #+.#0#Zm YYZm 30%-1Zm YZm 0,"Zm YYm7m!-*Ym^HFGH_Yme#*-,mm',2#0$#0#,!#m^'_m*',#1m1'*#,!#"m$-0m+j#Jm1&-5m 0-"m4'031m0#1'12,!#Yem-*m*,2m2&-*mGI^M_[mMKKjLIYm m -+#0Zm YZm &,Zm YZm -0",Zm YZm 20311Zm YZm -,1Zm Ym 7m !-*Ym ^HFFM_Ym e*,2m .2&-%#,m 0#!-%,'2'-,m +#"'2#"m 7m .0-+-2#0m !2'42'-,m -$m 2&#m .#..#0m 1Im 0#1'12,!#m %#,#Yem!'#,!#mIGN^KNKF_[mLJKjNYm HFJm #&#)!, 7O m m -1#m YYZm"$'#*"ZmYYm^GOON_Yme#+.-0*m1#/3#,!#m-$m!#**m5**m"'111#+ *7m ',m0.'"*7m0'.#,',%m+#*-,m$03'2ZYem*,2m&71'-*mGGM[mIJKjILGYm m -12Zm YZm ,"#0Zm Ym ^GOOI_Ym e0#"'!2'-,m -$m .0-2#',m 1#!-,"07m 1203!230#m 2m #22#0m 2&,mMFPm!!30!7Yem m-*m'-*mHIH^H_[mKNJjOOYm m 3$$#*ZmYZm3113*2ZmYYZm**-'6ZmYZm-307ZmYZm#,"&+,#ZmYm7m!-*Ym^HFFH_Ym em,230*m0#!#11'4#m0#1'12,!#m%#,#m%',12m.-22-m4'031mm',m.#..#0m!-00#1.-,"1m2-m2&#m #3)07-2'!m','2'2'-,m$!2-0mJm^#J_Yem*,2m mIH^L_[mGFLMjMKYm m 3$$#*Zm YZm 0,2Zm YZm **-'6Zm YZm #$# 40#Zm YZm -!&#Zm Ym 7m !-*Ym ^HFFJ_Ym e203!230*m ,*71'1m -$m 2&#m #3)07-2'!m ','2'2'-,m $!2-0m Jm %#,#m !-,20-**',%m .-274'031m 0#1'12,!#m',m.#..#0[m#6.*-'22'-,m-$mmm*' 007Yem#,#mIIN^H_[mHFOjHGLYm m 3$$#*ZmYZm**-'1Zm YYZm#1%#ZmYYZm0,2ZmYm^HFFK_Yme&#m0#!#11'4#m.-274'031m 0#1'12,!#m %#,#m .-2jGm '1m 2&#m 2-+2-m -02&-*-%3#m -$m 2&#m .#..#0m .40Hj#Jm %#,#Yem -*m #,#2m#,-+'!1mHMJ^J_[mIJLjKIYm m #22ZmYZm* ZmYZm*,!-ZmYZm-,2#+300-ZmYm^HFGG_Yme3,[mmm 0#1-30!#m$-0m%#,#m$3,!2'-,m,*71'1m',m13,$*-5#0Yem*,2m#2&-"1mM^G_[mHFYm m )+-2-Zm YZm ,Zm YYZm 1#Zm YZm &')8-,-Zm YZm 213,%Zm Ym 7m !-*Ym ^HFFI_Ym e'103.2'-,m -$m 2&#m 2Im %#,#m !31#1m &7.#01#,1'2'4'27m 2-m 3*204'-*#2m m *'%&2m ,"m %++j071m ',m 0 '"-.1'1[m '+.*'!2'-,m -$m 2&#m .0#1#,!#m -$m m 20,1*#1'-,m 17,2&#1'1m +#!&,'1+m',m.*,21Yem*,2m#**mGK^O_[mHFJHjKMYm m *"'<Zm YZm -1#Zm YZm '!#,2#Zm Ym ^HFFM_Ym e&#m *',)%#m #25##,m !#**m 5**m +#2 -*'1+m,"m$03'2m1-$2#,',%[m*--)',%m2-m2&#m$3230#Yem m!'m--"m%0'!mNM[mGJIKjGJJNYm m ,1#4#0',-Zm YZm -+Zm YZm #m '+-,#Zm YZm ',-Zm YZm #*'2-Zm Ym 7m !-*Ym ^HFFO_Ym e" [m m '-',$-0+2'!1m .*2$-0+m $-0m .*,2m 0#1'12,!#m %#,#m ,*71'1Yem 3!*#'!m !'"1m #1mIN^2 1#m'113#_[mNGJjHGYm m 1)'ZmYZm213+-2-ZmYZm,2-,'-ZmYYZm%+30ZmYm^HFFK_Yme0-+m+..',%m 2-m1#/3#,!',%Zm.-12j1#/3#,!',%m,"m #7-,"Yem*,2m#**m&71'-*mJL^G_[mIjGIYm m 2-j0m3+'ZmYjYYm^GOOO_Yme2&7*#,#m#!#.2-01m,"m#,#2'!m,%',##0',%m-$m 2&7*#,#m#,1'2'4'27mem*,2m'-2#!&,-*-%7mGL^K_[mIHGjIIJYm m !&**#0Zm YYZm *##!)#0Zm YYm ^GOOK_Ym e2&7*#,#j ',"',%m 1'2#1m %#,#02#"m ',m 7#12m #6.0#11',%m2&#m0 '"-.1'1mGm%#,#Yem!'#,!#mHMF^KHJI_[mGNFOjGGYm m !&,#'"#0Zm YYm ^HFFH_Ym e*,2m '++3,'27m ,"m $'*+m -'0[m 5&2m %3+1&-#m "#2#!2'4#1m!,m2#!&m31m -32m.*,2j.2&-%#,m',2#0!2'-,1Yem#**mGFO^K_[mKIMjJFYm m # 12',Zm YYZm #*$-0"Zm YZm ,Zm YZm #,,#0Zm Ym ^HFGF_Ym 3!3+ #0m ^3!3+'1m 12'431_m,"m+#*-,m^Ym+#*-_m&4#m,3+#0-31m5'*"m0#*2'4#1m',m1'm,"m3120*'Zm,"m 2&#m 1'12#0m 1.#!'#1m -$m +#*-,m '1m $0-+m 3120*'Ym 0-!##"',%1m -$m 2&#m 2'-,*m !"#+7m -$m !'#,!#1m-$m2&#m,'2#"m22#1m-$m+#0'!YmGFM[mGJHLOjMIYm m #$$#0,'!)Zm YYZm +,2Zm YYZm -3'#Zm YYZm !)#22Zm YYZm 3 0+,',Zm Ym ^HFFO_Ym e,4#12'%2'4#m +',',%m -$m 1#/3#,!#m "2m $-0m ,-4#*m #,87+#1[m m !1#m 123"7m 5'2&m ,'20'*1#1Yem m'-2#!&,-*mGJI^G_[mGMjHLYm m #%Zm YYm ^GONJ_Ym em 0#4'#5m -$m 2&#m %#,#2'!m #$$#!21m -$m #2&7*m +#2&,#13*$-,2#Yem 322m#1mGIJ^HjI_[mGGIjJHYm HFKm O #&#)!, 7m m #7+-30Zm YZm !*11-,Zm Ym ^^GOOI__Ym e#*-,1Ym ',m '-!&#+'1207m -$m 03'2m '.#,',%Yem"'2-0'*[m#7+-30mZm7*-0m Zm3!)#0mm^&.+,mXm**_Ym-,"0#1Ym.Ym HMIjHOFYm m &3,Zm YZm -721Zm YZm 23.0Zm YZm ^HFGH_Ym e#,-+#m ,%',##0',%m -$m !0-.1m 5'2&m "#1'%,#0m,3!*#1#1Ym&#m*,2m#,-+#YmKm^H_YmJHjKFYmm m &#**'#ZmYZm')*ZmYm^GOOI_Yme&#m!)m-$mm#1.'02-07m'1#m',m31)+#*-,m03'2m '.#,',%m -,m 2&#m *,2m &**#,%#1m 2&#m #$','2'-,m -$m *'+!2#0'!m #&4'-30Yem -30,*m -$m 1.#0'+#,2*m-2,7mJJ^N_[mGJFIjGJFLYm m &#,Zm YYZm &',Zm YYZm 00-7-j0!'Zm YZm !&-Zm YYZm 4#**#Zm YYm 7m !-*Ym ^HFFH_Ym e+Im '1m -,#m +#+ #0m -$m m *0%#m !-,12'232'4#*7m #6.0#11#"m $+'*7m -$m ,3!*#-2'"#m ',"',%m1'2#j*#3!',#j0'!&m0#.#2m#,!-"',%m%#,#1Yem-*m*,2m'!0- #m,2#0!2mGK^I_[mHKGj LGYm m m &')8-,-ZmYZm-)-2ZmYZm,)ZmYZm2, #ZmYZ,-ZmYm^GOON_Yme-*#!3*0m ,*71'1m -$m !0 -,m '-,j',"3!#"m +322'-,1m ',m 0 '"-.1'1m 2&*',Yem #,#1m #,#2m 712m MI^I_[mGMIjOYm m &')8-,-Zm YZm ,)Zm YZm 2, #Zm YZm ,-Zm Ym ^HFFG_Ym e#00,%#+#,21m -$m 2&#mm',m!0 -,m'-,j',"3!#"m+32,21m-$m0 '"-.1'1m2&*',Yem#,#2'!1mGKM^G_[mIMOj NMYm m m &')8-,-ZmYZm-)-2ZmYZm'2+30ZmYZm383)'ZmYZm2, #ZmYm7m!-*Ym^HFFI_Ym e322'-,m 02#m ,"m ,-4#*m 22m +32,21m -$m 0 '"-.1'1m 2&*',m ',"3!#"m 7m !0 -,m '-,1Yem #,#2'!1mGLI^J_[mGJJOjKKYm m &'0*#7ZmYYZm,*#7ZmYZm--"+,ZmYYm^GOOH_Yme$$#!21m-$m'-,'8',%m0"'2'-,m -,mm.*,2m%#,-+#[m,*71'1m-$m25-m0 '"-.1'1m20,1.0#,2m2#12m+322'-,1Yem*,2m#**m J^I_[mIIIjJMYm m )#*2-,Zm YYZm 3Zm YZm 0','41,Zm YZm ,1&0"2Zm YZm --0#Zm YYm 7m !-*Ym ^HFFL_Ym e'113#m"'$$#0#,2'*m#6.0#11'-,m-$m*7!-.#,#m #2j!7!*1#m%#,#m',m..7Yem#**m#1mGL^N_[m MIGjOYm m *"#Zm Y YZm 3#012#, #0%Zm YYZm -#$$*#0Zm YZm 2#',#Zm YYZ!!'-22'Zm Ym ^HFFK_Ym em 0#4#01#m%#,#2'!Zm,-,20,1%#,'!m..0-!&m2-m5&#2m!0-.m'+.0-4#+#,2m 7mYem2m '-2#!&,-*mHI^G_[mMKjNGYm m +'2&Zm YYZm 3Zm YYZm *40"-m 0#+#0Zm YYm ^HFGH_Ym e#2&-"-*-%'!*m 120#+*',',%m -$m m "'1!-4#07m ,"m %#,-27.',%m 4'm &'%&j0#1-*32'-,m +#*2',%m ,*71'1m ^_m',m,-,j+-"#*m1.#!'#1Yem0m#,-+'!1Ymm m - #0A,,m YZm3'0-%ZmYZm+.'#20-ZmYYm^HFFK_Yme2'*#,-eYm3 *'!"-m.-0m#*m ,12'232-m "#m 123"'-1m #%#2*#1Ym !3*2"m "#m '-/3>+'!m 7m 0+!'Ym ,'4#01'""m !'-,*m"#m3!3+9,Ym m -,%ZmYYZm,%ZmYYZm&#,ZmYYZm'+ZmYYZm'ZmYYm7m!-*Ym^GOOK_Ymem0#!#.2-0m )',1#j*')#m.0-2#',m#,!-"#"m 7m2&#m0'!#m"'1#1#m0#1'12,!#m%#,#ZmHGYem!'#,!#mHMF^KHJI_[m GNFJjLYm m .'#2&Zm YZm51-,ZmYm^HFFK_Ymem4#04'#5m-$m%#,#m1203!230#em-0+--)m -30,*[ &22.[ii555Y5-0+ --)Y-0%iYm HFLm #&#)!, 7O m m 0##*)1&+'Zm YZm 3.2Zm YZm -",.3Zm YZm &3&,Zm YYZm ,( +Zm Ym 7m !-*Ym ^HFFO_Ym e[m m 1'+.*'$'#"m .0-!#"30#m $-0m ,3!*#'!m !'"m #620!2'-,m $0-+m 007#"m 2'113#m $-0m m ,"m -2&#0m &'%&j2&0-3%&.32m 0#4#01#m %#,#2'!m ..*'!2'-,1Yem *,2m #2&-"1mL^G_[mIYm m 2# ',1Zm YYZm --"7Zm YYm ^GONO_Ym e-,!#0,',%m 2&#m &**+0)m -$m m "'1!0'+',2'-,Yem#&4m,*mGH^H_[mHFIjGGYm m 2#.,-4Zm YYZm !)#0Zm YYm ^HFFF_Ym e2&7*#,#m 1'%,*',%[m $0-+m +32,21m 2-m +-*#!3*#1Yem300m.',m*,2m'-*mI^K_[mIKIjLFYm m 2#.&#,1-,Zm YZm )#0Zm YZm '0',Zm YZm #0#8Zm YZm +-&Zm Ym 7m !-*Ym ^HFGF_Ym em 0'!&m m0#1-30!#m$-0m123"7',%m%#,#m$3,!2'-,m',m011'!m0.Yemm*,2m'-*mGF[mLHYm m 20!&,Zm YZm #"Zm YYm ^GOOO_Ym e3+,m -*#!3*0m #,#2'!1Yem "'2-0'*[m !'#,2'$'!m3 *'1&#01Ym6$-0"Ym m 20#'1',%#0Zm YZm 5#,Zm Ym ^GONK_Ym e#!&,'1+1m -$m 1.-,2,#-31m ,"m ',"3!#"m $0+#1&'$2m+322'-,m',m !2#0'-.&%#mJYem#,#2'!1mGFO^J_[mLIIjKOYm m 3 '7,ZmYYZm2#01ZmYYZm2'70ZmYYZm",,"ZmYYZm"""'ZmYm7m!-*Ym ^HFGH_Ym e#,-+#j5'"#m m .-*7+-0.&'1+1m ',m #*'2#m ',"'!m 0'!#m ', 0#"1m "'1!-4#0#"m 7m 5&-*#j%#,-+#m1#/3#,!',%Yem*,2m'-2#!&,-*m Ym m "+-0Zm YZm 28'0Zm YZm #'0Zm YZm )-4Zm YZm d0Zm Ym ^HFFM_Ym e,"3!#"m +32%#,#1'1m 2-m 3%+#,2m 2&#m ,230*m 40' '*'27m -$m +#*-,m ^3!3+'1m +#*-m Y_Yem 10#*m m *,2m!'mKK[mGKOjGLOYm m )3+'ZmYZm-7+ZmYZm3('50ZmYZm- 71&'ZmYm^HFGG_Yme"#,2'$'!2'-,m-$mm *0%#m "#*#2'-,m ',m 2&#m $'012m ',20-,m -$m 2&#m 0,jGm *-!31Zm 11-!'2#"m 5'2&m *-11m -$m 4#0,*'82'-,m 0#/3'0#+#,2m ',m 5'*"m 5&#2m .0-%#,'2-0m #%'*-.1m 231!&''m -11Yem #,#1m #,#2m712mNL^I_[mGNIjOKYm m *+#Zm YZm -4',Zm YZm ,%3',#2'Zm YYZm 3 #0-1Zm YZm 3,"/4'12Zm Ym 7m !-*Ym ^HFFN_Ym e-0#Zm m 0#1-30!#m $-0m 2&#m "'1!-4#07m -$m !&#+'!**7m ',"3!#"m +32,21m ',m 0*#7Yem*,2m'-2#!&,-*m mL^K_[mJMMjNKYm m ,)ZmYZm&')8-,-ZmYZm-)-2ZmYZm2, #ZmYZm,-ZmYm^GOOM_Yme$$#!21m-$m &#47m '-,1m -,m 2&#m %#0+',2'-,m ,"m 1304'4*m -$m 0 '"-.1'1m 2&*',Yem ,2m m "'2m '-*m MH^G_[mGHGjMYm m 7*-0Zm YYZm 0##,#Zm YYm ^HFFI_Ym e[m m 2--*m $-0m 2&#m ,*71'1m -$m ,3!*#-2'"#m.-*7+-0.&'1+1Yem3!*m!'"1m#1mIG[mINFNmjmINGGYm m &,&Zm YYZm &,Zm YYZm 1&')5Zm YZm 1&''Zm Ym ^HFGF_Ym em ,*71'1m $-0m $*-5#0',%m 2'+#m 31',%m !)!0-11m .-.3*2'-,m #25##,m 078m 12'4m '..-, 0#m ,"m Ym 03$'.-%-,Yem#,#1m#,#2m712mNK^J_[mHMIjOYm m '#+,ZmYYZm7*-0ZmYYZm'0"'Zm YYZ*##ZmY Ym^HFFF_Yme&#m2-+2-m#2&7*#,#m 0#!#.2-01m m ,"m #Jm 0#m ,#%2'4#m 0#%3*2-01m -$m #2&7*#,#m 0#1.-,1#m ,"m #6&' '2m $3,!2'-,*m!-+.#,12'-,m5'2&',mm+3*2'%#,#m$+'*7Yem0-!m2*m!"m!'mmmmOM^GF_[m KLLIjNYm m '**ZmY YZm-* #02ZmYZm-+.ZmYZm,,1ZmYYZm-"-+-ZmYYm7m!-*Ym^HFFI_Yme'%&j 2&0-3%&.32mm$-0m$3,!2'-,*m%#,-+'!1Yem#2&-"1m-*m'-*mHIL[mHFKjHFYm HFMm O #&#)!, 7m m '**Zm Y YZm #7,-*"1Zm YYZm #'*Zm YZm .0',%#0Zm YZm 302,#0Zm Ym 7m !-*Ym ^HFFJm _Ym e'1!-4#07m-$m',"3!#"m.-',2m+322'-,1m',m+'8#m%#,#1m 7mYemm*,2m'-*mJ[m GHYm m '**Zm Y YZm 302,#0Zm YZm -+'Zm YZm #,')-$$Zm Ym ^HFFJm _Ym e'1+2!&m !*#4%#m 7m 1',%*#j120,"m1.#!'$'!m,3!*#1#1Yem3!*m!'"1m#1mIH[mHLIHmjmHLJGYm m m '**ZmY YZm--.#0Zm YZm'ZmYYZm-*-5'2ZmYZm0##,#ZmYYm7m!-*Ym^HFFM_Yme'1!-4#07m -$m!&#+'!**7m',"3!#"m+322'-,1m',m0'!#m 7mYemm*,2m'-*mM[mGOYm m 0'/3#1Zm YZm 230 -'1Zm YZm **'1Zm YZm *+'1Zm YZm &34',Zm Ym 7m !-*Ym ^HFFM_Ym e&0!2#0'82'-,m-$m0 '"-.1'1m2&*',m+'1+2!&m1.#!'$'!m#,"-,3!*#1#1[m..*'!2'-,m 2-m+322'-,m"'1!-4#07m 7mm',m.#Yem*,2m mKG^L_[mGGGLjHKYm m 0-+1Zm YZm *#,Zm YYm ^HFGF_Ym e&#m 02#m ,"m 1.#!203+m -$m 1.-,2,#-31m +322'-,1m',mm.*,2mm4'031Yem#,#2'!1mGNK^I_[mONIjOYm m 03,'%#0Zm YZm '#2-Zm YZm -,89*#8j #1Zm YZm 0,"Zm Ym ^HFFN_Ym e#!&,'1+m -$m .*,2m #Jj+#"'2#"m 0#1'12,!#m %',12m m 0+-4'031m ^-+ 314'0'"#_[m !.j ',"#.#,"#,2m 20,1*2'-,m -$m m 4'0*m m !-,20-**#"m ',m !'1m 7m ,m ^_4'03*#,!#m "#2#0+',,2Yem*,2m mKL^K_[mMGLjHMYm m 1'Zm YZm -5#**Zm YZm '2!&#0Zm YZm '11'0',Zm YZm 21-,Zm Ym 7m !-*Ym ^HFGG_Ym e'1!-4#07m -$m 00#m +322'-,1m ',m .-.3*2'-,1[m m 7m 1#/3#,!',%Yem *,2m &71'-*m GKL^I_[mGHKMjLNYm m ."&77Zm YYZm &3Zm YYZm &2Zm YYm ^HFGF_Ym e0,1.-1-,m ',1#02'-,*m +32%#,#1'1m',m0'!#Yem#2&-"1m-*m'-*mLMN[mGJMjMMYm m ,m "#0m '#8#,Zm YYZm -,#1Zm YYm ^GOON_Ym e*,2m "'1#1#j0#1'12,!#m .0-2#',1m ,"m 2&#m%#,#j$-0j%#,#m!-,!#.2Yem0#,"1m'-!&#+m!'mHI^GH_[mJKJjLYm m ,m "#0m --0,Zm YYZm #m '2Zm Y YZm --12#,Zm YYm ^HFFH_Ym e*,!',%m 1#*#!2'-,m $4-01m%30"',%m0#1'12,!#m.0-2#',1Yem0#,"1m*,2m!'mM^H_[mLMjMGYm m ,m"#0m*,)Zm YYm^GOLK_Yme7,+'!1m-$m.'"#+'!1m-$m*,2m'1#1#[m-.3*2'-,m 30121m -$m $3,%'Zm !2#0'Zm -0m 4'031#1m ',m $'#*"m ,"m $-0#12m +)#m ,m ',2#0#12',%m "7,+'!*m 123"7Yem!'#,!#mGJM^ILKJ_[mGHFjJYm m ,m -'(#,Zm YZm ,m "#,m 30%Zm YYZm -0,#*'11#,Zm Y YZm ))#,Zm YYm ^HFFM_Ym e203!230#m ,"m $3,!2'-,m -$m 0#1'12,!#m .0-2#',1m ',m 1-*,!#-31m .*,21Yem ,,3m #4m &72-.2&-*mJK[mJIjMHYm m '%-30-36Zm YZm /3#2&Zm YYZm 213-)Zm YZm +'2&Zm YYZm #4'1Zm YYm 7m !-*Ym ^HFFH_Ym e2#m ,"m .22#0,m -$m +322'-,m 2m +'!0-12#**'2#m *-!'m ',m +'8#Yem -*m '-*m 4-*m GO^N_[mGHKGjLFYm m '**,3#4Zm YZm -,%j-,%Zm YZm --**'+1Zm YYm ^HFFH_Ym e0)#0m 11'12#"m 1#*#!2'-,m 5'2&m -.2'+'1#"m !-,20' 32'-,1m -$m 2&#m !,"'"2#1m 2-m 1#*#!2'-,Yem #,#2m #*m 4-*m IJ^L_[mLMOjMFIYm m -1ZmYZm-%#01ZmYZm*##)#0ZmYZm#'(,1ZmYZm,m"#m##ZmYm7m!-*Ym^GOOK_Yme[m m,#5m2#!&,'/3#m$-0mm$',%#0.0',2',%Yem3!*#'!m!'"1m#1mHI^HG_[mJJFMjGJYm HFNm #&#)!, 7O m m ,%Zm YYZm 3,Zm YYZm -Zm YYm ^HFFL_Ym e..*'!2'-,m -$m m ',m .*,2m '+.0-4#+#,2Yem'm&3,m3#m-mII^GG_[mOKMjLJYm m ,%Zm Ym^HFFG_Yme.2'+*m+0)#0j11'12#"m1#*#!2'-,m2-m',!0#1#m2&#m#$$#!2'4#m1'8#m -$m1+**m.-.3*2'-,1Yem#,#2'!1mGKM^H_[mNLMjMJYm m ,%Zm YZm -&*+'Zm YYZm 4'0!#4Zm YZm ,%Zm YZm ,$!-,Zm Ym 7m !-*Ym ^HFGI_Ym e'*#,!',%m-$m2&#m&-12m$!2-0m#^'1-_Jm%#,#m!-,$#01m.*3+m.-6m4'031m0#1'12,!#m',m.*3+Yem -m,#mN^G_[m#KFLHMYm m 02&+,,Zm YZm &#,Zm YZm 11-51)'Zm YZm #'%#*Zm YZm #04#Zm Ym ^HFFN_Ym e'%&*7m 1.#!'$'!m%#,#m1'*#,!',%m 7m02'$'!'*m+'1m',m0'!#Yem-m,#mI^I_[m#GNHOYm m #'*ZmYZm-,"#ZmYYm^HFFM_Yme#22',%m2-m2&#m.-',2mjm322'-,1m',m+'8#Yem0-.m !'mJM[mLFjLMYm m &'2)#0Zm YYm ^GOML_Ym e3!30 '21Zm -2,7Zm !3*2'42'-,m ,"m 32'*'82'-,Yem "'2-0'*[m,2#01!'#,!#m3 *'1&#01Ym3#4m-0)Ym m '#,&-*"1Zm YZm ,m #"#,Zm YZm -12#01Zm YZm 3""#Zm YZm *12#0)Zm YYm 7m !-*Ym ^HFFI_Yme$$'!'#,2m20%#2j1#*#!2#"m+32%#,#1'1m',m8# 0$'1&Yem#,-+#m#1mGI^GH_[mHMFFjMYm m '*)',1-,Zm YYZm,&,ZmYYZm#,ZmYYZm'-4,,-,'Zm YZm*##ZmY Ym^GOOK_Yme,m #2&7*#,#j',"3!' *#m !-+.-,#,2m -$m 1'%,*m 20,1"3!2'-,m #,!-"#"m 7m ,#4#0j0'.#Yem !'#,!#m HMF^KHJI_[mGNFMjOYm m '**'+1m^GOOF_Ymem.-*7+-0.&'1+m+.*'$'#"m 7m0 '2007m.0'+#01m0#m31#$3*m 1m%#,#2'!m+0)#01Yem3!*m!'"1m#1mGN[mLKIGjLKIKYm m ',)*#0ZmYZm!&5 #"'11#,ZmYZm!)1!&ZmYZm-)#*ZmYZm#'"#*ZmYm7m!-*Ym^HFFK_Ym e0%#2j1#*#!2#"m+32,2m1!0##,m 7mm',m0-1-.&'*Yem#,-+#m#1mGK[mMGNmjmMHIYm m '22+,,Zm YZm &2#*Zm YZm -02',Zm YYZm *' #02#Zm YYm ^GOOM_Ym e,2#0!2'-,m -$m 2&#m 4'0*m .0-2#',m %#,-+#m *',)#"m -$m 230,'.m +-1'!m .-274'031m 5'2&m 2&#m 20,1*2'-,*m #3)07-2'!m','2'2'-,m$!2-0m^'1-_mJm-$m0 '"-.1'1m2&*',m31',%m2&#m7#12m25-j&7 0'"m 1712#+Yem'0-*-%7mHIJ^G_[mNJjOHYm m -*$1 #0%Zm YYm ^HFGG_Ym e1',%m 2&#m m .m '#5#0m 2-m 0-51#m %#,-+'!m 1#/3#,!#m"2Yem300m0-2-!m3+m#,#2m&.2#0mGN[m,'2GNmKYm m 0'%&2Zm YYZ-721Zm YYm ^GOON_Ym e-2#,2'*m 0#20-4'031#1m ',m .*,21[m 2Gm '1m 0#*2#"m 2-m m %0-3.m -$m 0 '"-.1'1m 2&*',m 7Ii%7.17m 0#20-20,1.-1-,1m 2&2m #,!-"#m #,4#*-.#j*')#m.0-2#',1Yem#,#2'!1mGJO^H_[mMFIjGKYm m 3Zm YYZm 3Zm YZm #'Zm YZm 0-'",Zm YZm -0"#-1Zm Ym 7m !-*Ym ^HFFK_Ym e&#+'!*jm ,"m'00"'2'-,j',"3!#"m+32,21m-$m',"'!m0'!#mLJm$-0m$-050"m,"m0#4#01#m %#,#2'!1Yem *,2m-*m'-*mKO^G_[mNKjOMYm m ,%Zm YZm #,Zm YZm -"*'Zm YYZm *#7)-51)'Zm YYZm '**#0Zm YYm 7m !-*Ym ^HFFF_Ym e30'$'!2'-,Zm!*-,',%Zm,"m!&0!2#0'82'-,m-$m2&#mmm,3!*#1#Yem'-!&#+'1207mIO^GI_[m IKIIjJGYm m #,Zm YYZm ##Zm YZm ,)1*#7Zm YYZm ,&,Zm YYZm *##Zm Y Ym 7m !-*Ym ^GOOK_Ym e&#m 2-+2-m#4#0j0'.#m*-!31m0#%3*2#1m#2&7*#,#j',"3!' *#m%#,#m#6.0#11'-,m,"m'1m*',)#"m2-mm &-+-*-%m-$m2&#m0 '"-.1'1mGm%#,#Yem*,2m&71'-*mGFM^J_[mGIJIjKIYm HFOm O #&#)!, 7m m #3,%Zm YYZm 22,%"'Zm YZm *)#1*#7Zm YZm '!-*1Zm Ym ^HFFK_Ym e,87+2'!m +322'-,m"#2#!2'-,m2#!&,-*-%'#1Yem'-2#!&,'/3#1mIN^K_[mMJOjKNYm m m -3'*Zm YZm #+.#0Zm YYZm -22-,Zm YYm ^GOOK_Ym e!0##,',%m $-0m +322'-,1m 7m #,87+#m+'1+2!&m!*#4%#m5'2&mJm#,"-,3!*#1#mYem0-!m2*m!"m!'mmmmOH^G_[m NMjOGYm m 3ZmYYZm&',%ZmYYZm3ZmYYZm'ZmYYZm,%ZmYYm7m!-*Ym^HFGF_Yme#,#02'-,m -$m 20,1%#,'!m 52#0+#*-,m 0#1'12,2m 2-m 3!!&','m 7#**-5m +-1'!m 4'031m ,"m .7m 0',%1.-2m4'031m27.#mYem*,2m#**m#.mIF^I_[mIKOjMGYm m 0#+ ',1)'ZmYYZm&#-*-%'1ZmYm^GOOJ_Yme2&7*#,#m '-17,2&#1'1m,"m!2'-,[mm!1#m -$m!-,1#042'-,Yem*,2m-*m'-*mHL^K_[mGKMOjOMYm m &#,%ZmY YZm,-#0#,ZmYYZm-%#5-,',%ZmYYZm,m--,Zm Y YZm '!)#ZmYm^HFGF_Ym e'103.2'-,m -$m .*,2m !0-2#,-'"m '-17,2&#1'1m 2&0-3%&m 4'031j',"3!#"m %#,#m 1'*#,!',%m $$#!21m-4'.-1'2'-,m #&4'-30m-$m2&#m 322#0$*7m'#0'1m0.#Yem#5m&72-*mGNL^I_[mMIIjJKYm m &-,%Zm YZm ',Zm YZm 0'#01-,Zm Ym ^HFFN_Ym e-+2-m #2&7*#,#m 0#!#.2-0jm ',2#0!2'-,1[m 4'13*'82'-,m -$m ,#4#0j0'.#m ',2#0!2'-,1m 5'2&m +3*2'.*#m 1m 2m 2&#m #,"-.*1+'!m0#2'!3*3+Yem m6.m-2mKO^J_[mOLKjMHYm m m HGFm (2)O m TT T ,m#12#m,#6-m1#m.0#1#,2m#*m02>!3*-m.3 *'!"-m$032-Zm#,m%0,m.02#Zm"#*m20 (-m0#*'8"-m#,m#12m 2#1'1m"-!2-0*Ym#m',!*37#,m2+ '<,m"-1m02>!3*-1m/3#m,-m#129,m0#*!'-,"-1m!-,m*m2#+92'!m"#m*m 2#1'1Zm#,m*-1m/3#m1#m!-* -0Am.0*#*+#,2#m*m"#100-**-m"#m*m.- *!'A,m"#mm"#m+#*A,Ymm m T T T HGGm O (2)m T González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 RESEARCH ARTICLE Open Access Towards a TILLING platform for functional genomics in Piel de Sapo melons Mireia González1, Meihong Xu1,5, Cristina Esteras2, Cristina Roig2, Antonio J Monforte1,3, Christelle Troadec4, Marta Pujol1, Fernando Nuez2, Abdelhafid Bendahmane4, Jordi Garcia-Mas1 and Belén Picó2* Abstract Background: The availability of genetic and genomic resources for melon has increased significantly, but functional genomics resources are still limited for this crop. TILLING is a powerful reverse genetics approach that can be utilized to generate novel mutations in candidate genes. A TILLING resource is available for cantalupensis melons, but not for inodorus melons, the other main commercial group. Results: A new ethyl methanesulfonate-mutagenized (EMS) melon population was generated for the first time in an andromonoecious non-climacteric inodorus Piel de Sapo genetic background. Diverse mutant phenotypes in seedlings, vines and fruits were observed, some of which were of possible commercial interest. The population was first screened for mutations in three target genes involved in disease resistance and fruit quality (Cm-PDS, Cm-eIF4E and Cm-eIFI(iso)4E). The same genes were also tilled in the available monoecious and climacteric cantalupensis EMS melon population. The overall mutation density in this first Piel de Sapo TILLING platform was estimated to be 1 mutation/1.5 Mb by screening four additional genes (Cm-ACO1, Cm-NOR, Cm-DET1 and Cm-DHS). Thirty-three point mutations were found for the seven gene targets, six of which were predicted to have an impact on the function of the protein. The genotype/phenotype correlation was demonstrated for a loss-of-function mutation in the Phytoene desaturase gene, which is involved in carotenoid biosynthesis. Conclusions: The TILLING approach was successful at providing new mutations in the genetic background of Piel de Sapo in most of the analyzed genes, even in genes for which natural variation is extremely low. This new resource will facilitate reverse genetics studies in non-climacteric melons, contributing materially to future genomic and breeding studies. Keywords: Cucumis melo, inodorus, TILLING, mutant, disease resistance, fruit quality Background Melon (Cucumis melo L.) is an important vegetable crop. Genetic and genomic information for this crop is increasing significantly due to several national and international projects [1]. A broad range of genomic tools are available today [2-7]. An effort is also in progress, through a Spanish initiative, to obtain the whole genome sequence of this crop [8]. These tools are generating a lot of information about genes involved in various biological processes, such as plant resistance and fruit quality [9,10]. However, the tools necessary for reverse genetic * Correspondence: [email protected] 2 Institute for the Conservation and Breeding of Agricultural Biodiversity (COMAV-UPV), Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain Full list of author information is available at the end of the article studies to conduct the functional validation of candidate genes in melons are still limited. The TILLING (Targeting Induced Local Lesions in Genomes) method may represent an effective means of addressing limitations in melon research [11]. The application of TILLING has proved to be useful in identifying novel alleles in genes controlling traits of agronomic interest in legumes [12-15], cereals [16-23], solanaceous crops [24-26] and Brassica spp [27,28]. C. melo is a highly variable species divided into two subspecies, melo and agrestis. Most of the commercial cultivars belong to the inodorus and cantalupensis groups of the subspecies melo [29]. Cultivars of these two commercial groups are quite different in plant, flowering and fruit traits. Cantalupensis cultivars are © 2011 Picó et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. T HGHm (2)O m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 early flowering, frequently monoecious, and produce climacteric fruits (aromatic, medium sugar, soft fleshed and with a short shelf life), whereas inodorus are late flowering, mostly andromonoecious, and non-climacteric, producing non-aromatic, high sugar, firm-fleshed fruits with a long shelf life, and which are preferred in certain markets. These differences make breeding strategies and objectives quite different for the two groups of melons. A melon TILLING platform generated from a monoecious climacteric cantalupensis genotype has recently become available [30], and has proven to be useful for improving the shelf life of climacteric melons. A TILLING platform generated in an inodorus background might represent a useful resource for functional studies and for breeding non-climacteric melons. In this paper, we present the development of an EMSmutagenized population from an andromonoecious nonclimacteric inodorus melon type (Cucumis melo L. subspecies melo cv Piel de Sapo). In total, 2,368 M2 families were obtained. A diversity of interesting mutant phenotypes were observed in the field. In addition, several mutant families have been identified in several genes that were selected based on their potential contribution to fruit quality and disease resistance. Methods EMS mutagenesis of melon seeds The double haploid line, M62-113 (from Semillas Fito S.A.), belonging to the Piel de Sapo commercial type (Cucumis melo subsp melo var inodorus), was used as the starting cultivar. This is the parent of the melon genetic map and is one of the parents of the DHL line selected for the sequencing of the melon genome. Different batches of a total of ~12,000 M62-113 seeds were treated with the alkylant mutagen ethyl methanesulfonate (EMS). Different EMS concentrations were tested, and 1% was finally selected and tested on a larger batch of seeds. Seeds were first hydrated with tap water (16h), and were then soaked in tap water containing EMS concentrations (18 h). The treated seeds were thoroughly rinsed in tap water twice for 4 hours. After washing, seeds were placed on trays over wet paper, and were kept in a germination chamber overnight. ~5,000 mutant plants of this first (M1) generation were transplanted at the greenhouse. Plants were grown in two localities, in Barcelona (by Semillas Fito S.A. and IRTA) and in Valencia (by COMAV-UPV). Each M1 plant was selfed (1 fruit per plant) giving rise to the M2 seed. TILLING procedure Twenty seeds were sown per M2 family, and the germination percentage was scored. Finally, a total of 2,368 Page 2 of 11 mutagenized M2 families, which produced at least 10 viable seedlings in at least two plantings, were sampled for DNA extraction. 1-cm discs of tissue from 10 individual plants per M2 were pooled, and total DNA was extracted, quantified, diluted and organized into twentyfive 96-well plates. Using equivalent amounts of DNA from individual M2 families, the samples were pooled four-fold and organized into a 96-well format. Seeds of all pooled M2 populations are maintained at the Genebank of the COMAV-UPV, coded as F (S. Fito), I (IRTA) or C (COMAV-UPV) plus the corresponding number. Primer sets were designed from 3 genes that were selected based on their potential contribution to fruit quality and disease resistance: Cm-eIF4E (translation initiation factor 4E) and Cm-eIF(iso)4E (translation initiation factor E, Isoform) which are involved in resistance to viruses [31], and Cm-PDS (Phytoene Desaturase), which is involved in carotenoid synthesis [32]. The CODDLe program (Codons Optimized to Deliver Deleterious Lesions) [33] was used to select the regions most likely to harbor deleterious changes induced by EMS (Table 1). These 3 genes were tilled in the Piel de Sapo population as well as in a set of 2,483 available lines of the cantalupensis TILLING population reported in [30]. Four additional genes involved in fruit ripening were tilled in the Piel de Sapo population: Cm-ACO1 (ACC oxidase 1), involved in the conversion of ACC into ethylene [34]; Cm-NOR (non-ripening), a transcription factor related to ethylene-sensitive/insensitive phenotypes [35]; Cm-DET1 (de-tiolated-1), a negative regulator of light-mediated responses that affects carotenoid and flavonoid pathways in tomato and other crops [36,37]; and Cm-DHS (Deoxyhypusine Synthase), mutations of which delay fruit softening in tomato [38]. Primer sets used for these additional genes are the same as those used in [30]. The amplicons analyzed for each gene are indicated in Figures 1 and 2. Nested PCR was used to improve the specificity of amplification. The PCR reactions were performed in a 25 μl volume consisting of dH 2O, 1× PCR buffer (Promega Corp, Madison, WI), 2.5 mM MgCl 2 , 0.2 mM dNTPs, 1 U Taq polymerase, 0.4 mM forward and reverse primers, unlabeled in the first reaction, and 700 nm and 800 nm 5’ labeled (MWG Biotech AG, Germany) in the second reaction, and 10 ng DNA. The thermocycling conditions were 95°C for two minutes for initial denaturing, followed by 35 cycles of 95°C for 20 seconds, 63-69°C (specific for each primer pair) for one minute, 72°C from 30 seconds to one minute and one cycle of 72°C for five minutes. PCR products (~0.2 μl) were separated in 1% agarose gels. The PCR products were heated and cooled in a thermocycler (a gradient starting at 94°C and decreasing 0.1°C per second T HGIm O (2)m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 Page 3 of 11 Table 1 Primer pairs used to amplify the 3 target genes tilled in both EMS-mutant populations Gene Forward (*LabelledIRD700) Reverse (*LabelledIRD800) Cm-eIF4E 1st amplicon GACTCAAACGCCTAACAGAAAATC CTATCTCACCAAGTTTCCTAAATT *GAGGGCGGTGCCATTCTTCTTCGG *TCCCTAAATCGAACCAAGAAACGCC Cm-eIF4E 2nd amplicon TTGTTTCGTGTTGACATGTCCATC AGCATGCATTTCACCTCATTGGCT *TGCTTGGCTGTTAATTTATCTCTGC *GTCAAGTACAGAACAAGAATCTGAG Cm-eIF(iso)4E Cm-PDS GATCGATAATTTCCCTTTTC TGACAGGCTTAAGCACTATG *ACCCCAATTCATTCTAGGG *TGTGCAAGCGCAACAAGGTAC CAATGGGATGCTTAGATCAAC TCCTTCCAAAATTACCCTAG *GGATTTCTCGGAGTGACTCGG *GCTCTCGAGCAACTAGCACT Nested PCR was used in all cases with labeled primers in the second PCR. to 4°C) to form the heteroduplexes. Once the heteroduplexes were formed, the products were treated with Endo I. Digestions were performed in 30μl of final volume with dH2O, 3μl digestion buffer, 150 ng of PCR product and 3μl of EndoI (diluted 1/5000). The products were incubated at 45°C for 20 minutes to digest mismatches in the heteroduplex. Digestion was stopped by adding 5μl of 0.15 M EDTA and placing the reaction on ice. After the digestion was completed, the products were filtered through a Millipore MultiScreen filter plate that was packed with hydrated Sephadex G-50 medium beads (Amersham Biosciences). Samples were concentrated in the Speed Vac at 65°C for 45 minutes. Loading dye was added and the PCR products were denatured and loaded onto a polyacrylamide gel attached to a LI-COR 4300 DNA Analyzer (LICOR, Lincoln, NE) for separation. A total of 903 pools were assayed (592 four-fold pools of the Piel the Sapo population and 311 eight-fold pools of the cantalupensis population). Once a mutation was revealed in a pool, the corresponding families were 1169 500 1719 Cm-eIF4E 154 299 154 166 1 2 5 6 3 8 9 7 78 126 66 51 4 12 10 11 13 14 15 16 17 18 Cm-eIF(iso)4E 19 1188 Cm-PDS 1125 169 290 46 1476 45 754 188 116 161 20 22 58 21 23 24 25 Figure 1 Gene structure of the target genes screened in both populations,inodorus and cantalupensis, (eIF4E, eIF(iso)4E and PDS). Boxes represent exons and lines introns. White and black boxes indicate 3’UTR and 5’UTR regions. Amplicons analyzed by TILLING are indicated. Black and white triangles indicate mutations found in the inodorus Piel de Sapo and cantalupensis Charentais populations, respectively. Numbers correspond to the mutations described in table 3. HGJm (2)O m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 Page 4 of 11 933 933 107 103 150 Cm-ACO1 125 334 227 291 1272 89 Cm-NOR 184 26 182 314 564 1185 Cm-DET1 72 83 431 776 102 288 933 27 166 123 69 1232 182 28 29 198 136 57 81 30 578 Cm- DHS 624 84 166 93 96 31 754 168 803 106 219 32 87 33 Figure 2 Gene structure of the target genes screened in the inodorus population (ACO-1, NOR, DET-1 and DHS). Boxes represent exons and lines introns. White and black boxes indicate 3’UTR and 5’UTR regions. Amplicons analyzed by TILLING are indicated. Black triangles indicate mutations found in the Piel de Sapo population. Numbers correspond to the mutations described in table 3. analyzed individually to select the mutant M2 family. Mutation was confirmed by sequencing in the pooled DNA, in the individual M2 families and in several individual plants used in the segregation studies. The effect of the mutations was analyzed with SIFT (Sorting Intolerant from Tolerant, http://blocks.fhcrc.org/sift/SIFT.html) [39], which predicts whether an amino acid substitution affects protein function. Scores below 0.05 are predicted to affect protein function. Phenotyping of M2 and M3 individuals Seedling phenotypes were systematically evaluated in the M2 generation. Additionally, in order to increase the number of seeds in our mutagenized population, we obtained the M3 generation. M2 populations that are being reproduced are also being inspected for phenotypes that are distinct from the wild type in plant, flowering and fruit traits. To date, about 800 M2 plants have been reproduced by S. Fito. M3 plants are also being analyzed for ethylene-response mutants by growing seedlings in darkness with and without an air flux containing 10 microL L-1 ethylene, and analyzing the “triple response”. Results Generation of an EMS mutant population in the Piel de Sapo background We selected 0.5%, 1 and 1.5% for generating a pilot population of ~600 lines, and studied the effect of EMS dosage on M2 seed viability and seedling vigor. Increased EMS concentration led to an increased percentage of M2 fruits in which seeds were non-viable or in which the number of viable seeds was too low to perform TILLING analysis (13.24%, 27.75% and 31.38%, respectively). Only a slight reduction in the average germination rate was observed in M2 families obtained from 0.5% M1 (93.51%), whereas higher reductions were obtained in 1% and 1.5% (82.73 and 75.94%, respectively). In addition, seedling growth was more restricted at the 1.5% concentrations. In contrast, the progeny from the 1%-treated M1 were robust. Based on these results, 1% EMS was used in the end to complete the mutagenized melon population. This EMS dose produces an acceptable level of M1 seed survival, fertility in M1 plants to set viable M2 seeds, and vigor in M2 seedlings. From a total of 3,140 M1 fruits finally HGKm O (2)m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 Page 5 of 11 obtained, 2,368 M2 families were sampled for DNA and used for TILLING purposes. Phenotyping of the mutagenized population Ten plants per M2 line were scored for seedling phenotypes. A large number of the mutations affected cotyledons, with 5% of the M2 families showing variation in their number position and shape. About 4.3% of the M2 families segregated for “dwarf” or “semidwarf” plants. Albinism and chlorophyll deficiency occurred in 2.1% of the M2 families. Over 2% of the families showed alterations in leaves and shoot morphology. Gravitropic mutants and necrosis also appeared, but were less frequent. Figure 3 shows several seedling phenotypes. M3 families were characterized for plant flowering and fruit traits. Fruit traits of interest for melon breeding were identified: longer and rounder fruits than the standard Piel de Sapo fruits, with a lighter rind color, without the typical rind spots, and with different degrees of netting. Some lines have a subtle aroma and showed a color change and the formation of an abscission layer near maturity, a traits that are more similar to climacteric cantalupensis types than to the standard non-climacteric inodorus Piel de Sapo. Differences in the dark-grown seedlings’ response to ethylene were also observed. Wild type M62-113 showed the typical triple response: exaggeration of the apical hook, together with the inhibition of hypocotyl and root growth as well as the radial swelling of the shoot [40], whereas some M3 families showed responses of varying intensities (Figure 3). Identification of mutations in target genes by TILLING The TILLING approach allowed us to identify nucleotide changes in two of the three gene targets first screened in the Piel de Sapo population (Table 2). EMSinduced changes were mostly G:C to A:T transitions (67%) (Table 3), as was expected due to the frequent alkylation of guanine residues by EMS, thus forcing mispairing with T [41]. Four mutations were exonic, most of which were determined to be missense mutations, only one being silent. A graph of the target genes marking the location of the induced polymorphisms is shown in Figures 1 and 2. b Wild type Wild type c +Ethylene +Air +Ethylene +Air +Ethylene +Air +Ethylene +Air Wild type Figure 3 Images of selected mutant phenotypes observed in the melon TILLING population. a) Mutant seedlings found in M2. From left to right and from top to bottom, variations in cotyledons number and position, alterations in leaf and shoot morphology, albinism and chlorosis, including virus-like symptoms, dwarfing and altered gravitropism compared with seedling wild type. b) First row: Mutations found in adult M3 plants, chlorosis, dwarfing and leaf and flower deformation. Second row: alterations in fruits in comparison with wild type, deformation, chlorosis, rough surface, and pear-shape. Third row: fruit phenotypes of interest for melon breeding, variation in shape, longer and rounder melons, and melons with a subtle aroma and formation of abscission layer with or without color change. c) Variation in triple response: M2 families showing a more intense response to ethylene than wild type and others segregating for the response. HGLm (2)O m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 Page 6 of 11 Table 2 Comparison of the mutations found by TILLING in the gene targets screened in the two EMSmutagenized melon populations, Piel de Sapo (PS) and Charentais (CH) PS Population Gene CH population Exon/Intron-UTR Cm-eIF4E 3/1 CmeIF(iso)4E 0/0 5/9 1/0 Cm-PDS 1/1 1/3 TOTAL 4/2 7/12 Four new alleles were reported for Cm-eIF4E, defined by 4 mutations. Two (in exons 1 and 2) were predicted to affect protein function according to SIFT (p<0.05). The segregation of the missense mutations was analyzed in each mutant M2 family (Table 3) and homozygous individuals for each mutation are being produced for phenotypic analysis. Two new alleles were reported for Cm-PDS. Mutations were detected in the first intron and in the second exon of the amplicon (Figure 1). The exonic mutation was predicted to affect protein function. The genotype/phenotype segregation was verified for the Cm-PDS mutations in 15 plants of each M2. The intronic mutation found in M2 family F1151 (mutation 20 in Figure 1) presented a Mendelian segregation of 4 wild type/7 heterozygous/4 homozygous mutant (fitting to a 1:2:1 ratio) (Table 3). No associated phenotype was observed, which agrees with the position of the mutation in an intronic region. The M2 family C384 carried a missense mutation in exon 2 (mutation 21 in Figure 1). The segregation of M2 was 9 heterozygous/6 wild type. In this family, we observed that some plants showed delayed growth and even death at the cotyledon stage, and therefore could not be sampled. M3 seeds from a heterozygous M2 plant were used to repeat segregation analysis. Fourteen plants germinated out of the 20 seeds sown. Again, plants with delayed growth were observed, but we also found a seedling with albino cotyledons and hypocotyl (Figure 4). This seedling was carefully grown until tissue could be sampled for DNA extraction. The albino was the only plant homozygous for the mutant allele; the remaining M3 plants were wild type or heterozygous. This mutant line showed a similar albino phenotype comparable to the previously reported phenotypes for PDS disruption [32]. To further evaluate the mutation rate of the Piel de Sapo population, we extended the TILLING screen to 4 additional genes involved in fruit quality. Mutations were found for all genes, except for Cm-NOR, with Cm-DET1 being the most mutated gene. Six mutations were exonic, most determined to be missense, only one silent, but all were predicted to be tolerated (Figure 2, Table 3). Mutation efficiency We used these results to calculate the mutation rate of the population. A total of 14 point mutations were detected out of the total 11,534 bp analyzed. Previous studies reported the difficulty in tracking mutations on the ends of the fragments (~100 bp) [42]. Therefore, 200 bp was subtracted off each amplicon, and we considered the length screened in this study to be 9,134 bp. The overall mutation density was then calculated by dividing the total base pairs screened, which includes the sum of the total length of the 12 amplicon sizes × the total number of individuals screened, by the total number of mutations revealed by TILLING ((9,134 × 2,368)/14 = 1,544,950). It was calculated to be ~1/1.5 Mb. The mutation frequency as determined by TILLING is coherent with the moderate level of phenotypic mutants found in our population. In order to compare the inodorus and the cantalupensis populations, the same genes were screened in a set of 2,483 lines of the Charentais population [30]. The number of mutations was higher, and new alleles were found for the three genes (Table 2 Figure 1). The spectrum of observed changes was similar to that found in the Piel de Sapo population (Table 3). Only one mutation was found for Cm-eiF(iso)4E. Cm-eIF4E was also the most mutated gene with 14 mutations: seven intronic, two in the 3’UTR, and five exonic. Of the exonic mutations, two, located in exons 1 and 2, were not tolerated (p<0.05). One intronic mutation was located in the first nucleotide of intron 3, and may affect a splicing site. TILLING analysis also revealed four mutations in Cm-PDS, one of which was not tolerated. The 19 point mutations discovered in the 3,871 bp analyzed in the Charentais population make a mutation rate of ~1/401 Kb ((3,071 × 2,483)/ 19 = 401,331). This is about 3 times higher than that found in the Piel de Sapo population. This high mutation rate in the cantalupensis population has also been observed by screening additional genes in the final version of the population, which consists of 4,023 lines [30]. Discussion The TILLING platform reported here is the first ever developed in an andromonoecious non-climacteric inodorus melon genetic background. The mutation rate in the Piel de Sapo population was moderate. It is less mutated than the cantalupensis population that was developed using a different genotype and a different protocol for treating the seeds, which resulted in increased seed viability at higher EMS doses (1 to 3%). Our attempt was the first with Piel de Sapo melons, and results suggest that our EMS treatment causes a high level of seed lethality. Regarding the protocol, Charentais seeds were not hydrated before being treated. Seed hydration has been reported to activate cellular division and induce the HGMm O (2)m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 Page 7 of 11 Table 3 Details of the mutations found by TILLING in the gene targets screened in the two EMS-mutagenized melon populations, Piel de Sapo (PS) and Charentais (CH) Gene/ population Amplicon size (bp) Identified mutants N° Exon/ 1 Intron Position AA change M2 Family M2 segregation (WT/ H/M)2 Cm-eIF4E/PS 500 1 1 A 74 G R 25 K F2036 9/7/8 0.00 1169 3 5/3/0 0.00 Cm-eIF4E/CH 500 1169 3 11 Exon 1 SIFT score 2 Exon 2 G 385 A E 129 K F57 3 Exon 2 G 465 A T 155 T F1880 4 Intron 2 G/C 5 Exon 1 G 289 A E 97 K 53 6 Exon 1 C 294 T F 98 F 2532 7 Intron 1 G/A 8 Exon 2 C 401 T A 134 V 1229 0.10 9 Exon 2 G 407 A G 136 E 444 0.00 F959 0.02 1420 10 Intron 2 C/A 11 Intron 2 C/T 1287 12 Intron 3 G/A first nt of intron 13 Intron 3 C/T 14 Intron 3 C/T 15 Exon 4 G 616 A 16 Intron 4 C/T 2035 17 3’UTR T/C 1368 18 3’UTR G/A 2163 1115 splicing 1667 2646 1233 E 206 K 2060 0.09 222 TGA CmeIF(iso)4E/ PS 1014 0 - CmeIF(iso)4E/ CH 1014 1 19 Exon 1 Cm-PDS/PS 1188 2 Cm-PDS/CH 1188 Cm-ACO1/PS 933 Cm-NOR/PS Cm-DET1/PS 1185 776 Cm-DHS/PS 4 G 128 A R 43 K M1587 1.00 20 Intron 1 C/T F1151 4/7/4 21 Exon 2 C 560 T S 227 F C384 6/9/0 22 Exon 1 C 395 T S 172 F 1182 23 Intron 1 C/T 2495 24 Intron 1 T/C 1460 25 Intron 1 C/T 1226 0 - 933 1 26 Exon 4 C 728 T 1272 0 1 27 Exon 2 T 402 A L 135 L I76 2 28 Exon 4 G 760 A V 255 I 29 Exon 4 C 848 T S 284 L 30 Intron 6 G 2981 A T 243 I C142 0.00 0.01 10/6/3 1.00 F201 2/11/2 0.37 F1876 2/4/3 0.25 1232 2 F1248 31 Intron 7 C 3211 T 578 1 32 Exon 1 G 184 A V 62 I F 1728 754 1 33 Exon 3 G 610 A V 204 I C348 C487 13/20/0 0.58 2/6/0 0.27 1 Number of mutations corresponds to those represented in Figures 1 and 2 For some mutations, it was difficult to obtain homozygous MM plants as seedlings showed altered development. 2 repair of DNA damage [43]. Differences in seed structure between genotypes, as well as an increase in the efficiency and accuracy of the repair of the induced lesions may explain the differences between populations. Perhaps, HGNm using a higher EMS dosage and/or an extended length of mutagen application, combined with a more intense wash length, and a more accurate seedling nursery would have increased mutation efficiency. Other authors that (2)O m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 Page 8 of 11 M/M WT/WT WT/M Figure 4 Verification of genotype/phenotype relationship in the Cm-PDS gene. Chromatograms of wild type (WT), homozygous mutants (M) and heterozygous are shown for the C 560 T transition altering codon 227 S (serine) to F (phenylalanine) and predicted to affect the protein function. Segregation of the mutation was confirmed in M3 seeds from a heterozygous M2 plant. The albino was the only plant homozygous for the mutant allele; the remaining M3 plants were wild type or heterozygous. also found variable results in mutation frequency when using EMS within a crop suggest the use of alternative mutagens as a way for getting a higher density of mutations with less toxicity to the treated seeds [20]. Despite this higher mutation rate in the Charentais population, the efficiency of both populations in producing mutations predicted to be damaging to the proteins in Cm-eIF4E and Cm-PDS was similar. The new mutations found in Cm-eIF4E could be of interest, more so when this factor is highly conserved in eukaryotes. The natural diversity of Cm-eIF4E has been studied in melon and related species by EcoTILLING [31] and no variation has been reported within Cucumis melo, except for the nsv mutation (a point mutation of Leu228-His in exon 5), which controls resistance to Melon necrotic spot virus [44]. Variants in exons 1 to 3 were identified using EcoTILLING in another Cucumis species, Cucumis zeyheri, a wild relative of melon, isolated from the cultivated species by strong crossability barriers. Therefore, our new Cm-eIF4E alleles represent non-transgenic variants absent in nature. However it remains to be demonstrated if these mutations will lead to a gain of function, thereby producing new functional phenotypes, or to a loss of function. In other crops, recessive resistance to virus results from defective forms of eIF4E, for example in pepper (pvr2), pea (sbm1), tomato (pot-1), lettuce (mo1) and barley (rym) [45-47]. In most cases, resistance results from a few amino acid changes clustered in two neighboring regions of the eIF4E structure, located near the structural pocket involved in CAP-binding [48]. Some of the coding changes identified in our TILLING assay (in exons 1 and 2) are located near these two regions, close to the conserved tryptophan residues required for CAP-binding activity (Figure 5). The other coding mutations are found in different regions of the gene, but most affect highly conserved aminoacids. EcoTILLING has also shown that most natural variation in Cm-ACO1 occurs in exons 1, 2 and 3 [49]. No variants are found in large germplasm collections in exon 4. The effect of the identified mutation in exon 4 on ethylene production needs to be demonstrated. The mutants found in Cm-DET1 and Cm-DHS are the first reported for these genes in inodorus melons. It has been demonstrated that phenotypes of the tomato mutants high pigment-2dg (hp-2dg) and hp-2j are caused by lesions in the DET1 gene. Point missense mutations and intron mutations directing alternative splicing have been reported in both the N-terminus and the C-terminus of the protein in Arabidopsis and tomato, suggesting that both ends of the protein are important for this function [50,51]. It has been reported that suppression of DHS delays loss of tissue integrity in senescing tomato fruit, leading to an extended shelf life. Further analysis will indicate if melon mutants CmDET1 and Cm-DHS have alterations in fruit senescence. Segregation studies are now being performed along with phenotype analysis of the mutant lines. HGOm O (2)m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 Page 9 of 11 Figure 5 Localization of eIF4E amino acids differing between virus-susceptible and virus-resistant genotypes of pepper (Capsicum spp., pvr2), tomato (Lycopersicon spp., pot1), lettuce (Lactuca spp., mo1), pea (Pisum sativum, sbm1), melon (Cucumis melo, nsv) and barley (Hordeum vulgare, rym) in the predicted amino acid sequences (protein alignment of the susceptible genotypes). Black boxes indicate amino acids differing between susceptible and resistant genotypes. The two protein regions with clustering of amino acid substitutions are highlighted in pink and blue. In red are the mutations detected by TILLING in our PS population, in green, the mutations detected in the Charentais population. The conserved tryptophan residues reported to be required for cap-binding activity are underlined in the Pisum sequence [48]. Conclusions The TILLING approach worked in inodorus melons as a way of identifying new heritable variants in candidate genes that are different from those present in natural populations. The cosegregation of a mutation predicted to alter the functionality of PDS with the albino phenotype expected for PDS disruption suggests that this is a promising approach for advancement in reverse melon genetics. It is also useful to analyze TILLING populations phenotypically, in order to use the phenotypes of interest readily in crop improvement. The novel fruit phenotypes could be of interest to diversify the market supply of Piel HHFm de Sapo melons. The information presented here will also be useful for creating new inodorus melon populations with a higher mutation rate. Completion of the melon genome sequence will provide many potential target genes of interest that may be functionally studied, facilitating future genomic and breeding studies. Acknowledgements and Funding The authors thank Torben Jahrmann and Eulàlia Fitó (Semillas Fitó S.A.) for selfing the M1 plants and obtaining M3 seed from the M2 families, Fatima Dahmani for sequencing Cm-eIF4E/PS mutants, Montserrat Saladié for providing the sequences of Cm-ACO1 and Cm-NOR from the M62-113 melon line and Diego Bergareche for obtaining data on the M2 segregation. This (2)O m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 work was supported by projects GEN2003-20237-C06-02/03, funded by the Ministerio de Educación y Ciencia (Spain), and GEN2006-27773-C2-1/2, funded by the ERA-PG programme. Author details 1 IRTA, Centre de Recerca en Agrigenòmica CSIC-IRTA-UAB, Carretera de Cabrils Km 2, 08348 Cabrils (Barcelona), Spain. 2Institute for the Conservation and Breeding of Agricultural Biodiversity (COMAV-UPV), Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain. 3Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de València (UPV)-Consejo Superior de Investigaciones Científicas (CSIC), Ciudad Politécnica de la Innovación (CPI), Ed. 8E, C/Ingeniero Fausto Elio s/n, 46022 Valencia, Spain. 4Unité de Recherche en Génomique Végétale (INRA-URGV), 2 rue Gaston Crémieux CP 5708, 91057 Evry Cedex, France. 5Department of Plant Science, School of Agriculture and Biology, Shanghai Jiaotong University, 200030 Shanghai, People’s Republic of China. Authors’ contributions JG-M, MG and AJM performed the EMS mutagenesis. FN and BP contributed to the development and conservation of the M2 seed. BP, CR and CE extracted the DNA and performed the phenotypic analysis. DNA pooling, TILLING screens and analysis, and PDS mutant phenotypic analysis were done by MG, CT and MX. MX and MP participated in the sequencing of the eIF4E mutants in the M2 population. JG-M, AB, BP, and FN coordinated the study. BP, MG, CE, and JG-M were primarily responsible for drafting and revising the manuscript with contributions from co-authors. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 15 March 2011 Accepted: 11 August 2011 Published: 11 August 2011 References 1. The International Cucurbit Genomics Initiative (ICuGI). [http://www.icugi. org]. 2. González-Ibeas D, Blanca J, Roig C, González-To M, Picó B, Truniger V, Gómez P, Deleu W, Caño-Delgado A, Arús P, Nuez F, García-Mas J, Puigdomènech P, Aranda MA: MELOGEN: an EST database for melon functional genomics. BMC Genomics 2007, 8:306. 3. Fita A, Picó B, Monforte A, Nuez F: Genetics of Root System Architecture Using Near-isogenic Lines of Melon. J Am Soc Hortic Sci 2008, 133:448-458. 4. Fernandez-Silva I, Eduardo I, Blanca J, Esteras C, Picó B, Nuez F, Arús P, Garcia-Mas J, Monforte AJ: Bin mapping of genomic and EST-derived SSRs in melon (Cucumis melo L.). Theor Appl Genet 2008, 118:139-150. 5. Deleu W, Esteras C, Roig C, González-To M, Fernández-Silva I, Blanca J, Aranda MA, Arús P, Nuez F, Monforte AJ, Picó MB, Garcia-Mas J: A set of EST-SNPs for map saturation and cultivar identification in melon. BMC Plant Biol 2009, 9:90. 6. Mascarell-Creus A, Cañizares J, Vilarrasa J, Mora-García S, Blanca J, GonzálezIbeas D, Saladié M, Roig C, Deleu W, Picó B, López-Bigas N, Aranda MA, Garcia-Mas J, Nuez F, Puigdomènech P, Caño-Delgado A: An oligo-based microarray offers novel transcriptomic approaches for the analysis of pathogen resistance and fruit quality traits in melon (Cucumis melo L.). BMC Genomics 2009, 10:467. 7. Blanca JM, Cañizares J, Ziarsolo P, Esteras C, Mir G, Nuez F, Garcia-Mas J, Pico B: Melon transcriptome characterization. SSRs and SNPs discovery for high throughput genotyping across the species. Plant Genome 2011, 4(2):118-131. 8. González VM, Benjak A, Hénaff EM, Mir G, Casacuberta JM, Garcia-Mas J, Puigdomènech P: Sequencing of 6.7 Mb of the melon genome using a BAC pooling strategy. BMC Plant Biology 2010, 10:246. 9. Moreno E, Obando JM, Dos-Santos N, Fernández-Trujillo JP, Monforte AJ, Garcia-Mas J: Candidate genes and QTLs for fruit ripening and softening in melon. Theor Appl Genet 2007, 116:589-602. 10. Essafi A, Díaz-Pendón JA, Moriones E, Monforte AJ, Garcia-Mas J, MartínHernández AM: Dissection of the oligogenic resistance to Cucumber mosaic virus in the melon accession PI 161375. Theor Appl Genet 2009, 118:275-284. Page 10 of 11 11. Comai L, Henikoff S: TILLING: practical single-nucleotide mutation discovery. Plant J 2006, 45:684-94. 12. Cooper JL, Till BJ, Laport RG, Darlow MC, Kleffner JM, Jamai A, El-Mellouki T, Liu S, Ritchie R, Nielsen N, et al: TILLING to detect induced mutations in soybean. BMC Plant Biol 2008, 8(1):9. 13. Dalmais M, Schmidt J, Le Signor C, Moussy F, Burstin J, Savois V, Aubert G, de Oliveira Y, Guichard C, Thompson R, Bendahmane A: UTILLdb, a Pisum sativum in silico forward and reverse genetics tool. Genome Biol 2008, 9: R43. 14. Dierking EC, Bilyeu KD: New sources of soybean meal and oil composition traits identified through TILLING. BMC Plant Biol 2009, 9:89. 15. Perry J, Brachmann A, Welham T, Binder A, Charpentier M, Groth M, Haage K, Markmann K, Wang TL, Parniske M: TILLING in Lotus japonicus identified large allelic series for symbiosis genes and revealed a bias in functionally defective ethyl methanesulfonate alleles toward glycine replacements. Plant Physiol 2009, 151(3):1281-1291. 16. Caldwell DG, McCallum N, Shaw P, Muehlbauer GJ, Marshall DF, Waugh R: A structured mutant population for forward and reverse genetics in Barley (Hordeum vulgare L.). Plant J 2004, 40(1):143-150. 17. Henikoff S, Bradley JT, Comai L: TILLING. Traditional mutagenesis meets functional genomics. Plant Physiol 2004, 135:630-636. 18. Wu JL, Wu C, Lei C, Baraoidan M, Bordeos A, Madamba MR, RamosPamplona M, Mauleon R, Portugal A, Ulat VJ, et al: Chemical- and irradiation-induced mutants of indica rice IR64 for forward and reverse genetics. Plant Mol Biol 2005, 59(1):85-97. 19. Slade AJ, Fuerstenberg SI, Loeffler D, Steine MN, Facciotti D: A reverse genetic, nontransgenic approach to wheat crop improvement by TILLING. Nat Biotechnol 2005, 23:75-81. 20. Till BJ, Cooper J, Tai TH, Colowit P, Greene EA, Henikoff S, Comai L: Discovery of chemically induced mutations in rice by TILLING. BMC Plant Biol 2007, 7:19. 21. Xin Z, Wang ML, Barkley NA, Burow G, Franks C, Pederson G, Burke J: Applying genotyping (TILLING) and phenotyping analyses to elucidate gene function in a chemically induced sorghum mutant population. BMC Plant Biol 2008, 8:103. 22. Dong C, Dalton-Morgan J, Vincent K, Sharp P: A modified TILLING method for wheat breeding. Plant Genome 2009, 2:39-47. 23. Sestili F, Botticella E, Bedo Z, Phillips A, Lafiandra D: Production of novel allelic variation for genes involved in starch biosynthesis through mutagenesis. Mol Breeding 2010, 25:145-154. 24. Watanabe S, Mizoguchi T, Aoki K, Kubo Y, Mori H, Imanishi S, Yamazaki Y, Shibata D, Ezura H: Ethylmethanesulfonate (EMS) mutagenesis of Solanum lycopersicum cv. Micro-Tom for large-scale mutant screens. Plant Biotech 2007, 24:33-38. 25. Elias R, Till BJ, Mba Ch, Al-Safadi B: Optimizing TILLING and Ecotilling techniques for potato (Solanum tuberosum L). BMC Res Notes 2009, 2:141. 26. Piron F, Nicolaı M, Minoıa S, Piednoir E, Moretti A, Salgues A, Zamir D, Caranta C, Bendahmane A: An induced mutation in tomato eIF4E leads to immunity to two Potyviruses. PLoS ONE 2010, 5(6):e11313. 27. Himelblau E, Gilchrist EJ, Buono K, Bizell C, Mentzer L, Vogelzang R, Osborn T, Amasino RM, Parkin IAP, Haughn : Forward and reverse genetics of papid cycling Brassica oleracea. Theor Appl Genet 2009, 118:953-961. 28. Stephenson P, Baker D, Girin T, Perez A, Amoah S, King GJ, Østergaard L: A rich TILLING resource for studying gene function in Brassica rapa. BMC Plant Biol 2010, 10:62. 29. Pitrat M: Melon (Cucumis melo L.). In Handbook of Crop Breeding Vol I. Vegetables. Edited by: Prohens J, Nuez F. New York:Springer; 2008:283-315. 30. Dahmani-Mardas F, Troadec Ch, Boualem A, Leveque S, Alsadon AA, Aldoss AA, Dogimont C, Bendahman A: Engineering Melon Plants with Improved Fruit Shelf Life Using the TILLING Approach. PLoS ONE 2010, 5: e15776. 31. Nieto C, Piron F, Dalmais M, Marco CF, Moriones E, Gómez-Guillamón ML, Truniger V, Gómez P, Garcia-Mas J, Aranda MA, Bendahmane A: EcoTILLING for the identification of allelic variants of melon eIF4E, a factor that controls virus susceptibility. BMC Plant Biol 2007, 7:34. 32. Qin G, Gu H, Ma L, Peng Y, Deng XW, Chen Z, Qu LJ: Disruption of phytoene desaturase gene results in albino and dwarf phenotypes in Arabidopsis by impairing chlorophyll, carotenoid, and gibberellin biosynthesis. Cell Res 2007, 17:471-482. 33. Codons Optimized to Deliver Deleterious Lesions (CODDLe). [http://www. proweb.org/input]. HHGm O (2)m González et al. BMC Research Notes 2011, 4:289 http://www.biomedcentral.com/1756-0500/4/289 Page 11 of 11 34. Lasserre E, Bouquin T, Hernández JA, Bull J, Pech JC, Balague C: Structure and expression of three genes encoding ACC oxidase homologs from melon (Cucumis melo L.). Mol Gen Genet 1996, 251(1):81-90. 35. Giovannoni JJ: Fruit ripening mutants yield insights into ripening control. Curr Opin Plant Biol 2007, 10:1-7. 36. Davuluri GR, van Tuinen A, Mustilli AC, Manfredonia A, Newman R, Burgess D, Brummell DA, King SR, Palys J, Uhlig J, Pennings HMJ, Bowler C: Manipulation of DET1 expression in tomato results in photomorphogenic phenotypes caused by post-transcriptional gene silencing. Plant J 2004, 40:344-354. 37. Wei S, Li X, Gruber MI, Li R, Zhou R, Zebarjadi A, Hannoufa A: RNAimediated suppression of DET1 alters the levels of carotenoids and sinapate esters in seeds of Brassica napus. J Agric Food Chem 2009, 57(12):5326-5333. 38. Wang TW, Zhang CG, Wu W, Nowack LM, Madey E, Thompson JE: Antisense suppression of deoxyhypusine synthase in tomato delays fruit softening and alters growth and development DHS mediates the first of two sequential enzymatic reactions that activate eukaryotic translation initiation factor-5A. Plant Physiol 2005, 138:1372-1382. 39. Ng PC, Henikoff S: SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res 2003, 31(13):3812-3814. 40. Guzman P, Ecker JR: Exploiting the triple response of Arabidopsis to identify ethylene-related mutants. The Plant Cell 1990, 2:513-523. 41. Henikoff S, Comai L: Single-nucleotide mutations for plant functional genomics. Ann Rev Plant Biol 2003, 54:375-401. 42. Greene EA, Codomo CA, Taylor NE, Henikoff JG, Till BJ, Reynolds SH, Enns LC, Burtner C, Johnson JE, Odden AR, et al: Spectrum of chemically induced mutations from a large-scale reverse genetic screen in Arabidopsis. Genetics 2003, 164(2):731-740. 43. Britt AB: DNA damage and repair in plants. Annu Rev Plant Physiol Plant Mol Biol 1996, 47:75-100. 44. Truniger V, Nieto C, González-Ibeas D, Aranda M: Mechanism of plant eIF4E-mediated resistance against a Carmovirus (Tombusviridae): capindependent translation of a viral RNA controlled in cis by an (a) virulence determinant. Plant J 2008, 56(5):716-727. 45. Gao Z, Johansen E, Eyers S, Thomas CL, Ellis THN, Maule AJ: The potyvirus recessive resistance gene, sbm1, identifies a novel role for translation initiation factor eIF4E in cell-to-cell trafficking. Plant J 2004, 40(3):376-385. 46. Kang BC, Yeam I, Frantz JD, Murphy JF, Jahn MM: The pvr1 locus in Capsicum encodes a translation initiation factor eIF4E that interacts with Tobacco etch virus VPg. Plant J 2005, 42(3):392-405. 47. Ruffel S, Gallois J, Lesage M, Caranta C: The recessive potyvirus resistance gene pot-1 is the tomato orthologue of the pepper pvr2-eiF4 genes. Mol Genet Genom 2005, 274(4):346-353. 48. Nicaise V, German-Retana S, Sanjuán R, Dubrana MP, Mazier M, Maisonneuve B, Candresse T, Caranta C, LeGall O: The Eukaryotic Translation Initiation Factor 4E Controls Lettuce Susceptibility to the Potyvirus Lettuce mosaic virus1. Plant Physiol 2003, 132:1272-1282. 49. Esteras C, Pascual L, Saladie M, Dogimont C, Garcia-Mas J, Nuez F, Picó B: Use of Ecotilling to identify natural allelic variants of melon candidate genes involved in fruit ripening. Proceedings Plant GEM8 Lisbon 2009. 50. Levin I, Frankel P, Gilboa N, Tanny S, Lalazar A: The tomato dark green mutation is a novel allele of the tomato homolog of the DEETIOLATED1 gene. Theor Appl Genet 2003, 106:454-460. 51. Kolotilin I, Koltai H, Tadmor Y, Bar-Or C, Reuveni M, Meir A, Nahon S, Shlomo S, Chen L, I Levin: Transcriptional profiling of high pigment-2dg tomato mutant links early fruit plastid biogenesis with its overproduction of phytonutrients. Plant Physiol 2007, 145:389-401. doi:10.1186/1756-0500-4-289 Cite this article as: González et al.: Towards a TILLING platform for functional genomics in Piel de Sapo melons. BMC Research Notes 2011 4:289. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit T HHHm T (2)O m T BMC Genomics BioMed Central Open Access Research article MELOGEN: an EST database for melon functional genomics Daniel Gonzalez-Ibeas1, José Blanca2, Cristina Roig2, Mireia González-To3, Belén Picó2, Verónica Truniger1, Pedro Gómez1, Wim Deleu3, Ana Caño-Delgado4, Pere Arús3, Fernando Nuez2, Jordi Garcia-Mas3, Pere Puigdomènech4 and Miguel A Aranda*1 Address: 1Departamento de Biología del Estrés y Patología Vegetal, Centro de Edafología y Biología Aplicada del Segura (CEBAS)- CSIC, Apdo. correos 164, 30100 Espinardo (Murcia), Spain, 2Departamento de Biotecnología, Instituto de Conservación y Mejora de la Agrodiversidad Valenciana (COMAV-UPV), Camino de Vera s/n, 46022 Valencia, Spain, 3Departament de Genètica Vegetal, Centre de Recerca en Agrigenòmica CSIC-IRTA, Carretera de Cabrils Km2, 08348 Cabrils (Barcelona), Spain and 4Departament de Genètica Molecular, Centre de Recerca en Agrigenòmica CSIC-IRTA, Jordi Girona 18-26, 08034 Barcelona, Spain Email: Daniel Gonzalez-Ibeas - [email protected]; José Blanca - [email protected]; Cristina Roig - [email protected]; Mireia GonzálezTo - [email protected]; Belén Picó - [email protected]; Verónica Truniger - [email protected]; Pedro Gómez - [email protected]; Wim Deleu - [email protected]; Ana Caño-Delgado - [email protected]; Pere Arús - [email protected]; Fernando Nuez - [email protected]; Jordi Garcia-Mas - [email protected]; Pere Puigdomènech - [email protected]; Miguel A Aranda* - [email protected] * Corresponding author Published: 3 September 2007 BMC Genomics 2007, 8:306 doi:10.1186/1471-2164-8-306 Received: 8 May 2007 Accepted: 3 September 2007 This article is available from: http://www.biomedcentral.com/1471-2164/8/306 © 2007 Gonzalez-Ibeas et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Melon (Cucumis melo L.) is one of the most important fleshy fruits for fresh consumption. Despite this, few genomic resources exist for this species. To facilitate the discovery of genes involved in essential traits, such as fruit development, fruit maturation and disease resistance, and to speed up the process of breeding new and better adapted melon varieties, we have produced a large collection of expressed sequence tags (ESTs) from eight normalized cDNA libraries from different tissues in different physiological conditions. Results: We determined over 30,000 ESTs that were clustered into 16,637 non-redundant sequences or unigenes, comprising 6,023 tentative consensus sequences (contigs) and 10,614 unclustered sequences (singletons). Many potential molecular markers were identified in the melon dataset: 1,052 potential simple sequence repeats (SSRs) and 356 single nucleotide polymorphisms (SNPs) were found. Sixty-nine percent of the melon unigenes showed a significant similarity with proteins in databases. Functional classification of the unigenes was carried out following the Gene Ontology scheme. In total, 9,402 unigenes were mapped to one or more ontology. Remarkably, the distributions of melon and Arabidopsis unigenes followed similar tendencies, suggesting that the melon dataset is representative of the whole melon transcriptome. Bioinformatic analyses primarily focused on potential precursors of melon micro RNAs (miRNAs) in the melon dataset, but many other genes potentially controlling disease resistance and fruit quality traits were also identified. Patterns of transcript accumulation were characterised by Real-Time-qPCR for 20 of these genes. Conclusion: The collection of ESTs characterised here represents a substantial increase on the genetic information available for melon. A database (MELOGEN) which contains all EST sequences, contig images and several tools for analysis and data mining has been created. This set of sequences constitutes also the basis for an oligo-based microarray for melon that is being used in experiments to further analyse the melon transcriptome. HHIm O (2)m Background Melon (Cucumis melo L.) is an important horticultural crop grown in temperate, subtropical and tropical regions worldwide. Melon is among the most important fleshy fruits for fresh consumption, its total production in 2004 exceeding 874 million metric tons, of which 72.5% are produced in Asia, 11.7% in Europe, 8.4% in America and 6.1% in Africa, being a significant component of fresh fruit traded internationally [1]. Melon belongs to the Cucurbitaceae family, which comprises up to 750 different species distributed in 90 genera. Species in this family include watermelon, cucumber, squash and marrow, all of them cultivated essentially because of their fruits, but this family also includes species of interest for other reasons, as, for example, their contents in potentially therapeutic compounds (e.g. Momordica charantia) [2]. Melon is a diploid species, with a basic number of chromosomes x = 12 (2x = 2n = 24) and an estimated genome size of 450 to 500 Mb [3], similar in size to the rice genome (419 Mb) [4,5] and about three times the size of the Arabidopsis genome (125 Mb) [6]. Melon has been classified into two subspecies, C. melo ssp. agrestis and C. melo ssp. melo with India and Africa being their centres of origin, respectively [7,8]. Melon has a great potential for becoming a model for understanding important traits in fruiting crops. Melon fruits have wide morphological, physiological and biochemical diversity [7,9] which can be exploited to dissect biological processes of great technological importance, among them flavour development and textural changes that occur during fruit ripening. The contemporary melon cultivars can be divided into two groups, climacteric and nonclimacteric, according to their ripening patterns [10]. Climacteric fruits are characterized by rapid and profound changes during ripening associated to increased levels of respiration and release of ethylene, whereas the nonclimacteric varieties do not produce ethylene and have long shelf-life. Analyses of climacteric and nonclimacteric melons have illustrated the process of aroma formation [1114] and the temporal sequence of cell wall disassembly [15-17]. Melon can be also a very useful experimental system to analyse other aspects of fundamental plant biology. For example, melon and other cucurbits have been used to analyse the development of the plant vasculature and the transportation of macromolecules through it [1820], and different interactions between melon and pests and pathogens have been characterised with varying depths [21-27]. Important genetic tools have been described for melon, as for example linkage genetic maps [28,29] and the development of a genomic library of near isogenic lines (NILs) from an exotic accession [30]; also, biotechnology is feasible in melon [31-33]. However, the great majority of genes involved in the aforementioned traits are yet to be identified in melon. Partial sequencing of cDNA inserts of expressed sequence tags (ESTs) have been used as an effective method for gene discovery. By sequencing clones derived from RNA from different sources, and/or by normalizing cDNA libraries, the total set of genes sampled can be maximized. Bioinformatic analysis, annotation and clustering of sequences could yield databases which mining can be used to select candidate genes implicated in traits of interest. EST collections can also serve to construct microarrays useful for identifying sets of plant genes expressed during different developmental stages and/or responding to environmental stimuli [34,35]. In addition, EST collections are good sources of simple sequence repeats (SSRs) and single-nucleotide polymorphisms (SNPs) that can be used for creating saturated genetic maps [36,37]. Thus, EST collections have been generated for many plant species, being the most comprehensive those of Arabidopsis[6] and rice [38]. Fruit crops have been less extensively surveyed, but important collections are publicly available for several species, including tomato [39], apple [40], grape [41] and citrus [42]. Despite the importance of the family Cucurbitaceae, relatively little EST information is currently available: only 16,039 nucleotide sequences have been annotated from the whole Cucurbitaceae family in the publicly accessible GenBank database as of November 2006; out of these, 12,180 correspond to the Cucumis genus and 6,061 to melon. These numbers are in sharp contrast with the data available for families composed of other important food crops like Solanaceae (1,020,102 sequences), Fabaceae (1,466,518 sequences), Brassicaceae (1,010,148 sequences excluding Arabidopsis), Vitaceae (449,478) and Rosaceae (390,066 sequences). Here we describe a public EST sequencing project in melon. We report the determination and analysis of 30,675 high-quality melon ESTs, sequenced from eight normalized cDNA libraries corresponding to different tissues in different physiological conditions. We have classified the sequences into functional categories and described SSRs and SNPs of potential use in genetic maps and marker-assisted breeding programs. A database which contains all EST sequences, contig images and several tools for analysis and data mining has been created. In addition, we have analyzed the EST melon dataset to identify candidate genes potentially coding microRNAs or involved in fruit maturation processes and pathogen defence. The pattern of transcript accumulation in different physiological conditions has been characterised by Real-Time-qPCR for 20 of these candidate genes. HHJm T (2)O m Results EST Sequencing and Clustering Eight cDNA libraries were constructed using material from "Piel de Sapo" Spanish cultivars, the C-35 cantaloupe line (both belonging to Cucumis melo L. ssp. melo) and the accession pat81 of C. melo L. ssp. agrestis (Naud.) Pangalo. The sources of RNA to construct each library were fruits of 15 and 46 days after pollination (dap), leaves, photosynthetic cotyledons inoculated with Cucumber mosaic virus (CMV), healthy roots and Monosporascus cannonballus Pollack et Uecker (the causal agent of melon vine decline) infected roots (Table 1). Approximately 3,700 sequences were determined from each library by single-pass 5' sequencing, except for the library prepared from CMV infected cotyledons for which approximately 6,600 sequences were determined, yielding a total of 33,292 raw sequences. Processing to eliminate vector sequences, low quality chromatograms and sequences of less than 100 base pairs (bp) gave rise to 29,604 good quality expressed sequence tags (ESTs) (Table 2) implying a cloning success of approximately 89%. The average edited length was 674 bp, and only a 6.4% of the sequences had less than 350 bp. Clustering of the sequences using default parameters of the EST analysis pipeline EST2uni [43] yielded 6,023 tentative consensus sequences (also called contigs) and 10,614 unclustered sequences (also called singletons), with a total of 16,637 non-redundant sequences or unigenes (Table 2). All good quality ESTs were used for clustering, independently of the melon genotype of origin, because single nucleotide polymorphisms (SNPs) were expected among genotypes. The number of ESTs per unigene was between 1 and 44 (1 case), with an average of 1.8 ESTs per contig, as a high proportion of contigs (4,886 out of 6,023) contained less than 5 ESTs and contigs with more than 8 ESTs were scarce (Fig. 1A). Therefore, redundancy values were notably low (around 16%). The unigene length varied between 101 bp and 2,664 bp, averaging 751 bp (Fig. 1B). Library specific unigenes were about one third of the total for each library (Table 2). A second round of clustering yielded 14,480 unigene clusters, referred to as superunigenes. A web integrated data- base that contains all EST sequences, contig images and several tools for analysis and data mining has been created and named MELOGEN [44]. Codon usage was estimated using this EST collection. As expected, the codon usage of melon was very similar to that of Arabidopsis and other dicots. The preferred stop codon was UGA occurring in the 48% of the sequences. Suppression of the CG dinucleotide in the last two codon positions is very frequent in dicots, possibly as a consequence of methylation of C in the CG dinucleotide, resulting in an increased mutation rate [45]; in agreement with these data, the ratio XCG/ XCC for melon was 0.52, very similar to the corresponding figure for tomato (0.58), pea (0.51), potato (0.48) and other dicots [45]. Libraries obtained from tissues inoculated with M. cannonballus were expected to contain sequences from the fungus. To estimate the proportion of sequences of fungal origin in these libraries, BLAST analyses against a database with plant and fungal sequences were carried out [46]. Only 56 sequences from these libraries were found to have a more significant similarity with fungal sequences than with plant sequences (Table 3). Consequently, these sequences were considered of fungal origin [46]. SSRs and SNPs We have analysed the nature and frequency of microsatellites or simple sequence repeats (SSRs) in the melon sequence dataset. A search for repeats of two, three or four nucleotides in the dataset yielded 1,052 potential SSRs. Approximately, 6% of the unigenes contained at least one of the considered SSRs motifs, with repeats of three nucleotides being prevalent (Table 4). The maximum and minimum lengths of the repeats were 68 and 17 nucleotides, respectively, and the average length was 26 nucleotides. The most common repeat among dinucleotides was, by far, the AG repeat, constituting the 83% (Table 4). Repeats of AT and AC dinucleotides followed, with approximately 9% and 7%, respectively. Among the trinucleotide repeats, the most frequent was AAG (66%, Table 4), and the least frequent was ACT (0.6%, Table 4). Among tetranucleotide repeats, the most frequent was AAAG (51%, Table 4). A high proportion of SSRs (29.5%) Table 1: Description of cDNA libraries Name Subspecies/cultivar/accession Tissue/physiological condition 15d 46d A AI CI HS PS PSI Ssp. melo cv. "Piel de Sapo" T-111 Ssp. melo cv. "Piel de Sapo" T-111 Ssp. agrestis accession pat81 Ssp. agrestis accession pat81 Ssp. melo var. cantaloupe accession C-35 Ssp. melo var. cantaloupe accession C-35 Ssp. melo cv. "Piel de Sapo" Piñonet torpedo Ssp. melo cv. "Piel de Sapo" Piñonet torpedo Fruit 15 days after pollination Fruit 46 days after pollination Roots Roots infected with M. cannonballus Photosynthetic cotyledons infected with CMV Leaves Roots Roots infected with M. cannonballus HHKm O (2)m Table 2: EST statistics Library Raw sequences Good-Quality ESTs EST length Singletons Contigs Unigenes Redundancy (%) Library-specific unigenes Novelty (%) 15d 46d A AI CI HS PS PSI 3,936 3,840 3,936 3,647 6,605 3,648 3,840 3,840 33,292 3,582 3,493 3,666 3,255 5,664 3,012 3,377 3,555 29,604 608.1 ± 175.2 583.0 ± 161.1 700.0 ± 185.4 756.3 ± 137.1 651.4 ± 205.7 669.3 ± 171.1 679.9 ± 198.7 749.3 ± 156.2 1,009 1,000 1,289 928 2,089 939 1,179 1,279 10,614 1,930 1,854 1,900 1,688 2,590 1,609 1,766 1,826 6,023 2,939 2,854 3,189 2,616 4,679 2,548 2,945 3,105 16,637 18 18 13 20 17 15 13 13 1,100 1,063 1,365 1,005 2,264 998 1,258 1,363 37 37 43 38 48 39 43 44 were found in open reading frames (ORFs), though an analysis of the localization of di-, tri- and tetranucleotides separately showed that di- and tetranucleotides localised preferentially in untranslated regions (UTRs), whereas trinucleotides localised in both, UTRs and ORFs (Table 5). Single nucleotide polymorphisms (SNPs) are the most abundant variations in genomes and, therefore, constitute a powerful tool for mapping and marker-assisted breeding. We initially identified in the melon sequence dataset 14,074 single nucleotide sequence variations and therefore potential SNPs (pSCH; Table 6) distributed in 4,663 contigs; however, these variations would include highquality SNPs (pSNP) but also sequencing errors and mutations introduced during the cDNA synthesis step. Using more stringent criteria, these figures were substantially reduced: Putative SNPs were annotated only when the least represented allele was present in at least two EST sequences from the same genotype in a given contig and showing the same base change. Two accessions of the same cultivar (cv. "Piel de sapo") represented 47.3% of the sequences, but more than one half of the sequences were from two other more distant genotypes, the C-35 cantaloupe accession (29.3%) and the pat81 agrestis accession (23.4%). Thus, a total of 356 high-quality SNPs were found in 292 contigs, averaging 1.2 SNPs per contig. Table 3: ESTs showing significant similarity with fungal sequences Library Number of ESTs 15d 46d A AI CI HS PS PSI Total 0 0 2 26 0 1 1 30 60 Transitions were much more common than transversions. There were 117 AG and 112 CT transitions compared with 28 AC, 37 AT and 33 GT transversions (Table 6). CG transversions were not detected. The MELOGEN database [44] includes a tool for designing oligonucleotide primers to amplify the region containing the polymorphism to generate the corresponding molecular marker. Functional annotation In order to identify melon unigenes potentially encoding proteins with known function, we carried out a BLASTX analysis [47] of the sequence dataset against the databases listed in Table 7. Out of the 13,019 unigenes with a hit with proteins in databases, 11,431 (68.7%) unigenes showing an E value of 1e-10 were annotated. On the other hand, 31.3% of the unigenes did not show significant similarity to any protein in the databases and, therefore, were not annotated. Additionally, we performed a functional classification of the unigenes following the Gene Ontology scheme. Gene Ontology provides a structured and controlled vocabulary to describe gene products according to three ontologies: molecular function, biological process and cellular component [48]. To do that, we added GO terms based on the automated annotation of each unigene using the Arabidopsis database [6]. A summary of the results with the percentage of unigenes annotated in representative categories corresponding to the GO slim terms [48] is shown, as well as a comparison of the distribution of melon and Arabidopsis unigenes (Fig. 2). The distributions of melon and Arabidopsis unigenes follow similar tendencies, suggesting that the melon dataset is representative of the whole melon transcriptome. In total, 9,402 unigenes could be mapped to one or more ontologies, with multiple assignments possible for a given protein within a single ontology. A high percentage of unigenes in both species was classified as "unknown function". Out of the 9,791 assignments made to the cellular component category, 25.8% corresponded to membrane proteins and 17.8% to plastidial proteins (Fig. 2A). Under the molecu- HHLm (2)O m !!! Table 4: Simple sequence repeats (SSRs) statistics* Number of di-pSSR % AG AT AC Total 205 23 18 246 83.3 9.4 7.3 100 Dinucleotide repeat Figure 1 statistics Unigenes Unigenes statistics. (A) Distribution of melon ESTs among unigenes (contigs and singletons). (B) Size distribution of melon unigenes. lar function category, assignments were mainly to catalytic activity (23.0%) and to hydrolase activity (14.7%) (Fig. 2B). The distribution of unigenes under the biological process category was more uniform, with 19.9% of assignments to cellular process and 12.7% to biosynthesis (Fig. 2C). We have also identified 6,673 (40.1%) melon unigenes with an ortholog in the Arabidopsis database, and a HMMER motif has been assigned to 4,655 (28.0%) unigenes by comparisons with the Pfam database [49] (Table 7). All these results are compiled in the MELOGEN database, which also contains direct links to the databases used to carry out analyses. Genes potentially encoding microRNAs Central to RNA silencing are small RNA molecules (sRNAs) that can arise from endogenous or exogenous sources from precursors with double-stranded RNA (dsRNA) pairing. One class of such sRNAs are microRNAs (miRNAs), which originate from endogenous long selfcomplementary precursors that mature in a multi-step process involving many enzymes [50,51]. Recently, a Trinucleotide repeat Number of tri-pSSR % AAC AAG AAT ACC ACG ACT AGC AGG ATC CCG Total 41 471 22 18 14 4 25 54 48 17 714 5.7 66.0 3.1 2.5 2.0 0.6 3.5 7.6 6.6 2.4 100 Tetranucleotide repeat Number of tetra-pSSR % AAAC AAGG AATC AATG AATT ATCG ACTC AAGC ACAT AAAG AAAT Total 8 7 4 3 2 2 1 1 1 47 16 92 8.7 7.6 4.3 3.3 2.2 2.2 1.1 1.1 1.1 51.1 17.3 100 *The number of di-, tri- and tetranucleotide repeats identified in the melon database is shown for the complete set of putative SSRs (pSSRs). comprehensive strategy to identify new miRNA homologs in EST databases has been developed [52,53]. We have followed this strategy to identify potential melon miRNAs. A total of 20 ESTs that contained homologs to miRNAs in the microRNA Registry database [54] were identified and grouped into 12 contigs and, after manual inspection of secondary foldback hairpin structure, 5 unigenes were selected (Table 8). Contig sequences varied between 536 and 840 nucleotides long, and had negative folding free energies of -206.8 to -160.8 kcal mol-1 (Table 8) according to MFOLD [55], which are in the range of the computational values of Arabidopsis miRNA precursors [52]. Their predicted secondary structures showed that there were at least 16 nucleotides paired between the sequence of the potential mature miRNA and its opposite arm (miRNA*) in the corresponding hairpin structure (Fig. 3). The location of the potential miRNAs varied among ESTs, 4 were found in the sense orientation of the EST, 1 was found in HHMm O (2)m Table 5: Localization of simple sequence repeats (SSRs) with respect to putative initiation and termination codons in the melon sequence dataset* 5'-UTR ORF 3'-UTR Other† Total Dinucleotide repeats Trinucleotide repeats Tetranucleotide repeats All SSRs analyzed No. % No. % No. % No. % 65 0 13 1 79 82.3% 0.0% 16.5% 1.3% 100.0% 121 99 13 1 234 51.7% 42.3% 5.6% 0.4% 100.0% 18 2 9 0 29 62.1% 6.9% 31.0% 0.0% 100.0% 204 101 35 2 342 59.6% 29.5% 10.2% 0.6% 100% *Only full length melon unigenes were used for this analysis. Full length unigenes were automatically selected by checking the presence of the start codon by comparison of the 5'-terminal region of the unigene with the corresponding Arabidopsis gene used for annotation. †Imprecise localization of the SSR with respect to putative initiation or termination codons. the antisense orientation. We have also searched for potential targets of the potential miRNAs in the melon EST dataset, identifying 3 of them (Table 8). However, minimal folding free energy indexes (MFEIs) [53] were below the -0.85 cut-off value proposed by Zhang et al. [53] only for m12 (Table 8). Potential melon miRNA m12 has a precursor of 536 nt in length and codes for a melon ortholog of the Arabidopsis miR319. miR319 targets a transcription factor of the TCP family [56,57]; in the melon dataset, an ortholog of this Arabidopsis gene has been found in a unigene annotated as a TCP transcription factor. In this case, the melon miRNA and its potential target have a pattern of paired/non-paired bases between the target and the miRNA identical to the corresponding target-miRNA pattern in Arabidopsis (data not shown). Genes potentially encoding pathogen resistance and fruit quality traits Pathogens affect severely the productivity of melon crops. Three of the cDNA libraries sequenced here correspond to pathogen-infected tissues and, thus, should contain transcripts from genes whose expression is induced in response infection. We have carried out a bioinformatics search for homologs of genes involved in pathogen resistance response (see [58] for a review) and virus susceptibility [59-61], finding among them at least one melon ortholog to the Arabidopsis FLS2 receptor [62], several unigenes potentially encoding disease resistance proteins as well as mitogen-activated protein kinases, homologs to translation initiation factors constituting potential virus susceptibility factors, etc. [see Additional file 1]. Fruit development and ripening are the most important processes determining the fruit quality traits of fleshy fruits like melon. At present most of the molecular and genetic data available about fruit development and ripening come from tomato [63,64] and Arabidopsis [65,66]. In recent years, several genes and quantitative trait loci controlling fruit quality traits have been described in melon [67,68]. As for developmental processes, homologs to genes involved in melon fruit development, ripening and quality have been found in the melon dataset. These include several MADS-box genes, homologs to the fw2.2 and ovate QTLs [69,70], several homologs to Table 6: Single nucleotide polymorphisms (SNPs) statistics* Variation Number % pSNP transversions: pSNP transitions: pSCH transversions: pSCH transitions: 127 229 4,273 9,801 35.7 64.3 30.4 69.6 Mutation Number of pSNP Mutation Number of pSCH A<->C A<->G A<->T C<->G C<->T G<->T 28 117 37 29 112 33 A<->C A<->G A<->T C<->G C<->T G<->T 859 5,860 1,897 431 3,941 1,086 *Type and number of transition and transversions are shown for putative single nucleotide variations in sequence (pSCH) and for putative highquality single nucleotide polymorphism (pSNP) identified in the melon database. HHNm (2)O m Table 7: Functional annotation statistics A. Number of unigenes with BLAST hits Database* Number of unigenes % Arabidopsis Cucurbitaceae Uniref90 Any database 11,724 5,340 11,893 13,019 70.5 32.1 71.5 78.3 Database* Number of unigenes % Pfam 4,655 28.0 Database* Number of unigenes % Arabidopsis 6,673 40.1 B. Number of unigenes with HMMER hits C. Number of unigenes with orthologue * Databases searched were: Arabidopsis [6,109]; Uniref90 [110,115]; Cucurbitaceae: all cucurbitaceae sequences available in the National Center for Biotechnology Information (NCBI); any database: results using Arabidopsis, cucurbitaceae and Uniref90 databases all together; Pfam [49,112]. members of the SBP-box gene family to which the major tomato ripening gene COLORLESS NON-RIPENING belongs [71], several ACC synthase and ACC oxidase genes, unigenes from several cell wall-metabolism enzymes, etc [see Additional file 1]. Expression analysis of selected ESTs by Real-Time-qPCR The accumulation of transcripts for 20 selected genes was analyzed by reverse transcription Real-Time-qPCR. ESTs for this analysis were preferentially chosen among those showing significant similarity with genes related to response to infection and fruit quality characteristics in melon and other species, and included CTL1, EIF4A-2, EIF4E, EIN4, GA2OX1, HSP101, HSP70, IAA9, LSM1, LUT2, NCBP, SVP, HIR, TCH4, TIP4, TOM1, TOM2A, TOM3, UGE5 and WRKY70 (Table 9). Preliminary experiments were carried out to choose between GAPDH and CYCLOPHILIN (CYP7) RNAs as endogenous controls; results showed that the CYP7 RNA levels varied the least among treatments (data not shown) and, therefore, transcript accumulation levels were expressed relative to CYP7 RNA levels. Figure 4A illustrates the alteration of the RNA accumulation levels of selected genes that occurred in photosynthetic cotyledons after CMV infection. A significant increase in the level of transcripts from HSP101, HSP70, HIR, TOM2A, WRKY70 and EIN4 was observed; for HSP101, HSP70, WRKY70 and EIN4, transcript accumulation levels in inoculated cotyledons were up to five times greater than in uninoculated controls (Fig. 4A). All of these genes, except TOM2A, have been shown to be responsive to virus infection in other hosts [72-74]. Notably, the expression of EIF4E, known to be required for MNSV multiplication [27], remained unaltered. A shutoff of host gene expression also occurs in association with virus infection [75]; for the set of genes analysed here, only GA2OX1 and NCBP responded to CMV infection with a reduction in the accumulation of their transcripts. The response of selected genes in roots inoculated with M. cannonballus was analysed in melon genotypes known to be susceptible (cultivar "Piel de sapo"; Fig. 4B) and partially resistant (accession pat81 of C. melo L. ssp. agrestis; Fig. 4C) to the infection by this fungus. The patterns of transcript accumulation resulted clearly different for both genotypes. For pat81 (resistant), transcription factors WRKY70 and SVP increased their expression between 2 and 3 times after inoculation; other stress-inducible genes (HSP101, HSP70) showed only a moderate increase (Fig. 4C). For "Piel de sapo" (susceptible), accumulation of WRKY70 and SVP transcripts only increased about 1.5 times after inoculation whereas the expression of HSP101 showed a marked increase (Fig. 4B). It is also worth noting the differential response of the GA2OX1 gene in the two genotypes. Expression of GA2OX1 increased about 1.5 times in pat81 roots after the M. cannonballus attack, whereas it decreased in "Piel de sapo" roots after fungal infection (compare Figs. 4B and 4C). Comparison of patterns of transcript accumulation at two stages of fruit development showed increased levels of HHOm ( HIFm %% * #$! % % * * % % #$! % % % &$! % % O (2)m ! " ! " ) ' ! " products2 of melon and Arabidopsis unigenes according to the Gene Ontology scheme for functional classification of gene Distribution Figure Distribution of melon and Arabidopsis unigenes according to the Gene Ontology scheme for functional classification of gene products. (2)O m !!! Table 8: Potential melon miRNAs Name Potential mature miRNA sequence (5'->3')* Melogen unigene† Precursor folding free energy (kcal mol-1)§ MFEI (kcal mol-1) miRNA family Potential target in melon m2 m4 m7 m8 m12 ugaagcugccagcaugaucu ugauugagccgugccaauauc ucggaccaggcuucauucccc uugacagaagauagagagcac uuggacugaagggagcucccu bCL2353Contig1 bPSI_40-F10-M13R_c bA_31-D02-M13R_c bCI_04-H02-M13R_c b15d_24-H05-M13R_c -206.8 -195.0 -160.8 -188.2 -163.6 -0.67 -0.66 -0.70 -0.74 -0.86 miR167 miR171 miR166 miR157 miR319 -bHS_39-C12-M13R_c -bCI_30-A09-M13R_c bCL2243Contig1 *Nucleotide sequences correspond to potential mature miRNA sequences as deduced from BLAST searches using known plant miRNA sequences [54] and analysis of secondary structure predictions [52]. †Accession numbers (MELOGEN database) of potential precursors of melon miRNAs are given. §Computational values of folding free energies have been calculated using MFOLD 3.1 [55]. Minimal folding free energy indexes (MFEIs) have been calculated as described by Zhang et al. [53]. gene expression for 9 of the analysed genes. This was particularly evident for HSP70, TOM2A, TOM3, EIN4 and IAA9. In contrast, decreased levels of transcript accumulation were observed for the other 11 genes. genes for experiments aimed at understanding important processes involved in fruit development and resistance to viral and fungal pathogens. Also, data presented here provide an important tool for generating markers to saturate melon genetic maps. Discussion In this paper we provide an initial platform for functional genomics of melon by the identification of more than 16,000 unigenes assembled from almost 30,000 ESTs sequenced from 8 melon cDNA libraries. It is probably premature to estimate the proportion of melon genes represented in this dataset, but based on available data for other plant species (i.e. Arabidopsis and rice), it is likely that the melon unigene set characterised here represents approximately between half and one-third of the number of expressed, protein coding genes of melon. Libraries were constructed from various tissue types, but with a bias towards fruit development and pathogen-infected tissues. Data from these libraries will become a useful resource of Potential3precursors of melon microRNAs Figure Potential precursors of melon microRNAs. (A) Stem loop sequence of putative precursor miRNA corresponding to unigene bCI_04-H02-M13R_c. (B) Stem loop sequence of putative precursor miRNA corresponding to unigene b15d_24-H05-M13R_c. The mature miRNA sequences are shown in bold. In contrast to typical EST gene-sampling strategies reported previously, we have found a low degree of redundancy in the sequences determined. The process of clustering reduced the number of sequences to 56%, from 29,604 good quality ESTs to 6,023 contigs and 10,614 singletons. Contigs with more than 8 ESTs were scarce, the majority of them being formed by 3 or 2 ESTs. Redundancy of the sequences derived from each library ranged from 13% to 20%, with singletons constituting approximately one third of the unigenes determined per library. This low redundancy is probably due to the success of the normalization process, responsible for the suppression of superabundant transcripts specific for a given tissue or condition. Normalization precludes in silico analysis of gene expression, but greatly increases the number of unigenes that can be determined by reducing redundancy [76]. Here we have used a recently described normalization protocol which is based on the cleavage of DNA or DNA-RNA duplexes by a specific DNase [77]; this process, in our hands, has proven simple, reproducible and efficient. Another factor that has contributed to the low redundancy values obtained has been the sequencing of libraries from very distinct tissues. Thus, the number of library specific unigenes was about one half of the total number of unigenes contributed by each library, suggesting that further sequencing of the libraries still has the potential to provide a good number of new, non-redundant sequences. cDNA sequences are a useful source of SSRs, which are excellent molecular markers due to their high degree of polymorphism. A common feature of cDNA sequences obtained from plants is the high frequency of SSRs that they contain [36]. We have identified more than 1,000 potential SSRs in the melon dataset, with approximately HIGm O (2)m Table 9: Transcripts selected from the database for gene expression analysis by Real Time qPCR Gene Melogen unigene Sequence length (bp) Arabidopsis locus Aminoacid similarity (%) Annotation (HMMR domain) CTL1 CYP 7 EIF4A-2 EIF4E EIN4 GA2OX1 HSP101 HSP70 IAA9 bCL1465Contig1 1,387 AT1G05850 66.8 bCL3337Contig1 bCL2906Contig1 bCL4710Contig1 bCL1742Contig1 bCL1313Contig1 bCI_38-F11-M13R_c bPSI_41-D06-M13R_c bCL1341Contig1 801 1,146 815 829 1,454 726 819 1,672 AT5G58710 AT1G54270 AT4G18040 AT3G04580 AT1G78440 AT1G74310 AT5G09590 AT5G65670 78.4 92.6 77.5 55.7 59.9 73.4 86.8 51.2 LSM1 bHS_37-F11-M13R_c 766 AT3G14080 72.4 LUT2 NCBP SVP bCL3563Contig1 bCL183Contig1 bCL2852Contig1 1,082 1,081 826 AT5G57030 AT5G18110 AT2G22540 75.5 85.3 54.9 Chitinase-like protein 1, similar to class I chitinase (Glyco_hydro_19) Peptidyl-prolyl cis-trans isomerase, cyclophilin Eukaryotic translation initiation factor 4A-2 (DEAD) Eukaryotic translation initiation factor 4E 1 (IF4E) Ethylene receptor (Response_reg) Gibberellin 2-oxidase (2OG-FeII_Oxy) Heat shock protein 101 (AAA_2) Heat shock protein 70/HSC70-5 (HSP70) Auxin-responsive protein/indoleacetic acid- induced protein 9 (AUX_IAA) Small nuclear ribonucleoprotein/snRNP, putative/Sm protein, putative, similar to U6 snRNA-associated Sm-like protein Lycopene epsilon cyclase (Lycopene_cycl) Novel cap-binding protein (IF4E) Short vegetative phase protein, MADS box transcription factor related cluster (SRF-TF) Band 7 family protein, strong similarity to hypersensitive-induced response protein (Band_7) Xyloglucan:xyloglucosyl transferase/xyloglucan endotransglycosylase/endo- xyloglucan transferase/ TCH4 Tonoplast intrinsic protein (MIP) Transmembrane protein-related/TOM1 (DUF1084) Senescence-associated family protein Tobamovirus multiplication protein 3/THH1 (DUF1084) UDP-glucose 4-epimerase/UDP-galactose 4epimerase/Galactowaldenase (Epimerase) WRKY family transcription factor, DNA-binding protein (WRKY) HIR bCL144Contig1 1,266 AT1G69840 89.7 TCH4 bCL1212Contig1 1,228 AT5G57560 65.9 TIP4 TOM1 TOM2A TOM3 bA_23-B12-M13R_c bCL4416Contig1 bCL3115Contig1 bPSI_36-E03-M13R_c 751 780 1,113 857 AT2G25810 AT4G21790 AT1G32400 AT1G14530 50.5 75.4 60.1 UGE5 bCL1153Contig1 1,313 AT4G10960 70.9 WRKY70 bA_25-B01-M13R_c 889 AT3G56400 42.1 6% of the melon unigenes containing di-, tri- or tetranucleotide repeats. A clear bias toward AG and AAG repeats existed, that account for 67% of the SSRs. In contrast, the GC repeat was not found in the melon dataset. A similar bias toward AG and against CG repeats has been identified in Arabidopsis and other plant species [40,78]. As proposed at least in one other instance [40], this may be due to the tendency of CpG sequences to be methylated [79], which potentially might inhibit transcription. Another interesting feature of melon SSRs relates to their pattern of localization with respect to putative initiation and termination codons. It is known that the UTRs of transcribed sequences are richer in SSRs than coding regions, particularly at the 5'-UTRs [36,40]. However, in the melon dataset, a high proportion of SSRs (29.5%) were found in ORFs. An analysis of the localization of di, tri- and tetranucleotide repeats separately showed that di- and tetranucleotides were preferentially located in UTRs, whereas trinucleotides localised in both, UTRs and ORFs, consistently with maintenance of the ORFs coding capacity. Thus, the prevalence of trinucleotide repeats in the melon dataset (71%) explains this result. We identified in the melon sequence dataset 356 highquality SNPs. Since non-redundant sequences analysed here encompassed 4.5 Mb, one SNP was found every 12,000 pb of sequence. This small figure is probably due to the limited number of melon genotypes used and the low redundancy found among libraries. In fact, when the frequency of SNPs is computed in relation to the length and number of contigs containing SNPs, the corresponding value (one SNP in every 616 bp of sequence) is of the same order of magnitude as values previously calculated for melon (441 bp; [80]) and other plant species [40]. With the advent of high-throughput detection systems, the SSRs and SNPs identified here will constitute an important resource for mapping and marker-assisted breeding in melon and closely related crops. As an approach to the function of melon unigenes, we carried out a bioinformatics analysis based on BLASTX and matches with the Pfam database [49]. The proportion of melon unigenes with no similar sequences in databases was quite high, suggesting that the melon dataset may encompass an important number of melon-specific HIHm (2)O m ! ! ! ! Figure 4 analyzed by Real Time qPCR Transcripts Transcripts analyzed by Real Time qPCR. (A) Pattern of transcripts accumulation in CMV-infected melon cotyledons (CI) relative to that of healthy cotyledons (CS). (B) Pattern of transcripts accumulation in M. cannonballus infected roots of C. melo L. cv. "Piel de sapo" (PSI) relative to that of healthy roots (PS). (C) Pattern of transcripts accumulation in M. cannonballus infected roots of C. melo L. ssp. agrestis (AI) relative to that of healthy roots (A). (D) Pattern of transcripts accumulation in fruits of 15 days after pollination of C. melo L. cv. "Piel de sapo" (15d) relative to that of fruits of 46 days after pollination (46d). cy: cyclophilin endogenous control; see Table 9 for the rest of genes. HIIm O (2)m sequences. However, the proportion specific sequences might be overestimated because blasting has been made with unigene sequences, which in many cases do not cover the complete length of the transcript. We performed a functional classification of the unigenes following the Gene Ontology scheme, which is one of the more versatile and complete systems for functional classification [48]. A comparison of the distributions of melon and Arabidopsis unigenes in GO categories showed that both followed similar tendencies, suggesting that the melon dataset is representative of the whole melon transcriptome. This is remarkable, as the number of different libraries sequenced has been relatively small; again, this is probably due to the success of the normalization process. We have also carried out specific searches for genes involved in pathways of particular relevance in melon, such are resistance response and fruit development, identifying a remarkable number of melon candidates. For example, an ortholog of the flagellin receptor FLS2 from Arabidopsis [62] has been identified, together with 163 candidate RLKs that may have critical roles in pathogen recognition or diverse signalling processes. Similarly, up to 8 MADSbox gene homologs with potential roles in development have been found in the melon dataset. Moreover, a bioinformatics approach [52,53] allowed the identification of potential precursors of melon miRNAs together with several potential targets in the melon dataset. This finding opens the door to biotechnology approaches based on the use of artificial miRNAs to specifically silence melon genes [81,82]. The transcript accumulation analysis for the 20 selected genes revealed important changes in gene expression associated with pathogen infection and fruit development. For virus infection, the accumulation of transcripts remained unaltered for 12 genes, but showed a significant increase for 6 genes and a decrease for 2. Among the set of genes analysed, TOM2A and EIF4E were known to code for virus susceptibility factors [27,83]; the expression of TOM2A was increased after CMV infection, consistently with its requirement by the virus, but this was not the case for EIF4E. Different hypotheses can explain this result: since EIF4E is an abundant, housekeeping protein, increased expression may not be essential for virus multiplication; alternatively, CMV may not use EIF4E in melon or may use a factor coded by a different member of the 4E family; it may also be that timing of the sampling for this experiment was not appropriate to detect such an effect, as requirement of EIF4E might occur very early during virus multiplication. In the cases of infection of susceptible ("Piel de sapo") and resistant (pat81) melons by M. cannonballus, more extensive alterations in gene expression seemed to occur in the susceptible than in the resistant accession. Significantly, for the susceptible accession, stress responsive genes (e.g. HSP101) appeared to be max- imally induced, whereas for the resistant accession, a gene encoding a WRKY70 transcription factor, potentially involved in resistance response, was induced to high levels. Significantly, expression of GA2OX1 increased about 1.5 times in pat81 after the M. cannonballus attack, whereas it decreased in "Piel de sapo". GA2ox is a major gibberellin (GA) catabolic enzyme, with an important role in controlling GA levels in plants. Hormones control many plant developmental processes, and strong evidence indicates that hormone signalling is involved in the regulation of root growth and architecture [84,85]. The differential response of the GA2OX1 gene in the two melon genotypes is consistent with an enhanced root growth in pat81 after infection [86]. Notably, other genes involved in hormone-mediated signalling pathways, such as the IAA9 gene, did not show such differential response to M. cannonballus infection in both genotypes. In the case of fruit development, differences in the expression of selected genes between immature and ripening fruits appeared to be even sharper than in the cases of healthy and pathogen-infected tissues. Specific roles during fruit development for HSP70, TOM2A and TOM3 have not been identified, though an increased expression has been shown at least in the case of TOM2A in tomato [87]. The ethylene receptor gene EIN4 showed a two-fold increase in expression. EIN4 is the ortholog of Arabidopsis EIN4 and tomato LeETR4 [88,89]. In tomato, LeETR4 is also highly expressed in ripening fruit, suggesting that it responds by modulating ethylene signalling during ripening [63]. The MADS-box gene (SVP) showed about a fourfold decrease in expression. This gene is the ortholog of tomato JOINTLESS, which specifies the abscission zone in tomato. In tomato fruit microarray hybridizations, the expression of JOINTLESS also decreased from 7 to 57 DAP [87], in agreement with our data for melon. The lycopene epsilon cyclase (LUT2) and xyloglucan endotransglycosylase (TCH4) genes showed an approximately four-fold decrease in expression during melon fruit development. These findings fit with the patterns of expression of these genes in tomato, where their transcript levels decrease to a non-detectable level in the ripe fruits [90,91]. Conclusion In summary, this collection of ESTs represents a substantial increase on the information available for melon. The dataset contains SSR and SNP markers that can be used for breeding, as well as a significant number of candidate genes that can be experimentally tested for their roles in various important processes. This set of genes constitutes also the basis for a microarray for melon that is being used in experiments to further analyse fruit development and maturation and responses to pathogen infections. HIJm (2)O m Methods Plant material The cDNA libraries were prepared using material from four different melon genotypes: the line T-111 (Semillas Fitó, Barcelona, Spain), which corresponds to a Piel de Sapo breeding line, the Piel de Sapo cultivar "Piñonet torpedo" (Semillas Batlle, Barcelona, Spain), the accession C35 of the germplasm collection of La Mayora-CSIC (EELM-CSIC, Málaga, Spain), which corresponds to a cantaloupe-type of melon, and the accession pat81 of C. melo L. ssp. agrestis (Naud.) Pangalo maintained at the germplasm bank of COMAV (COMAV-UPV, Valencia, Spain) (Table 1). Seeds of line T-111 were germinated at 30°C for two days and plants were grown in a greenhouse in peat bags, drip irrigated, with 0.25-m spacing between plants. Fruits of 15 and 46 days after pollination were collected and mesocarp tissues were recovered and used for RNA extractions. Root samples were from Piel de sapo and pat81 plants, both healthy and inoculated with M. cannonballus. Piel de sapo is fully susceptible to the infection by this fungus whereas pat81 has been shown to be partially resistant [92,93]. Seeds were pre-germinated in Petri dishes. After 4 days, seedlings were transplanted to 0.5-l pots filled with sterile soil substrate and grown in a greenhouse (20–35°C, 60–85% relative humidity). Inoculations were carried out by adding 50 colony-forming units (CFU) of M. cannonballus per gram of sterile soil as described by Iglesias et al. [94]. Fourteen days after inoculation, healthy and inoculated roots were collected for RNA extraction. The presence of the fungus and the infection levels were assessed by real-time quantitative PCR as described by Picó et al. [95]. CMV infected cotyledons were collected from plants of the C-35 accession. In this case, seeds were pregerminated in Petri dishes for 24 h at 28°C in the dark, planted in 0.5-l pots and maintained in an insect-proof green house (20–28°C, 45 to 85% relative humidity) for 6 to 7 days, until the first true leaf started emerging. At this stage, cotyledons were mechanically inoculated with CMV following standard procedures [96]. Inoculated cotyledons were harvested 4 days after inoculation and used for RNA extractions. Dot-blot hybridisation [97] was used to check infection by CMV. Plants of the C-35 accession were also used for collecting healthy leaves. Plants were maintained in the greenhouse for 21 days, and second and third leaves above cotyledons were harvested for RNA extractions. Construction of cDNA libraries and EST sequencing Total RNA was prepared as described by Aranda et al. [98]. Poly(A+) RNA from total RNA was purified using MicroPoly(A+) Purist (Ambion, Austin, TX, USA), a celluloseoligo(dT)-based method. Integrity and quality of both total and poly(A+) RNA were tested by gel electrophoresis. cDNA libraries were constructed with the SMART cDNA Library Construction kit (Clontech, Mountain View, CA, USA), using a modified primer to include a Sfi I enzyme restriction site. A normalization step was carried out with TRIMMER kit (Evrogen, Moscow, Russia). After normalization, a cDNA fractionation step was performed with SizeSep 400 Spun Columns (Amersham Biosciences, Buckinghamshire, England). cDNA was digested with Sfi I, generating Sfi IA-Sfi IB cohesive ends for directional cloning into a modified version of BlueScript SK plasmid vector (Stratagene, La Jolla, CA, USA). Ligation products were transformed into E. coli electrocompetent cells DH10B (Invitrogen, Carlsbad, CA, USA) by electroporation. The titer of the libraries was evaluated by plating an aliquot on LB agar plates with ampicillin at 100 g ml-1. Only libraries of 105 cfu ml-1 or more were considered as acceptable. Prior to large scale sequencing, the average insert size was estimated by restriction analyses of 24 plasmid DNA minipreps per library from randomly picked colonies. Sequencing was carried out from the 5'-end of the inserts without library amplification using the universal M13 reverse primer. An external custom service was contracted for this task (Macrogen Inc., Seoul, Korea). Approximately 6,000 clones were sequenced from the CI library, and 3,500 clones were sequenced from each of the other libraries (Table 2). Sequences obtained in this work can be found in GenBank [accession numbers AM713476 to AM743079] and MELOGEN [44]. Bioinformatics EST sequences were automatically trimmed, clustered and annotated using the EST2uni analysis pipeline [43]. EST2uni compromises the analysis pipeline written in PERL [99], a database (MySQL) [100] and a web site to browse the results coded in PHP [101]. Thus, for the EST pre-processing step, base calling was performed with Phred [102], low quality regions and vector sequences were trimmed with Lucy [103], and repeats and low complexity regions were masked with RepeatMasker [104] and Seqclean [105]. Further vector contamination was also eliminated with Seqclean using NCBI's UniVec [106]. High-quality EST sequences were then assembled to obtain the unigene set using Tgicl [105]. Detection of SSRs was performed using Sputnik [107]. Putative SNPs were annotated when the least represented allele was present in two EST sequences or more. ORFs were predicted in the ESTs with the aid of the ESTScan software [108]. For functional annotation, comparisons against the Arabidopsis (TAIR) [109] and Uniref [110] databases were carried out using BLASTN or BLASTX for nucleotide or protein sequences, respectively. Functional domains were searched with HMMPFAM [111] using the Pfam database HIKm O (2)m [112]. The Gene Ontology (GO) classification [48] was derived from the BLASTN results against the Arabidopsis proteome. Also, a bi-directional BLASTN comparison was performed in order to obtain a set of putative orthologs with Arabidopsis. Finally, a set of superunigenes was obtained grouping different unigenes with the same expected mRNA target, as judged by extensive sequence overlapping. To assess codon usage, we generated a set of melon sequences predicted to contain full-length coding regions. These sequences were subjected to BLASTX and, after manual inspection, sequences showing a high similarity to Arabidopsis proteins were selected to ensure that no sequences containing frame-shift errors were included in the analysis. From this smaller dataset, which included 588 sequences, ORFs were defined and a codon usage table was created. Codon usage was calculated from sequences using the GCUA program [113]. All codons were found in the dataset, with the least frequent codon represented 134 times. To identify potential melon miRNAs, the 33,292 melon ESTs were subjected to a BLAST search against mature sequences of known miRNAs from the miRNA Registry Database (released January 2007) [54] using BLASTN [47]. ESTs with only 0–1 mismatched nucleotides with known miRNAs were considered. Selected ESTs were subjected to a BLAST search against protein databases in order to remove potential protein-coding sequences. ESTs pertaining to the same melon unigene of the MELOGEN database were grouped. The secondary structures of the unigenes encoding potential miRNA precursors were predicted with the web-based tool MFOLD [55], using default parameters. In each case, only the lower energy structure was selected for visual inspection, as previously described [52,114]. In order to select unigenes with perfect or near-perfect secondary foldback hairpin structures, only sequences with a maximum size of 3 nucleotides for a bulge in the miRNA sequence and with at least 16 paired nucleotides between the mature sequence and the opposite arm were considered as potential miRNA candidates. In addition, the minimal folding free energy index (MFEI) for each sequence was calculated following Zhang et al. [53]. Gene expression analyses Real time quantitative PCR was performed with an AB 7500 System (Applied Biosystems, Foster City, CA, U.S.A) to quantify mRNA corresponding to some transcripts of interest, in the tissues and physiological conditions used for library construction. Twenty ESTs representing these transcripts were chosen from the database and used to generate gene-specific primers (Table 10) with Primer Express Software (Applied Biosystems). The chemistry used for PCR product detection was the Power SYBR green dye (Applied Biosystems) and ROX as passive reference. CYCLOPHILIN served as endogenous control (sequence extracted from the database), Ct was the method of calculation to perform relative quantification, and three technical replicates were carried out and considered for statistical analysis. Melting curves analyses at the end of Table 10: Primer sequences for Real Time-qPCR analysis of transcript accumulation Gene Primer sequence (5'->3') Forward Reverse CTL1 CYP 7 EIF4A-2 EIF4E EIN4 GA2OX1 HSP101 HSP70 IAA9 LSM1 LUT2 NCBP SVP HIR TCH4 TIP4 TOM1 TOM2A TOM3 UGE5 WRKY70 tgggccatgttggctctaag cgatgtggaaattgacggaa ttcccgaggtttcaaagatca ttcggttccttcccttccat tgcaacgtgactgctgtttct tagggcaaatcggttagcga aacgtatggtgcggattgaca gctgaggcgtaccttggaaa gacggaaagccaggttcaag ctacttcgagatgggcggaa gctggcgtggaacactcttt cgtcggtctgcttaatttgca cgaggcaggtcacgttctct tgacgggctcagagacagtg ggagggtagccttgagggaat tccttgctggtgtcggatc gggagaaggaagaaacttcatgag ctcctcagcagccgaagaaa aatggagttcgggctgttgt gcgaaagtgtccaaaagcca ggattgctcctggcctgac ctcccgtgacaactccatca cggtgcataatgctcggaa ccaatgcttctggtggcact ccgccgatgtagctttcatc tctggcatgtgaagatccaaga ccaaatgcaaaccgattgaa tccaccttcatggtatccaacat atcctgccagcatcctttgt cccctccatactcactttcacaa tcaccaacgatcaccctttca cgaatgccttcaatgtccagt cgcctacgaactccattgaca agagaagacgaggagcgcaa gttccagggacgttttcagc ctggacattgctcgacaacaa cgtttgccaataacgcattg gcgtcaaaagcggataaagc tggacccgctaaaacaccac aaggcaaggcttggcatgt acacaagctttttgcatccgt tcggctgcttttcttcgatc HILm (2)O m the process and No Template Controls (NTC) were carried out to ensure product-specific amplification and no primer-dimer quantification. A control reaction as for reverse transcription but without the enzyme was performed to evaluate genomic DNA contamination. !!! 4. 5. 6. Authors' contributions Daniel Gonzalez-Ibeas prepared RNAs for two libraries, constructed the eight libraries, carried out the gene expression analysis by Real-Time-qPCR and participated in the bioinformatics analyses and in the drafting of the manuscript. José Blanca carried out the bioinformatics analyses, EST database and web page, and participated in the drafting of the manuscript. Cristina Roig and Belén Picó prepared RNAs for the root libraries and participated in the drafting of the manuscript. Mireia González-To, Wim Deleu and Jordi Garcia-Mas prepared RNAs from melon fruits and participated in the drafting of the manuscript. Pere Puigdomènech is the main coordinator of The MELOGEN Project and participated in the conception of the study together with Pere Arús, Fernando Nuez, Jordi Garcia-Mas and Miguel A. Aranda. Miguel A. Aranda is the principal investigator or this work, supervised it and wrote the manuscript. All authors read and approved the final manuscript. Additional material 7. 8. 9. 10. 11. 12. 13. 14. Additional file 1 Genes potentially encoding pathogen resistance and fruit quality traits. Genes were identified in the melon data set by comparison with the Arabidopsis database [6,109]. A brief description, the corresponding Arabidopsis locus and the HMMR domain identified are given for each unigene. Click here for file [http://www.biomedcentral.com/content/supplementary/14712164-8-306-S1.pdf] 15. 16. 17. 18. 19. Acknowledgements This work was supported by grants from Ministerio de Educación y Ciencia (Spain) (GEN2003-20237-C06) and Consejería de Educación y Cultura (Región de Murcia, Spain) (BIO2005/04-6436). Wim Deleu, Cristina Roig and Daniel Gonzalez-Ibeas are recipient of a postdoctoral fellowship from the Centre de Recerca en Agrigenòmica CSIC-IRTA (Spain), a Juan de la Cierva grant from Ministerio de Educación y Ciencia (Spain) and a predoctoral fellowship from Ministerio de Educación y Ciencia (Spain), respectively. 20. 21. 22. References 1. 2. 3. FAOSTAT Agriculture data [http://faostat.fao.org/default.aspx] Jayasooriya AP, Sakono M, Yukizaki C, Kawano M, Yamamoto K, Fukuda N: Effects of Momordica charantia powder on serum glucose levels and various lipid parameters in rats fed with cholesterol-free and cholesterol-enriched diets. J Ethnopharmacol 2000, 72:331-336. Arumuganathan K, Earle ED: Nuclear DNA content of some important plant species. Plant Mol Biol Rep 1991, 9:208-218. 23. 24. Goff SA, Ricke D, Lan TH, Presting G, Wang R, Dunn M, Glazebrook J, Sessions A, Oeller P, Varma H, others: A Draft Sequence of the Rice Genome (Oryza sativa L. ssp. japonica). Science 2002, 296:92-100. Yu J, Hu S, Wang J, Wong GK-S, Li S, Liu B, Deng Y, Dai L, Zhou Y, Zhang X, others: A Draft Sequence of the Rice Genome (Oryza sativa L. ssp. indica). Science 2002, 296:79-92. Arabidopsis Genome Initiative: The Arabidopsis Information Resource (TAIR): a comprehensive database and web-based information retrieval, analysis, and visualization system for a model plant. Nucleic Acids Res 2001, 29:102-105. Kirkbride JH: Biosystematic monograph of the genus Cucumis (Cucurbitaceae) Boone, North Carolina: Parkway Publishers; 1993. Garcia-Mas J, Monforte AJ, Arus P: Phylogenetic relationships among Cucumis species based on the ribosomal internal transcribed spacer sequence and microsatellite markers. Plant Syst Evol 2004, 248:191-203. Liu L, Kakihara F, Kato M: Characterization of six varieties of Cucumis melo L. based on morphological and physiological characters, including shelf-life of fruit. Euphytica 2004, 135:305-313. Miccolis V, Saltveit ME: Morphological and physiological changes during fruit growth and maturation of seven melon cultivars. J Am Soc Hort Sci 1991, 116:1025-1029. Shalit M, Katzir N, Tadmor Y, Larkov O, Burger Y, Shalekhet F, Lastochkin E, Ravid U, Amar O, Edelstein M, others: Acetyl-CoA: Alcohol acetyltransferase activity and aroma formation in ripening melon fruits. J Agric Food Chem 2001, 49:794-799. Bauchot AD, Mottram DS, Dodson AT, John P: Effect of Aminocyclopropane-1-carboxylic Acid Oxidase Antisense Gene on the Formation of Volatile Esters in Cantaloupe Charentais Melon (Cv. Védrandais). J Agric Food Chem 1998, 46:4787-4792. Flores F, El Yahyaoui F, de Billerbeck G, Romojaro F, Latche A, Bouzayen M, Pech JC, Ambid C: Role of ethylene in the biosynthetic pathway of aliphatic ester aroma volatiles in Charentais Cantaloupe melons. J Exp Bot 2002, 53:201-206. Yahyaoui FEL, Wongs-Aree C, Latche A, Hackett R, Grierson D, Pech JC: Molecular and biochemical characteristics of a gene encoding an alcohol acyl-transferase involved in the generation of aroma volatile esters during melon ripening. FEBS J 2002, 269:2359-2366. Hadfield KA, Bennett AB: Polygalacturonases: Many Genes in Search of a Function. Plant Physiol 1998, 117:337-343. Rose JKC, Hadfield KA, Labavitch JM, Bennett AB: Temporal sequence of cell wall disassembly in rapidly ripening melon fruit. Plant Physiol 1998, 117:345-361. Bennett AB: Biochemical and genetic determinants of cell wall disassembly in ripening fruit: A general model. Hortscience 2002, 37:447-450. Haritatos E, Keller F, Turgeon R: Raffinose oligosaccharide concentrations measured in individual cell and tissue types in Cucumis melo L leaves: Implications for phloem loading. Planta 1996, 198:614-622. Volk GM, Turgeon R, Beebe DU: Secondary plasmodesmata formation in the minor-vein phloem of Cucumis melo L and Cucurbita pepo L. Planta 1996, 199:425-432. Gomez G, Torres H, Pallas V: Identification of translocatable RNA-binding phloem proteins from melon, potential components of the long-distance RNA transport system. Plant J 2005, 41:107-116. Chen JQ, Rahbé Y, Delobel B, Sauvion N, Guillaud J, Febvay G: resistance to the aphid Aphis gossypii: behavioural analysis and chemical correlations with nitrogenous compounds. Entomol Exp Appl 1997, V85:33-44. Luo MZ, Wang YH, Frisch D, Joobeur T, Wing RA, Dean RA: Melon bacterial artificial chromosome (BAC) library construction using improved methods and identification of clones linked to the locus conferring resistance to melon Fusarium wilt (Fom-2). Genome 2001, 44:154-162. Klingler J, Powell G, Thompson GA, Isaacs R: Phloem specific aphid resistance in Cucumis melo line AR 5: effects on feeding behaviour and performance of Aphis gossypii. Entomol Exp Appl 1998, 86:79-88. Marco CF, Aguilar JM, Abad J, Gomez-Guillamon ML, Aranda MA: Melon resistance to Cucurbit yellow stunting disorder virus HIMm O (2)m 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. is characterized by reduced virus accumulation. Phytopathology 2003, 93:844-852. Diaz JA, Nieto C, Moriones E, Truniger V, Aranda MA: Molecular characterization of a Melon necrotic spot virus strain that overcomes the resistance in melon and nonhost plants. Mol Plant-Microbe Interact 2004, 17:668-675. Klingler J, Creasy R, Gao LL, Nair RM, Calix AS, Jacob HS, Edwards OR, Singh KB: Aphid resistance in Medicago truncatula involves antixenosis and phloem-specific, inducible antibiosis, and maps to a single locus flanked by NBS-LRR resistance gene analogs. Plant Physiol 2005, 137:1445-1455. Nieto C, Morales M, Orjeda G, Clepet C, Monfort A, Sturbois B, Puigdomenech P, Pitrat M, Caboche M, Dogimont C, others: An eIF4E allele confers resistance to an uncapped and non-polyadenylated RNA virus in melon. Plant J 2006, 48:452-462. Perin C, Hagen L, Conto VD, Katzir N, Danin-Poleg Y, Portnoy V, Baudracco-Arnas S, Chadoeuf J, Dogimont C, Pitrat M: A reference map of Cucumis melo based on two recombinant inbred line populations. Theor Appl Genet 2002, 104:1017-1034. Gonzalo MJ, Oliver M, Garcia-Mas J, Monfort A, Dolcet-Sanjuan R, Katzir N, Arus P, Monforte A: Simple-sequence repeat markers used in merging linkage maps of melon (Cucumis melo L.). Theor Appl Genet 2005, 110:802-811. Eduardo I, Arus P, Monforte AJ: Development of a genomic library of near isogenic lines (NILs) in melon (Cucumis melo L.) from the exotic accession PI161375. Theor Appl Genet 2005, 112:139-148. Ayub R, Guis M, BenAmor M, Gillot L, Roustan JP, Latche A, Bouzayen M, Pech JC: Expression of ACC oxidase antisense gene inhibits ripening of cantaloupe melon fruits. Nat Biotechnol 1996, 14:862-866. Guis M, Roustan JP, Dogimont C, Pitrat M, Pech JC: Melon biotechnology. Biotechnol Genet Engng Rev 1998, 15:289-311. Gaba V, Zelcer A, Gal-On A: Cucurbit biotechnology – The importance of virus resistance. In Vitro Cell Dev Biol Plant 2004, 40:346-358. Rudd S: Expressed sequence tags: alternative or complement to whole genome sequences? Trends Plant Sci 2003, 8:321-329. Alba R, Fei Z, Payton P, Liu Y, Moore SL, Debbie P, Cohn J, D'Ascenzo M, Gordon JS, Rose JKC, others: ESTs, cDNA microarrays, and gene expression profiling: tools for dissecting plant physiology and development. Plant J 2004, 39:697-714. Morgante M, Hanafey M, Powell W: Microsatellites are preferentially associated with nonrepetitive DNA in plant genomes. Nat Genet 2002, 30:194-200. Rafalski JA: Novel genetic mapping tools in plants: SNPs and LD-based approaches. Plant Sci 2002, 162:329-333. Ouyang S, Zhu W, Hamilton J, Lin H, Campbell M, Childs K, ThibaudNissen F, Malek RL, Lee Y, Zheng L, others: The TIGR Rice Genome Annotation Resource: improvements and new features. Nucleic Acids Res 2007, 35:D883-D887. Fei ZJ, Tang XM, Alba R, Giovannoni J: Tomato Expression Database (TED): a suite of data presentation and analysis tools. Nucleic Acids Res 2006, 34:D766-D770. Newcomb RD, Crowhurst RN, Gleave AP, Rikkerink EHA, Allan AC, Beuning LL, Bowen JH, Gera E, Jamieson KR, Janssen BJ, others: Analyses of expressed sequence tags from apple. Plant Physiol 2006, 141:147-166. Goes da Silva F, Iandolino A, Al Kayal F, Bohlmann MC, Cushman MA, Lim H, Ergul A, Figueroa R, Kabuloglu EK, Osborne C, others: Characterizing the Grape Transcriptome. Analysis of Expressed Sequence Tags from Multiple Vitis Species and Development of a Compendium of Gene Expression during Berry Development. Plant Physiol 2005, 139:574-597. Forment J, Gadea J, Huerta L, Abizanda L, Agusti J, Alamar S, Alos E, Andres F, Arribas R, Beltran JP, others: Development of a citrus genome-wide EST collection and cDNA microarray as resources for genomic studies. Plant Mol Biol 2005, 57:375-391. EST2uni [http://www.melogen.upv.es/genomica/web_estpipe/ index.php] MELOGEN database [http://www.melogen.upv.es] Sterky F, Bhalerao RR, Unneberg P, Segerman B, Nilsson P, Brunner AM, Charbonnel-Campaa L, Lindvall JJ, Tandre K, Strauss SH, others: A Populus EST resource for plant functional genomics. Proc Natl Acad Sci USA 2004, 101:13951-13956. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. Hsiang T, Goodwin PH: Distinguishing plant and fungal sequences in ESTs from infected plant tissues. J Microbiol Methods 2003, 54:339-351. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25:3389-3402. The Gene Ontology Consortium: Gene Ontology: tool for the unification of biology. Nat Genet 2000, 25:25-29. Finn RD, Mistry J, Schuster-Bockler B, Griffiths-Jones S, Hollich V, Lassmann T, Moxon S, Marshall M, Khanna A, Durbin R, others: Pfam: clans, web tools and services. Nucleic Acids Res 2006, 34:D247-D251. Carrington JC, Ambros V: Role of microRNAs in plant and animal development. Science 2003, 301:336-338. Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116:281-297. Zhang BH, Pan XP, Cannon CH, Cobb GP, Anderson TA: Conservation and divergence of plant microRNA genes. Plant J 2006, 46:243-259. Zhang BH, Pan XP, Cox SB, Cobb GP, Anderson TA: Evidence that miRNAs are different from other RNAs. Cell Mol Life Sci 2006, 63:246-254. Griffiths-Jones S: The microRNA Registry. Nucleic Acids Res 2004, 32:D109-D111. Zuker M: Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 2003, 31:3406-3415. Palatnik JF, Allen E, Wu XL, Schommer C, Schwab R, Carrington JC, Weigel D: Control of leaf morphogenesis by microRNAs. Nature 2003, 425:257-263. Gustafson AM, Allen E, Givan S, Smith D, Carrington JC, Kasschau KD: ASRP: the Arabidopsis Small RNA Project Database. Nucleic Acids Res 2005, 33:D637-D640. Chisholm ST, Coaker G, Day B, Staskawicz BJ: Host-microbe interactions: Shaping the evolution of the plant immune response. Cell 2006, 124:803-814. Kushner DB, Lindenbach BD, Grdzelishvili VZ, Noueiry AO, Paul SM, Ahlquist P: Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus. Proc Natl Acad Sci USA 2003, 100:15764-15769. Diaz-Pendon JA, Truniger V, Nieto C, Garcia-Mas J, Bendahmane A, Aranda MA: Advances in understanding recessive resistance to plant viruses. Mol Plant Pathol 2004, 5:223-233. Robaglia C, Caranta C: Translation initiation factors: a weak link in plant RNA virus infection. Trends Plant Sci 2006, 11:40-45. Gomez-Gomez L, Boller T: FLS2: An LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol Cell 2000, 5:1003-1011. Giovannoni JJ: Genetic regulation of fruit development and ripening. Plant Cell 2004, 16:S170-S180. Tanksley SD: The genetic, developmental, and molecular bases of fruit size and shape variation in tomato. Plant Cell 2004, 16:S181-S189. Pinyopich A, Ditta GS, Savidge B, Liljegren SJ, Baumann E, Wisman E, Yanofsky MF: Assessing the redundancy of MADS-box genes during carpel and ovule development. Nature 2003, 424:85-88. Dinneny JR, Weigel D, Yanofsky MF: A genetic framework for fruit patterning in Arabidopsis thaliana. Development 2005, 132:4687-4696. Pitrat M: 2002 gene list for melon. Cucurbit Genet Coop Rep 2002, 25:76-93. Monforte AJ, Oliver M, Gonzalo MJ, Alvarez JM, Dolcet-Sanjuan R, Arus P: Identification of quantitative trait loci involved in fruit quality traits in melon (Cucumis melo L.). Theor Appl Genet 2004, 108:750-758. Frary A, Nesbitt TC, Frary A, Grandillo S, van der Knaap E, Cong B, Liu JP, Meller J, Elber R, Alpert KB, others: fw2.2: A quantitative trait locus key to the evolution of tomato fruit size. Science 2000, 289:85-88. Liu JP, Van Eck J, Cong B, Tanksley SD: A new class of regulatory genes underlying the cause of pear-shaped tomato fruit. Proc Natl Acad Sci USA 2002, 99:13302-13306. Manning K, Tor M, Poole M, Hong Y, Thompson AJ, King GJ, Giovannoni JJ, Seymour GB: A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening. Nat Genet 2006, 38:948-952. HINm (2)O m 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. Aranda MA, Escaler M, Wang D, Maule AJ: Induction of HSP70 and polyubiquitin expression associated with plant virus replication. Proc Natl Acad Sci USA 1996, 93:15289-15293. Escaler M, Aranda MA, Roberts IM, Thomas CL, Maule AJ: A comparison between virus replication and abiotic stress (heat) as modifiers of host gene expression in pea. Mol Plant Pathol 2000, 1:159-167. Whitham SA, Yang CL, Goodin MM: Global impact: Elucidating plant responses to viral infection. Mol Plant-Microbe Interact 2006, 19:1207-1215. Aranda M, Maule A: Virus-induced host gene shutoff in animals and plants. Virology 1998, 243:261-267. Bonaldo MDF, Lennon G, Soares MB: Normalization and subtraction: Two approaches to facilitate gene discovery. Genome Res 1996, 6:791-806. Zhulidov PA, Bogdanova EA, Shcheglov AS, Vagner LL, Khaspekov GL, Kozhemyako VB, Matz MV, Meleshkevitch E, Moroz LL, Lukyanov SA, others: Simple cDNA normalization using kamchatka crab duplex-specific nuclease. Nucleic Acids Res 2004, 32:e37. Zhang LD, Yuan DJ, Yu SW, Li ZG, Cao YF, Miao ZQ, Qian HM, Tang KX: Preference of simple sequence repeats in coding and non-coding regions of Arabidopsis thaliana. Bioinformatics 2004, 20:1081-1086. Finnegan EJ, Genger RK, Peacock WJ, Dennis ES: DNA methylation in plants. Annu Rev Plant Physiol Plant Mol Biol 1998, 49:223-247. Morales M, Roig E, Monforte AJ, Arus P, Garcia-Mas J: Singlenucleotide polymorphisms detected in expressed sequence tags of melon (Cucumis melo L.). Genome 2004, 47:352-360. Niu QW, Lin SS, Reyes JL, Chen KC, Wu HW, Yeh SD, Chua NH: Expression of artificial microRNAs in transgenic Arabidopsis thaliana confers virus resistance. Nat Biotechnol 2006, 24:1420-1428. Schwab R, Ossowski S, Riester M, Warthmann N, Weigel D: Highly specific gene silencing by artificial microRNAs in Arabidopsis. Plant Cell 2006, 18:1121-1133. Yamanaka T, Imai T, Satoh R, Kawashima A, Takahashi M, Tomita K, Kubota K, Meshi T, Naito S, Ishikawa M: Complete inhibition of tobamovirus multiplication by simultaneous mutations in two homologous host genes. J Virol 2002, 76:2491-2497. Malamy JE: Intrinsic and environmental response pathways that regulate root system architecture. Plant Cell Environ 2005, 28:67-77. Radi A, Dina P, Guy A: Expression of sarcotoxin IA gene via a root-specific tob promoter enhanced host resistance against parasitic weeds in tomato plants. Plant Cell Rep 2006, 25:297-303. Dias RDS, Pico B, Espinos A, Nuez F: Resistance to melon vine decline derived from Cucumis melo ssp agrestis: genetic analysis of root structure and root response. Plant Breeding 2004, 123:66-72. Tomato expression database [http://ted.bti.cornell.edu] Sakai H, Hua J, Chen QHG, Chang CR, Medrano LJ, Bleecker AB, Meyerowitz EM: ETR2 is an ETR1-like gene involved in ethylene signaling in Arabidopsis. Proc Natl Acad Sci USA 1998, 95:5812-5817. Tieman DM, Klee HJ: Differential expression of two novel members of the tomato ethylene-receptor family. Plant Physiol 1999, 120:165-172. Ronen G, Cohen M, Zamir D, Hirschberg J: Regulation of carotenoid biosynthesis during tomato fruit development: Expression of the gene for lycopene epsilon-cyclase is downregulated during ripening and is elevated in the mutant Delta. Plant J 1999, 17:341-351. Catala C, Rose JKC, Bennett AB: Auxin-regulated genes encoding cell wall-modifying proteins are expressed during early tomato fruit growth. Plant Physiol 2000, 122:527-534. Esteva J, Nuez F: Field resistance to melon dieback in Cucumis melo L. Cucurbit Genet Coop 1994, 17:76-77. Iglesias A, Pico B, Nuez F: A temporal genetic analysis of disease resistance genes: resistance to melon vine decline derived from Cucumis melo var. agrestis. Plant Breeding 2000, 119:329-334. Iglesias A, Picó B, Nuez F: Artificial inoculation methods and selection criteria for breeding melons against vine decline. Acta Hortic 2000, 510:155-162. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. Picó B, Roig C, Fita A, Nuez F: Detección de Monosporascus cannonballus en raíces de melón mediante PCR cuantitativa en tiempo real. Acta Port Hortic 2005, 7:169-176. Hull S: Matthews's plant Virology San Diego: Academic Press; 2002. Sambrook J, Rusell DW: Molecular cloning A laboratory manual. New York: CSHL PRESS; 2001. Aranda MA, Escaler M, Thomas CL, Maule AJ: A heat shock transcription factor in pea is differentially controlled by heat and virus replication. Plant J 1999, 20:153-161. PERL [http://www.perl.org] MySQL [http://www.mysql.com] PHP [http://www.php.net] Ewing B, Hillier L, Wendl MC, Green P: Base-calling of automated sequencer traces using Phred. I. Accuracy assessment. Genome Res 1998, 8:175-185. Chou HH, Holmes MH: DNA sequence quality trimming and vector removal. Bioinformatics 2001, 17:1093-1104. RepeatMasker [http://www.repeatmasker.org] DFCI Gene Indices Software Tools [http://compbio.dfci.har vard.edu/tgi/software/] NCBI's UniVec [http://www.ncbi.nlm.nih.gov/VecScreen/Uni Vec.html] Sputnik [http://capb.dbi.udel.edu/main/ssr-proj/ssr-file/descrip tion.html] ESTScan software [http://www.isrec.isb-sib.ch/ftp-server/ESTS can/] TAIR: the Arabidopsis information resource [http://www.ara bidopsis.org/] Uniref [http://www.ebi.ac.uk/uniref/] Eddy SR: Profile hidden Markov models. Bioinformatics 1998, 14:755-763. Pfam database [http://www.sanger.ac.uk/Software/Pfam/] McInerney JO: GCUA (General Codon Usage Analysis). Bioinformatics 1998, 14:372-373. Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B, Bartel DP: MicroRNAs in plants. Genes Dev 2002, 16:1616-1626. Apweiler R, Bairoch A, Wu CH, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M, others: UniProt: the Universal Protein knowledgebase. Nucleic Acids Res 2004, 32:D115-D119. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp HIOm O (2)m BMC Plant Biology BioMed Central Open Access Research article A set of EST-SNPs for map saturation and cultivar identification in melon Wim Deleu†1, Cristina Esteras†2, Cristina Roig2, Mireia González-To1, Iria Fernández-Silva1, Daniel Gonzalez-Ibeas3, José Blanca2, Miguel A Aranda3, Pere Arús1, Fernando Nuez2, Antonio J Monforte1,4, Maria Belén Picó2 and Jordi Garcia-Mas*1 Address: 1IRTA, Centre de Recerca en Agrigenòmica CSIC-IRTA-UAB, Carretera de Cabrils Km 2, 08348 Cabrils (Barcelona), Spain, 2COMAV-UPV, Institute for the Conservation and Breeding of Agricultural Biodiversity, Universidad Politécnica de Valencia, Camino de Vera s/n, 46022 Valencia, Spain, 3Departamento de Biología del Estrés y Patología Vegetal, Centro de Edafología y Biología Aplicada del Segura (CEBAS)- CSIC, Apdo. correos 164, 30100 Espinardo (Murcia), Spain and 4Instituto de Biología Molecular y Celular de Plantas (IBMCP) UPV-CSIC, Ciudad Politécnica de la Innovación Edificio 8E, Ingeniero Fausto Elio s/n, 46022 Valencia, Spain Email: Wim Deleu - [email protected]; Cristina Esteras - [email protected]; Cristina Roig - [email protected]; Mireia GonzálezTo - [email protected]; Iria Fernández-Silva - [email protected]; Daniel Gonzalez-Ibeas - [email protected]; José Blanca - [email protected]; Miguel A Aranda - [email protected]; Pere Arús - [email protected]; Fernando Nuez - [email protected]; Antonio J Monforte - [email protected]; Maria Belén Picó - [email protected]; Jordi Garcia-Mas* - [email protected] * Corresponding author †Equal contributors Published: 15 July 2009 BMC Plant Biology 2009, 9:90 doi:10.1186/1471-2229-9-90 Received: 31 March 2009 Accepted: 15 July 2009 This article is available from: http://www.biomedcentral.com/1471-2229/9/90 © 2009 Deleu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: There are few genomic tools available in melon (Cucumis melo L.), a member of the Cucurbitaceae, despite its importance as a crop. Among these tools, genetic maps have been constructed mainly using marker types such as simple sequence repeats (SSR), restriction fragment length polymorphisms (RFLP) and amplified fragment length polymorphisms (AFLP) in different mapping populations. There is a growing need for saturating the genetic map with single nucleotide polymorphisms (SNP), more amenable for high throughput analysis, especially if these markers are located in gene coding regions, to provide functional markers. Expressed sequence tags (ESTs) from melon are available in public databases, and resequencing ESTs or validating SNPs detected in silico are excellent ways to discover SNPs. Results: EST-based SNPs were discovered after resequencing ESTs between the parental lines of the PI 161375 (SC) × 'Piel de sapo' (PS) genetic map or using in silico SNP information from EST databases. In total 200 EST-based SNPs were mapped in the melon genetic map using a bin-mapping strategy, increasing the map density to 2.35 cM/marker. A subset of 45 SNPs was used to study variation in a panel of 48 melon accessions covering a wide range of the genetic diversity of the species. SNP analysis correctly reflected the genetic relationships compared with other marker systems, being able to distinguish all the accessions and cultivars. Conclusion: This is the first example of a genetic map in a cucurbit species that includes a major set of SNP markers discovered using ESTs. The PI 161375 × 'Piel de sapo' melon genetic map has around 700 markers, of which more than 500 are gene-based markers (SNP, RFLP and SSR). This genetic map will be a central tool for the construction of the melon physical map, the step prior to sequencing the complete genome. Using the set of SNP markers, it was possible to define the genetic relationships within a collection of forty-eight melon accessions as efficiently as with SSR markers, and these markers may also be useful for cultivar identification in Occidental melon varieties. Page 1 of 9 (page number not for citation purposes) HJFm (2)O m BMC Plant Biology 2009, 9:90 Background Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation found in DNA [1] and are valuable markers for high-throughput genetic mapping, genetic variation studies and association mapping in crop plants. Several methods have been described for SNP discovery [2]: SNP mining from expressed sequence tag (EST) databases [3]; based on array hybridization [4] or amplicon resequencing [5]; from the complete sequence of a genome [6] and more recently, using high-throughput sequencing technologies [7]. The discovery of SNP markers based on transcribed regions has become a common application in plants because of the large number of ESTs available in databases, and EST-SNPs have been successfully mined from EST databases in non-model species such as Atlantic salmon [8], catfish [9], tomato [10] and white spruce [11]. Melon (Cucumis melo L.) is an important crop worldwide. It belongs to the Cucurbitaceae family, which also includes cucumber, watermelon, pumpkin and squash. The melon genome has an estimated size of 450 Mb [12] and is a diploid with a basic chromosome number of x = 12. In recent years research has been carried out to increase the genetic and genomic resources for this species, such as the sequencing of ESTs [13], the construction of a BAC library [14], the development of an oligo-based microarray [15] and the development of a collection of near isogenic lines (NILs) [16]. Genetic maps have also been reported for melon, but they have been constructed with different types of molecular markers and genetic backgrounds [1721], making it difficult to transfer markers from one map to another. The aim of the International Cucurbit Genomics Initiative (ICuGI) [22], currently in progress, is to obtain a consensus genetic map by merging genetic maps available using a common set of SSRs as anchor markers. A double haploid line (DHL) population from the cross between the Korean accession PI 161375 (SC) and the inodorus type 'Piel de sapo' T111 (PS) was the basis for the construction of a genetic map with 221 co-dominant, transferable RFLP and SSR markers [21]. New EST-derived SSR markers, added to this map using a bin-mapping strategy with only 14 mapping individuals, gave a new map with 296 markers distributed in 122 bins and a density of 4.2 cM/marker [21]. There is a need for saturating the SC × PS genetic map with more markers that are amenable for large-scale genotyping, as are SNPs. In a preliminary experiment with melon, amplicon resequencing of 34 ESTs in SC and PS was used for SNP discovery, obtaining a frequency of one SNP every 441 bp and one indel every 1,666 bp [23]. The availability of more than 34,000 melon ESTs from normalized cDNA libraries from different melon genotypes and tissues [13] is a valuable resource for the identification of SNPs to be added to the current genetic map. http://www.biomedcentral.com/1471-2229/9/90 Genetic markers can also be used for variability analysis studies. In melon, there have been several attempts to elucidate intraspecific relationships among melon germplasm, using isozyme [24], RFLP [25], RAPD [26], AFLP [27] and SSR [28] markers, with SSRs the preferred marker for fingerprinting and genetic variability analysis in melon [28]. Due to the absence of a known set of SNPs in the species, this marker has not been compared with other types for variability analysis. It would be of special interest to have a set of these markers for a high-throughput system to identify the germplasm used in breeding programs, mainly from inodorus and the cantalupensis melon types. The objectives of this work were to increase the marker resolution in the melon genetic map, discovering ESTSNPs in a melon EST database, and to study the performance of a subset of EST-SNPs for variability analysis in a collection of melon accessions. Results and discussion SNP discovery Two strategies were used to discover SNPs in melon. The first was based on producing amplicons from randomly selected melon ESTs and resequencing the parental lines of the melon genetic map PI 161375 (SC) × 'Piel de sapo' T111 (PS). Primers were designed from 223 melon ESTs (Table 1). After discarding primers that did not amplify a PCR product, amplicons that did not produce high quality sequences and monomorphic amplicons, 93 ESTs (56.3%) showed at least one polymorphism between SC and PS. The second strategy was the validation of in silico SNPs from the ICuGI database [22]. Three hundred and sixty-six in silico SNPs found in the database were selected, belonging to two types of SNPs: pSNP and pSCH (Table 1; see methods). Primers were designed from 269 ESTs containing pSNP and 97 containing pSCHs. Putative in silico SNPs were validated in 51.8% and 21.3% of the amplicons for pSNPs and pSCHs, respectively. In some instances additional SNPs were detected in the sequenced regions, giving a slightly higher percentage of polymorphic amplicons (69.7% and 31.3% for pSNP and pSCH amplicons, respectively). From the ESTs reported by GonzalezIbeas et al. [13], 47.3% were obtained from two accessions of the 'Piel de sapo' cultivar type (Pinyonet and PS), and the remainder from two genotypes, the C-35 cantaloupe accession (29.3%) and the pat81 agrestis accession (23.4%). The pSNPs and pSCHs were deduced from this set of EST sequences, with a high proportion found between pat81 and 'Piel de sapo', and SNPs experimentally validated after resequencing amplicons from PS and SC. SC belongs to the agrestis melon type as the accession pat81 but has a different origin, so, as expected not all the SNPs were conserved between SC and PS, giving a pSNP validation of 51.8%. On the other hand, only 21.3% of Page 2 of 9 (page number not for citation purposes) T HJGm O (2)m BMC Plant Biology 2009, 9:90 http://www.biomedcentral.com/1471-2229/9/90 Table 1: Amplicons designed from ESTs for SNP discovery Amplicons Failed Monomorphic Polymorphic Polymorphic amplicons* In silico SNP validation Random ESTs 223 58 72 93 56.3% in silico pSNPs 269 41 69 159 69.7% 51.8% in silico pSCHs 97 14 57 26 31.3% 21.3% TOTAL 589 113 198 278 58.4% ESTs were selected at random or chosen because they contained pSNPs or pSCHs in the MELOGEN database. Columns show the number of amplicons that failed to amplify or gave bad quality sequences, and monomorphic and polymorphic amplicons between SC and PS. The percentages of polymorphic amplicons and in silico SNPs that were validated are shown in the last two columns. (*) Polymorphic amplicons rate was calculated without considering failed amplicons. the pSCHs were validated, indicating that many may represent sequencing errors or mutations introduced during the cDNA synthesis procedure. The SNPs in a subset of amplicons containing in silico SNPs between 'Piel de Sapo' and pat81 were validated using different genotyping methods (see below) rather than resequencing in PS and SC. A total of 368 amplicons (random and containing in silico SNPs) were resequenced in PS and SC and produced 177.5 kb of melon DNA, with 431 SNPs and 59 short indels, at an average of one SNP every 412 bp and one indel every 3.0 kb, (Table 2). This is in agreement with the values obtained in a previous small-scale experiment using the same two melon accessions, which gave one SNP every 441 bp and one indel every 1.6 kb [23]. SC and PS belong to the agrestis (C. melo ssp. agrestis) and inodorus (C. melo ssp. melo) melon groups, respectively, which are two of the more distant groups in the species [28]. This may explain the relatively high frequency of SNPs between the cultivars. SNP detection Various detection methods were used for genotyping the SNPs in each EST. A restriction site around the SNP position, different in the parental sequences, was used to develop a CAPS marker for 103 EST-SNPs. When more than one SNP was discovered in one amplicon, we selected the most suitable SNP for detection using CAPS. When no restriction enzyme was available to produce a CAPS marker, we used the SNaPshot SNP detection system. Seventy-seven EST-SNPs were genotyped with SNaP- shot. For 14 ESTs, PS and SC gave a different amplicon size, so they could be genotyped as SCAR markers. Four EST-SNPs were genotyped using DNA sequencing and two were converted into dCAPS. The SNP detection method used for each mapped EST-SNP is shown in Additional file 1. SNP variability Forty-five SNPs (see Additional file 2) were randomly chosen to study their variability in a set of melon accessions of worldwide cultivar and botanical types (see Additional File 3). The inodorus cultivars were overrepresented in order to assess whether SNPs between distant melon accessions (SC and PS) were also variable among more closely related genotypes. All SNPs were polymorphic and the mean major allele frequency was 0.69 (Table 3). Only one SNP (AI_24-H05) had a rare allele (frequency = 0.08), whereas the frequencies of the two alleles were similar in 28 SNPs (major allele frequency < 0.65). Average gene diversity (He) was 0.4 (ranging from 0.14 to 0.5). Forty-three SNPs yielded He > 0.20, demonstrating that most of the chosen SNPs were highly informative, as found for SNPs in rye [29] but contrasting with crops such as soybean [30] and wheat [31] where SNPs yielding rare alleles are more frequent. The mean gene diversity index for SNPs was considerably lower than the values reported for SSRs in melon (e.g. PIC = 0.58 [21], He = 0.66 [28]). To ensure the difference was not due to sampling, gene diversity indexes were estimated using a subset of genotypes that had been included Table 2: Frequency of SNPs and indels found after resequencing EST-derived amplicons Amplicons sequenced in SC and PS Length sequenced (bp) SNPs bp per SNP indels bp per indel Reference 368 177,518 431 411.9 59 3,008.8 this report 34 15,000 34 441.2 9 1,666.6 [23] Data from a previous report using the same two melon parental lines is shown as a comparison. Page 3 of 9 (page number not for citation purposes) HJHm (2)O m BMC Plant Biology 2009, 9:90 http://www.biomedcentral.com/1471-2229/9/90 Table 3: Gene diversity indexes for SNP and SSR alleles using all, inodorus or genotypes described in a previous study [28] Genotypes Marker type Major allele frequency Ho He He range all SNP 0.69 0.10 0.40 0.14–0.50 inodorus SNP 0.85* 0.07 0.15 0–0.50 group used in [28] SNP 0.63 0.09 0.47 0.16–0.50 group used in [28] SSR 0.47 0.14 0.64 0.51–0.83 Ho, observed heterozygosity; He expected heterozygosity. * Major allele frequency was only calculated for polymorphic SNPs. in a previous study with SSRs [28] (see Additional file 3). The differences in gene diversity were confirmed, demonstrating that they were intrinsic to the different marker type. SNPs are biallelic, implying that the He value can not exceed 0.5, whereas SSRs are multiallelic and so it can be higher. Haplotypes may yield higher gene diversity values than individual SNPs and provide more efficient application of SNP markers [29]. All inodorus genotypes could be distinguished with the set of SNPs, although polymorphism was notably reduced (Table 3). Fourteen SNPs were monomorphic and 18 were informative (minor allele frequency > 0.1). As most of the SNPs were discovered between the agrestis and inodorus cultivar and not within inodorus, we expected the SNP polymorphism within inodorus to be lower. Nevertheless, these results demonstrate that SNPs discovered using a germplasm sample can be successfully transferred to different germplasm samples in melon. The genetic relationships among accessions based on SNP polymorphism were investigated by cluster analysis. The NJ dendrogram (Figure 1) fits very well with previous classifications using different markers [26,28,32]. Comparing the common genotype set in [28], the average pair-wise distances based on SNPs and SSR were 0.47 and 0.64, respectively. The correlation between the two distance matrices was 0.73 (P < 0.00001) according to Mantel's test, confirming that the current SNP set is as effective as SSRs in establishing genetic relationships among melon accessions, as shown in species such as rye [29] and soybean [30]. The population structure was estimated using the STRUCTURE software [33]. The a posteriori probability of the data increased rapidly from K = 1 to 4 and begun to reach a plateau for K = 5, inferring that our collection can be divided in five populations. Genetic variability among melon germplasm seems to be highly structured. The subdivision of the accessions in 5 populations agrees with the botanical classification and the cluster analysis (Figure 1): group 1 included all the inodorus cultivars from Spain; group 2, a diverse group of traditional inodorus landraces and similar ones from the Near-East region such as elongated (chate and flexuosus) and Asiatic ananas and chandalak types; group 3, modern cantalupensis cultivars; group 4, mainly traditional varieties and wild melons from India and Africa and group 5 included conomon accessions from the Far East. The population structure should be taken into account when establishing a collection of genotypes for association mapping studies in melon and models including population structure should be used [34]. Alternatively, melon collections without structure, as we found with the inodorus melon accessions included in our studies, could be used. These results demonstrate that SNPs discovered using a small germplasm sample can be transferred to different cultivar groups, being useful for depicting genetic relationships as well as for cultivar identification. SNP mapping using a bin-mapping strategy Two hundred and seventy-eight SNP-containing ESTs (Table 1) plus twelve additional SNP-containing ESTs previously discovered between the two parental lines [22] were used for mapping in the SC × PS genetic map using 14 DHLs of the melon bin-mapping population [21]. In total, 199 EST-derived SNPs were mapped, yielding 200 new markers (Figures 2 and 3). F112 produced two SCAR markers (F112a and F112b) that mapped to groups I and V, respectively. Our previous melon bin-map contained 296 markers distributed in 122 bins, with a density of 4.2 cM/marker and 2.4 markers per bin [21]. With the addition of 35 candidate genes previously reported for resistance to virus and fruit ripening [23,35,36] and the SNPs now described, the new bin-map contains 528 markers, distributed in 145 bins, with an increased density of 2.35 cM/marker and 3.64 markers per bin. The SNP-based markers defined 23 new bins with an average bin length of 8.55 cM. Some of the new bins were located in regions with poor marker density in the previous SC × PS melon map [21], such as HS_30-B08 in group XI, AI_12-B08 in group VII, A_38-F04 in group VI or P06.05 in group III. Essentially the new version of the melon bin-map is a gene-based map, with 412 markers (78%) obtained from Page 4 of 9 (page number not for citation purposes) HJIm O (2)m BMC Plant Biology 2009, 9:90 http://www.biomedcentral.com/1471-2229/9/90 K=5 SC HER GIN PAT FREE CHT TRI KAK SEN5 MOM ZA1 ANN INB YC CAR DUL C35 VED VER DOU JPN FLEX ALF KIZ CHAN EIN AYN KRK CHA ERI ACD VLV VVG AMD BBL VHC TNI AMC ACA BBE HND RMO VCU T111 AMA PSPO PPS VVT 0.05 Figure Dendogram of 45 SNPs 1 inand 48population melon accessions structure based on the variability Dendogram and population structure based on the variability of 45 SNPs in 48 melon accessions. The neighbor-joining (NJ) tree based on Nei genetic distances [44] for the selected melon accessions is shown on the right. The subdivision based on STRUCTURE is shown on the left; each accession on the NJ is colored according to its group assignation defined from STRUCTURE analysis. gene sequences. Additionally, 114 RFLPs derived from ESTs were previously mapped in an F2 population from the cross SC × PS [37], and their approximate position can also be plotted in the corresponding bin-map. As a large proportion of the markers are codominant and based on gene sequences, this makes this map a very useful tool for melon breeding and comparative analysis in cucurbit species. With the advent of next generation sequencing technologies, SNP discovery has become more feasible in nonmodel crop species, allowing the discovery of thousands of SNPs in a single experiment [7]. In Eucalyptus grandis more than 23,000 SNPs were discovered using 454 sequencing technology, with a validation rate of 83% [38]. In melon, a preliminary analysis of 100,000 reads obtained after 454 sequencing of leaf cDNAs from SC and PS produced more than 1,000 SNPs (Garcia-Mas, unpublished). This indicates that the use of next generation sequencing technologies is the next step towards saturation of the melon genetic map. Conclusion The set of 200 SNP markers discovered and mapped have increased the marker resolution of the melon genetic map by defining new bins. The genetic map contains more than 500 gene-based codominant markers (SNPs, RFLPs and SSRs), which can be used as anchor points with other genetic maps in this species. This genetic map is also a useful resource for comparative mapping in the Cucurbitaceae, for the construction of the melon physical map and for sequencing the melon genome. Additionally, the set of SNPs has proven to be as useful as microsatellites for studying genetic relationships in melon and for varietal identification. Methods Plant material and DNA extraction The parent lines of the melon double haploid line (DHL) mapping population, PI 161375 'Songwan Charmi' (SC) and 'Piel de sapo' line T111 (PS), were used for SNP discovery [20]. Fourteen DHLs from the SC × PS segregating population were used to bin-map the SNP set [21]. The 48 melon genotypes selected for analysis with a subset of SNPs (see Additional file 3) were obtained from the germplasm collection maintained at COMAV (Valencia, Spain) and from a previous study of germplasm variability using SSRs [28]. DNA from all genotypes was extracted using a modified CTAB method [27]. DNA of the forty-eight melon accessions was extracted from leaves of five individuals per accession to take into account the genetic variability within heterogeneous accessions. SNP discovery and detection SNPs were discovered using two different strategies. Firstly, random ESTs were selected from the International Cucurbit Genomics Initiative (ICuGI) webpage [22]. Primer pairs were designed from each EST using the Primer3 software [39] with an average length of 20 nucleotides, a melting temperature around 60°C and an expected PCR product of 500–700 bp. Genomic DNA from the parental lines of the melon mapping population was amplified with each primer pair as previously described [23]. Amplified fragments were purified with Sepharose columns and sequenced using the ABI Prism BigDye Terminator Cycle Sequencing kit (Applied Biosystems, Foster City, CA, USA) in an ABI Prism 3130 sequencer (Applied Biosystems, Foster City, CA, USA). Sequences were aligned and screened for polymorphism with the Bioedit software [40]. Putative SNP positions were visually verified on the sequence chromatogram, and Page 5 of 9 (page number not for citation purposes) HJJm (2)O m BMC Plant Biology 2009, 9:90 I 0.0 II MC216 CmPABP 0.0 ECM61 MC51 CmEIL1 FR13B20 32.0 78.0 MG1 CMCTN86 CMGAN92 CM101A 47.0 CMCT505 CMCCA145 MC309 ECM233 ECM58 ECM139 CmPG4 52.0 AI_34-A07 PSI_04-D07 AI_09-G08 AI_17-E07 PSI_07-A04 F112a P01.16 ECM199 65.0 ECM173 PSI_35-C01 CMCTN53 ECM60b ECM60c TJ26 FR10P24 PSI_12-D08 AI_09-D03 CSWCT11 FR12I13 TJ27 ECM110 CmERS1 F116 AI_05-G01 20.0 24.0 PS_10-C09 AI_14-H05 P12.74 P05.79 P01.41 CmeIF(iso)4G-1 CmEIL3 CM24 CMAGN68 CMGA108 PSI_03-B09 GCM331 PS_02-H06 A_25-G05 CmXTH2 MC273 ECM223 AI_04-E05 GCM548 57.0 MC332 MC248 AI_14-E02 70.0 75.0 78.0 80.0 IV AI_24-G04 HS_10-A02 AI_14-B01 P12.96 GCM190 MC127 0.0 CSWCT10 AI_18-E05 CmEIL4 CmEXP2 TJ12b CMTAN66a CMBR83 TJ30 TJ31 MC244 GCM106 14.0 CM11 CMGA128 CMBR95 AI_08-F10 A_21-C11 CSWCT16T CMBR105 MC54 CMTA170A CMBR100 25.0 AI_33-H11 P06.15 46d_37-H067 33.0 0.0 MG34A P12.50 57.0 CMGAN94 GCM186 MC69 ECM181 MC233 20.0 25.0 MC220 ECM60a AI_06-G01 AI_14-F04 ECM205 MC365 ECM125 MC215 F028 TJ10 PS_14-A11 AI_33-E02 PS_08-G08 AI_37-A07 70.0 72.0 PSI_27-C02 CmeIF4A-3 56.0 58.0 60.0 64.0 72.0 MC211 CM131 CmeIF4A-2 81.0 90.0 91.0 95.0 CM47 CMBR89 MC344 46d_11-A08 TJ12a GCM246 AI_03-F03 AI_03-E11 98.0 108.0 MC284 CMBR35 CMAGN79 ECM53 CMAGN73 ECM185 ECM106 CM122 ECM198 86.0 ECM122 GCM336 CI_35-H04 AI_10-B10 P12.94 CmnCBP P01.11 93.0 MC219 97.0 CMTCN6 ECM134 A_23-C03 108.0 CMTC168 MC60 FR12J11 123.0 127.0 CT02B CMCTN50 PSI_28-E12 AI_37-E06 ECM137 AI_09-E07 AI_17-B12 MC294 MC212 GCM168 ECM191 ECM138 AI_11-E06 P05.27 A_03-H09 137.0 VI PSI_10-B04 CSCCT571 ECM108 ECM97 CmXTH4 PS_34-C02 A_31-E10 PS_25-E09 40.0 MC296 ECM208 CMCTN5 ECM51 CmACS5 MC252 V 12.0 CMTCN66b GCM448 CMTCN18 MC226 AI_02-C08 CmETR2 ECM184 GCM262 26.0 CMAGN61 CMAGN52 34.0 ECM197 ECM124 PSI_20-A04 GCM101 MC376 86.0 104.0 0.0 9.0 10.0 MC134 ECM85 63.0 MC340 PS_09-H05 F216 SSH1A13 MC279 AI_09-F07 18.0 41.0 III CM149 ECM230 12.0 http://www.biomedcentral.com/1471-2229/9/90 116.0 41.0 A_18-A08 15d_17-G01 CMATN101 TJ37 CMTCN9 50.0 CMCTN35 CMAT35 HS_11-A09 15d_14-B01 AI_08-G09 P02.22 CI_19-H12 SSH9G15 ECM129 ECM92 MC256 CmeIF(iso)4E ECM142 CMGAN3 MC4 70.0 ECM203 GCM622 CmETR1 ECM109 GCM295 CmeIF4G PS_15-B02 PS_03-B08 MC8 ECM52 FR11A2 MC21 GCM303 GCM255 ECM81 GCM302 ECM135 CMTCN41 CMCT123 CI_56-B01 FR14P22 AI_19-F11 PS_19-B07 AI_03-B03 15d_29-E06 MC224 AI_05-H08 HS_20-C04 HS_05-B07 A_38-F04 CMTCN2 MRGH63 F112b CSWTA02 CSWCTT02T AI_13-H12 CMBR15 CMBR107 CMTAA166 97.0 ECM132 ECM178 GCM112 AI_13-F02 PS_28-B07 P01.45 HS_06-D02 CmERF3 MC42 105.0 CMTAAN100 CMBR123 CMCTN38 115.0 ECM231 HS_33-D11 PSI_19-F05 PS_07-E07 CmEthInd GCM155 135.0 CMCTN4 PSI_11-D12 141.0 Figure 2 bin map of Cucumis melo obtained by selective genotyping of fourteen DHLs EST-SNP EST-SNP bin map of Cucumis melo obtained by selective genotyping of fourteen DHLs. Linkage groups are represented by vertical bars, divided in bins defined by the joint genotype of the selected DHLs. The mapped SNPs in this report are shown in bold. Underlined markers are candidate genes previously reported [23,35,36]. The other markers have been described in [21]. Genetic distances are shown on the left, indicating the position of the last marker included in the bin according to the framework map in [21]. Markers defining new bins are shown in italics. The hypothetical position of the last marker of these bins is indicated by a dashed horizontal line within the linkage group bar, without the genetic distance. the genomic sequences compared with the original EST sequence to identify any introns. In the second strategy, in silico SNPs previously identified [13] using EST2uni [41] were classified as i) pSNPs, corresponding to SNPs present in at least two EST sequences from the same genotype in a given contig and with the same base change and ii) pSCHs, corresponding to single nucleotide variations in sequence that did not follow the above criteria for pSNPs. Selected pSNPs and pSCHs were verified in most cases after resequencing the parental lines of the melon mapping population. For a small subset, the SNP was verified with an appropriate SNP detection method. Bioedit software was used to generate restriction maps from sequences obtained from SC and PS. SNPs (or indels) showing differential restriction maps were used to develop cleaved amplified polymorphic sequence (CAPS) markers. When no differential restriction maps were available, the ABI Prism SNaPshot ddNTP Primer Extension Kit (Applied Biosystems) was used for SNP genotyping [23]. Markers F112, 46d_11-A08, FR12J11, 15d_17-G01, P01.45, PSI_26-B12, F012, PS_18-F05, PS_16-C09, F088, A_02-H11, AI_13-G03 and FR15D10 produced amplicons of different sizes in the parental lines, which were not sequenced and were genotyped as sequence characterized amplified region markers (SCARs) after electrophoresis in agarose gels or using a LI-COR IR2 sequencer (Li-Cor Inc, Lincoln, Nebraska, USA). Markers PSI_12-D08 and PSI_35-F11 were converted into dCAPS markers [42]. Markers F028, F149, F080 and PSI_25-B05 were genotyped using direct sequencing. Page 6 of 9 (page number not for citation purposes) HJKm O (2)m BMC Plant Biology 2009, 9:90 VII 5.0 8.0 VIII ECM50 F072 GCM181 MC373 ECM79 AI_05-F11 CmeIF(iso)4G-2 A_06-A03 AI_12-B08 AI_27-F07 PSI_26-B12 3.0 6.0 16.0 MC311 MC44 CMAGN75 ECM182 ECM227 AI_25-C11 F271 P06.69 39.0 47.0 48.0 51.0 55.0 60.0 IX 15d_01-B03 A_30-G06 CSGA057 CMBR24 CMBR7 ECM88 P4.35 PS_28-E01 F125 PSI_29-D11 0.0 F080 PS_18-F05 TJ3 MC301 ECM217 ECM128 PSI_23-A11 HS_25-A10 CmAco3 13.0 MC68 TJ2 CmACS3 CI_33-B09 29.0 ECM221 AI_02-A08 MC253 CMTCN30 PSI_33-F04 HS_04-F11 41.0 CSAT425B ECM84 TJ38 ECM77 CMCAN90 CMBR53 CMBR27 P06.02 AI_03-G06 CmACS2 CMAGN21 CMBR84 GCM521 54.0 F149 F012 CSWCT12T CI_08-C08 CM139 AI_08-H11 ECM204 68.0 76.0 http://www.biomedcentral.com/1471-2229/9/90 CMGA15 ECM172 CmERF2 PSI_37-G01 CI_37-H11 77.0 CMTC13 AI_21-G05 AI_21-D08 P01.8 35.0 MC356 MC11 MC78 ECM200 CMAT141 PSI_25-H03 94.0 0.0 10.0 17.0 ECM150 ECM177 MRGH7 CM98 ECM66 PSI_12-C05 AI_17-B03 AI_39-A12 PSI_23-G11 31.0 FR18J20 A_17-A08 F036 AI_04-D08 35.0 54.0 57.0 61.0 PSI_21-D01 TJ33 0.0 CMTCN62 MC146 ECM210 P05.50 CMTC160 ECM63 ECM183 P4.39 A_02-H01 MC17 CSWCT01 CSWCT22A HS_30-B08 CMTCN67 MC264 CMGAN12 MC375 CMAGN45 CmXTH5 CMGA172 ECM228 MC112 MC67 CM40 CMTA134B CMCTN65 CMGA165 ECM232 GCM153 ECM49 ECM116 ECM220 ECM101 GCM344 AI_38-B09 F088 46d_21-E02 CmEXP3 CM101B CMTCN8 31.0 34.0 42.0 HS_39-A03 CMATN56 CmEXP1 97.0 TJ29 MC330 HS_23-D06 FR15D10 CSWCT18B CmeIF4A-1 29.0 HS_35-E11 AI_22-A08 A_05-A02 FR12O13 CmACO5 MC231 ECM164 HS_02-E07 PS_24-E03 PSI_41-B07 49.0 CMATN89 MC349 CMGA104 P06.79 PSI_35-H10 66.0 MC325 71.0 CMTCN14 CMAGN33 CMAGN32 CMAGN80 ECM123 ECM218 P02.03 FR14F22 MC93 MC265 ECM147 ECM145 A_08-D10 15d_27-B02 AI_13-G03 93.0 CSAT425A MC286 CI_57-E03 53.0 62.0 CM91 CMTCN1 CMCTN7 AI_21-E10 CmERF1 CmPME3 MC132 GCM206 PSI_22-B02 PSI_12-D12 5A6U nsv MC320 ECM67 ECM105 CmeIF4E AI_35-A08 AI_09-G07 15d_01-B03 FR12P24 17.0 76.0 102.0 XII ECM175 MC149 ECM78 0.0 PS_16-C09 PSI_35-F11 2.0 PS_33-E12 AI_36-F12 8.0 CMCTN71 CMCTN19 69.0 ECM55 MC138 99.0 MC92 CMTC47 ECM186 P05.64 A_04-B10 FR13O21 CMACC146 GCM241 MC208 CMAG59 F013 A_32-B01 CI_58-C10 XI HS_23-E06 ECM86 ECM82 PS_15-H02 PS_40-E11 MRGH21 A_08-H06 ECM56 F129 MC125 PS_19-E06 P05.15 AI_16-D09 X 81.0 P02.75 AI_08-F01 A_20-H12 AI_35-E03 P01.17 MC237 CMATN22 110.0 Figure 3 bin map of Cucumis melo obtained by selective genotyping of fourteen DHLs EST-SNP EST-SNP bin map of Cucumis melo obtained by selective genotyping of fourteen DHLs. Linkage groups are represented by vertical bars, divided in bins defined by the joint genotype of the selected DHLs. The mapped SNPs in this report are shown in bold. Underlined markers are candidate genes previously reported [23,35,36]. The other markers have been described in [21]. Genetic distances are shown on the left, indicating the position of the last marker included in the bin according to the framework map in [21]. Markers defining new bins are shown in italics. The hypothetical position of the last marker of these bins is indicated by a dashed horizontal line within the linkage group bar, without the genetic distance. SNP mapping SNPs and indels were mapped by selective genotyping using the bin-mapping strategy [43], adapted for the melon mapping population [21]. Fourteen out of 72 DHLs from the melon mapping population were selected to obtain the maximum resolution with a minimum number of genotypes. SNPs and indels were placed in the bin map by visual inspection of the genotypes predicted by the markers and genotypes in the bin set. Genetic variability analysis Forty-five SNPs from 44 amplicons (two SNPs were selected from F241) were chosen for genetic variability analysis. SNPs were genotyped as CAPS or by pyrosequencing as shown in Additional file 2. Thirty SNPs, described in Additional file 1, were used. Twelve SNPs that were not polymorphic between SC and PS were also included in the variability analysis, and the primers for each amplicon are provided in Additional file 2. The SNPs CmERF1, CmPm3 and CmXTH5 have been previously described [36]. Eight SNPs were genotyped by minisequencing the region surrounding the polymorphism (two SNPs were detected for F241 in the same reaction). Pyrosequencing was performed using a PSQ™ HS 96 system (Pyrosequencing AB, Uppsala, Sweden) following the manufacturers' instructions. Primers were designed with the Pyrosequencing™ Assay Design Software (Biotage AB, Uppsala, Sweden). One of the amplifying primers was 5' end labeled with biotin, allowing the immobilization of the fragment onto M-280 streptavidin coated Sepharose™ dynabeads (Dynal AS, Oslo, Norway). The genotyping primer was hence designed to anneal several nucleotides upstream of the SNP. After denaturation of the streptavidin-captured PCR fragments, the single stranded DNA fragments were released into the wells of the PSQ HS 96 plate. Pyrosequencing was performed using the PSQ HS SNP Reagent kit (Pyrosequencing AB, Uppsala, Sweden), and bioluminometric quantification of pyrophosphate (Ppi) released as a result of nucleotide incorporation during DNA synthesis was measured with the PSQ™ HS 96 system. Page 7 of 9 (page number not for citation purposes) HJLm (2)O m BMC Plant Biology 2009, 9:90 http://www.biomedcentral.com/1471-2229/9/90 Allele frequencies, major allele frequency, gene diversity (measured as expected heterozygosity, He [44]), genetic distances and neighbor-joining (NJ) tree were calculated using Powermarker 3.25 [45]. The NJ tree was plotted with MEGA 3.0 [46]. Distance matrices were compared by the Mantel test [47]. Additional file 2 SNP markers used for genotyping the melon accessions. The EST from where the SNPs were discovered, the genotyping method (CAPS or pyrosequencing), linkage group where the marker maps to, and source of the marker are given. For unmapped SNP markers, the amplicon primer sequences are given. For SNP markers genotyped using pyrosequencing, forward, reverse and internal primers were used for genotyping. 5'bio: Forward or reverse primer was 5' labeled with biotine. ST1: Additional file 1. Click here for file [http://www.biomedcentral.com/content/supplementary/14712229-9-90-S2.xls] The number of populations in our collection was deduced with the STRUCTURE software [33]. This package uses a Bayesian clustering approach to identify subpopulations and to assign individuals to these populations on the basis of their genotypes. Given a sample of individuals, K populations are assumed (where K may be unknown) and individuals are assigned to these populations. A posteriori probability for each K (Pr(K)) can be calculated, which is very small for K values lower than the appropriate value. Usually, the researcher fixes a minimum K (for example K = 1), recording Pr(K) after the analysis, and tests increasing Ks, plotting K against Pr(K). The final K is defined when Pr(K) reaches a plateau for higher K values. Consequently, in the current report, several number of populations (from K = 1 to 8) were tested with the software and the total number of populations was set when the probability reached a plateau for higher K. Additional file 3 Forty-eight melon accessions that were examined in this study. Plant assignation (or common name), code used in the current study, accession number from the respective gene banks, cultivar group, origin and seed bank donor (COMAV, Instituto de Conservación y Mejora de la Agrodiversidad Valenciana, Valencia, Spain; USDA/ARS/NCRPIS, North Central Regional Plant Introduction Station, Ames, IA, USA; IPK, Institute of Plant Genetics and Crop Plant Research, Gatersleben, Germany; INRA, Institute Nationale de la Recherche Agronomique, Montfavet, Avignon, France; Semillas Fitó SA, Barcelona, Spain; ARO, Agricultural Research Organization, Ramat Yishay, Israel) are specified for each genotype. Accessions marked with (*) were previously used by Monforte et al. (2003) for an SSR study. Click here for file [http://www.biomedcentral.com/content/supplementary/14712229-9-90-S3.xls] Authors' contributions WD discovered and mapped the SNPs and performed the genotyping for the variability analysis. CE and MGT discovered and mapped SNPs. CR discovered SNPs. IFS mapped SNPs. DGI identified and selected in silico SNPs. JB carried out the bioinformatics analyses for in silico SNPs. AJM performed the variability analysis, coordinated the SNP mapping and participated in the drafting of the manuscript. MBP prepared DNAs for the melon accessions and participated in the genotyping for the variability analysis and in the drafting of the manuscript. JGM, PA, FN, MBP and MAA were involved in the conception of the study. JGM is the principal researcher of this work, supervised it and wrote the manuscript. All authors read and approved the final manuscript. Acknowledgements This work was supported by a grant from the Ministerio de Educación y Ciencia (Spain) (GEN2003-20237-C06). WD is recipient of a postdoctoral fellowship from the Centre de Recerca en Agrigenòmica CSIC-IRTA-UAB (Spain). CR is recipient of a Juan de la Cierva grant from the Ministerio de Educación y Ciencia (MEC) (Spain). DGI and CS are recipients of pre-doctoral fellowships from MEC (Spain). IFS is recipient of a pre-doctoral fellowship from INIA (Spain). We are grateful to Armand Sanchez and Anna Mercader (UAB) for their help with the pyrosequencing analysis. References 1. 2. 3. Additional material Additional file 1 SNPs markers mapped in the SC × PS genetic map. Shown here, for each SNP marker: the EST and accession number from where it was obtained; best BlastX hit and E-value for each EST; amplicon primer sequences; SNP/indel position; SNP detection method; linkage group and BIN where the marker maps to. asequence available in [22] or http:// www.melogen.upv.es without accession number. bSNPs published by Morales et al (2004). cSNP position is provided when located in exons and referred to EST in first column. dthird primer was used for SNaPshot genotyping. Click here for file [http://www.biomedcentral.com/content/supplementary/14712229-9-90-S1.xls] 4. 5. 6. 7. 8. Brookes AJ: The essence of SNPs. Gene 1999, 234(2):177-186. Ganal MW, Altmann T, Roder MS: SNP identification in crop plants. Curr Opin Plant Biol 2009, 12(2):211-217. Batley J, Barker G, O'Sullivan H, Edwards KJ, Edwards D: Mining for single nucleotide polymorphisms and insertions/deletions in maize expressed sequence tag data. Plant Physiol 2003, 132(1):84-91. Borevitz JO, Liang D, Plouffe D, Chang HS, Zhu T, Weigel D, Berry CC, Winzeler E, Chory J: Large-scale identification of single-feature polymorphisms in complex genomes. Genome Res 2003, 13(3):513-523. Choi IY, Hyten DL, Matukumalli LK, Song Q, Chaky JM, Quigley CV, Chase K, Lark KG, Reiter RS, Yoon MS, et al.: A soybean transcript map: gene distribution, haplotype and single-nucleotide polymorphism analysis. Genetics 2007, 176(1):685-696. Velasco R, Zharkikh A, Troggio M, Cartwright DA, Cestaro A, Pruss D, Pindo M, Fitzgerald LM, Vezzulli S, Reid J, et al.: A high quality draft consensus sequence of the genome of a heterozygous grapevine variety. PLoS ONE 2007, 2(12):e1326. Barbazuk WB, Emrich SJ, Chen HD, Li L, Schnable PS: SNP discovery via 454 transcriptome sequencing. Plant J 2007, 51(5):910-918. Hayes B, Lærdahl JK, Lien S, Moen T, Berg P, Hindar K, Davidson WS, Koop BF, Adzhubei A, Høyheim B: An extensive resource of sin- Page 8 of 9 (page number not for citation purposes) HJMm O (2)m BMC Plant Biology 2009, 9:90 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. gle nucleotide polymorphism markers associated with Atlantic salmon (Salmo salar) expressed sequences. Aquaculture 2007, 265:82-90. Wang S, Sha Z, Sonstegard TS, Liu H, Xu P, Somridhivej B, Peatman E, Kucuktas H, Liu Z: Quality assessment parameters for ESTderived SNPs from catfish. BMC Genomics 2008, 9:450. Yamamoto N, Tsugane T, Watanabe M, Yano K, Maeda F, Kuwata C, Torki M, Ban Y, Nishimura S, Shibata D: Expressed sequence tags from the laboratory-grown miniature tomato (Lycopersicon esculentum) cultivar Micro-Tom and mining for single nucleotide polymorphisms and insertions/deletions in tomato cultivars. Gene 2005, 356:127-134. Pavy N, Parsons LS, Paule C, MacKay J, Bousquet J: Automated SNP detection from a large collection of white spruce expressed sequences: contributing factors and approaches for the categorization of SNPs. BMC Genomics 2006, 7:174. Arumuganathan K, Earle ED: Nuclear DNA content of some important plant species. Plant Mol Biol Rep 1991, 9:208-218. Gonzalez-Ibeas D, Blanca J, Roig C, Gonzalez-To M, Pico B, Truniger V, Gomez P, Deleu W, Cano-Delgado A, Arus P, et al.: MELOGEN: an EST database for melon functional genomics. BMC Genomics 2007, 8:306. van Leeuwen H, Monfort A, Zhang HB, Puigdomenech P: Identification and characterisation of a melon genomic region containing a resistance gene cluster from a constructed BAC library. Microcolinearity between Cucumis melo and Arabidopsis thaliana. Plant Mol Biol 2003, 51(5):703-718. Mascarell-Creus A, Cañizares J, Vilarrasa J, Mora-García S, Blanca J, Gonzalez-Ibeas D, Saladié M, Roig C, Deleu W, Picó B, et al.: An oligo-based microarray offers novel transcriptomic approaches for the analysis of pathogen resistance and fruit quality traits in melon. BMC Genomics in press. Eduardo I, Arus P, Monforte AJ: Development of a genomic library of near isogenic lines (NILs) in melon (Cucumis melo L.) from the exotic accession PI161375. Theor Appl Genet 2005, 112(1):139-148. Wang YH, Thomas CE, Dean RA: A genetic map of melon (Cucumis melo L.) based on amplified fragment length polymorphism (AFLP) markers. Theor Appl Genet 1997, 95:791-798. Danin-Poleg Y, Reis N, Baudracco-Arnas S, Pitrat M, Staub JE, Oliver M, Arus P, deVicente CM, Katzir N: Simple sequence repeats in Cucumis mapping and map merging. Genome 2000, 43(6):963-974. Perin C, Hagen S, De Conto V, Katzir N, Danin-Poleg Y, Portnoy V, Baudracco-Arnas S, Chadoeuf J, Dogimont C, Pitrat M: A reference map of Cucumis melo based on two recombinant inbred line populations. Theor Appl Genet 2002, 104(6–7):1017-1034. Gonzalo MJ, Oliver M, Garcia-Mas J, Monfort A, Dolcet-Sanjuan R, Katzir N, Arus P, Monforte AJ: Simple-sequence repeat markers used in merging linkage maps of melon (Cucumis melo L.). Theor Appl Genet 2005, 110(5):802-811. Fernandez-Silva I, Eduardo I, Blanca J, Esteras C, Pico B, Nuez F, Arus P, Garcia-Mas J, Monforte AJ: Bin mapping of genomic and ESTderived SSRs in melon (Cucumis melo L.). Theor Appl Genet 2008, 118(1):139-150. The International Cucurbit Genomics Initiative (ICuGI) [http://www.icugi.org] Morales M, Roig E, Monforte AJ, Arus P, Garcia-Mas J: Single-nucleotide polymorphisms detected in expressed sequence tags of melon (Cucumis melo L.). Genome 2004, 47(2):352-360. Staub JE, Box J, Meglic V, Horejsi TF, Mccreight JD: Comparison of isozyme and random amplified polymorphic DNA data for determining intraspecific variation in Cucumis. Genet Res Crop Evol 1999, 44:257-269. Neuhausen SL: Evaluation of restriction fragment length polymorphisms in Cucumis melo. Theor Appl Genet 1992, 83:379-384. Stepansky A, Kovalski I, Perl-Treves R: Intraspecific classification of melons (Cucumis melo L.) in view of their phenotypic and molecular variation. Plant Syst Evol 1999, 217:313-332. Garcia-Mas J, Oliver M, Gómez H, de Vicente MC: Comparing AFLP, RAPD and RFLP markers to measure genetic diversity in melon. Theor Appl Genet 2000, 101:860-864. Monforte AJ, Garcia-Mas J, Arús P: Genetic variability in melon based on microsatellite variation. Plant Breeding 2003, 122:153-157. http://www.biomedcentral.com/1471-2229/9/90 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. Varshney RK, Beier U, Khlestkina EK, Kota R, Korzun V, Graner A, Borner A: Single nucleotide polymorphisms in rye (Secale cereale L.): discovery, frequency, and applications for genome mapping and diversity studies. Theor Appl Genet 2007, 114(6):1105-1116. Yoon MS, Song QJ, Choi IY, Specht JE, Hyten DL, Cregan PB: BARCSoySNP23: a panel of 23 selected SNPs for soybean cultivar identification. Theor Appl Genet 2007, 114(5):885-899. Ravel C, Praud S, Murigneux A, Canaguier A, Sapet F, Samson D, Balfourier F, Dufour P, Chalhoub B, Brunel D, et al.: Single-nucleotide polymorphism frequency in a set of selected lines of bread wheat (Triticum aestivum L.). Genome 2006, 49(9):1131-1139. Monforte AJ, Eduardo I, Abad S, Arus P: Inheritance mode of fruit traits in melon-heterosis for fruit shape and its correlation with genetic distance. Euphytica 2005, 144:31-38. Pritchard JK, Stephens M, Donnelly P: Inference of population structure using multilocus genotype data. Genetics 2000, 155(2):945-959. Pritchard JK, Stephens M, Rosenberg NA, Donnelly P: Association mapping in structured populations. Am J Hum Genet 2000, 67(1):170-181. Essafi A, Diaz-Pendon JA, Moriones E, Monforte AJ, Garcia-Mas J, Martin-Hernandez AM: Dissection of the oligogenic resistance to Cucumber mosaic virus in the melon accession PI 161375. Theor Appl Genet 2009, 118(2):275-284. Moreno E, Obando JM, Dos-Santos N, Fernandez-Trujillo JP, Monforte AJ, Garcia-Mas J: Candidate genes and QTLs for fruit ripening and softening in melon. Theor Appl Genet 2008, 116(4):589-602. Oliver M, Garcia-Mas J, Cardus M, Pueyo N, Lopez-Sese AL, Arroyo M, Gomez-Paniagua H, Arus P, de Vicente MC: Construction of a reference linkage map for melon. Genome 2001, 44(5):836-845. Novaes E, Drost DR, Farmerie WG, Pappas GJ Jr, Grattapaglia D, Sederoff RR, Kirst M: High-throughput gene and SNP discovery in Eucalyptus grandis, an uncharacterized genome. BMC Genomics 2008, 9:312. Rozen S, Skaletsky H: Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000, 132:365-386. Hall TA: BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 1999, 41:95-98. Forment J, Gilabert F, Robles A, Conejero V, Nuez F, Blanca JM: EST2uni: an open, parallel tool for automated EST analysis and database creation, with a data mining web interface and microarray expression data integration. BMC Bioinformatics 2008, 9:5. Neff MM, Neff JD, Chory J, Pepper AE: dCAPS, a simple technique for the genetic analysis of single nucleotide polymorphisms: experimental applications in Arabidopsis thaliana genetics. Plant J 1998, 14(3):387-392. Howad W, Yamamoto T, Dirlewanger E, Testolin R, Cosson P, Cipriani G, Monforte AJ, Georgi L, Abbott AG, Arus P: Mapping with a few plants: using selective mapping for microsatellite saturation of the Prunus reference map. Genetics 2005, 171(3):1305-1309. Nei M, Tajima F, Tateno Y: Accuracy of estimated phylogenetic trees from molecular data. II. Gene frequency data. J Mol Evol 1983, 19(2):153-170. Liu K, Muse SV: PowerMarker: an integrated analysis environment for genetic marker analysis. Bioinformatics 2005, 21(9):2128-2129. Tamura K, Dudley J, Nei M, Kumar S: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 2007, 24(8):1596-1599. Mantel N: The detection of disease clustering and a generalized regression approach. Cancer Res 1967, 27(2):209-220. Page 9 of 9 (page number not for citation purposes) HJNm (2)O m TT T M m *m !-,m *-1m !# "-0#1m 32'*'8"-1m .0m *1m +.*'$'!!'-,#1m "#m !"m %#,m .0m B1/3#"m "#m +32,2#1mYm,m*m!-*3+,m"#m*m'8/3'#0"m#*m,-+ 0#m"#m*-1m!# "-0#1m7mm*m"#0#!&m*1m 1#!3#,!'1m!-00#1.-,"'#,2#1Ymm -+ 0#m # "-0m $ETB$0T ,/+(">-T m ,20-Gjm m !Kdm m ,20-,G#4jNFFm m 3**!KdjMFFm m $ETC.T ,/+(">-T m ,20-,Gjm m !Idm m ,20-,G-0jMFFm m 3**!IdjNFFm m $P(1.QET m '1-Jm m '1-Jm m '1-JjMFFm m '1-JjNFFm m BT m GjGm m GjGm m GjNjMFFm m GjNjNFFm m T m jLm m IdjHm m JjMFFm m jNFFm m HJOm O (2)m M!m+.A,m"#mm %*HmGKm+m *mKFFm+m 0'1mGFFm+m #*2',mFYFGPm T M"T 09$'!-m "#m *m "'*3!'A,m ,#!#10'm "#m #,8'+m ()m #,m $3,!'A,m "#m *m !-,!#,20!'A,m "#m m - 2#,'"m#,m*m-.OYm#.#,"'#,"-m"#m*-1m,%m"#m.0-"3!2-m- 2#,'"-1m#,m*mm"# #m3101#m 3,m!-,!#,20!'A,m"#!3"m"#m#,8'+m.0m/3#m*m"'%#12'A,m1#mA.2'+Ym^2-1m.0-.-0!'-,"-1m .-0m#*m%03.-m"#*mZm0Ym "#*m#,"&+,#_Ym T m m M#T+.A,m"#m"'*3!'A,m"#m*m#,8'+m()O m KFm+m0'1m*m.Nm GFFm+m*m GFmxm,*Hm FYFGPm0'2-,mjGFFm KFPm*'!#0-*m HFmx%i+mm!#2'*"-m T HKFm (2)O m M$m+.A,m"#m0#!!'A,m.0m*m"'%#12'A,m!-,m()O O Gm#.#1m.MZKm FYGm%Jm FYFHPm0'2-,m^jGFF_m FYGm*m mHm m M%m+.A,m"#m#620!!'A,m"#mm-7*#m m HPmm GZJm*m HF+mm GFF+m0'1j*m^.mNYFm_m (3120mmmNYFFZm32-!*40m7m"#(0m#,$0'0Ym',*+#,2#m@"'0mFYHPm"#muj+#0!.2-#2,-*m m M&m+.A,m"#m*4"-m-7*#m m 2,-*mMLPm !#22-m+A,'!-mGF+m T M'm83*m"#m!0%m.0m%#*#1m"#m%0-1m m 83*m"#m 0-+-$#,-*mFYLPm^.i4_m *'!#0-*mMFPm^4i4_m mFYHPm^4i4_m mFYK6m mHFm+m m M(m+.A,mGFm m 0'1mGm mGF+m !jIHmFYGHm m m M)T *m!-,m*1m1#!3#,!'1m"#m*-1m!# "-0#1m32'*'8"-1m"30,2#m*m1#!3#,!'!'A,m"#m!"m%#,[m m O Y(YGmGO m HKGm O (2)m -+ 0#m!# "-0m #!3#,!'m m m HFMm m Hm m Im m HFNm m Im m Im m Lm m Jm m Jm m m m IdjHm m m O Y(YHmI#-)J>O T -+ 0#m!# "-0m #!3#,!'m 1-Jm m 1-Jm m 1-Jm m 1-Jm m T O O Y(YIm;O T -+ 0#m!# "-0m #!3#,!'m GjGm m GjNm m GjNm m GjHm m GjGm m GjJm m GjKm m GjJm m GjLm m GjKm m GjIm m GjLm m GjIm m m m T M*T BBDT 40'#""#1m 31"1m .0m #*m !-m .#02#,#!'#,2#1m *m ,!-m "#m %#0+-.*1+m "#*m Ym m HKHm (2)O m m >#(&.T#$T 03/.T .,!0$T+." +T ;1T#$T.0;&$-T mHKJm "3"'+m m $%,'129,m mGHKOKGm +#*-j!&,"*!)m m $%,'129,m JHJm +#*-j!,2*3.]]m .(#.#0m * ,'m -*jNJm +#*-j",m +#*A,m -*'4'm KIKm +#*-j!,2*3.]]m m 3*%0'm HFLm !-,-+-,m m &',m LGNNKJm !-,-+-,m -,%2',m &',m KGFm +#*-m "',(j- '!,m 0-!'m GJMLm +#*-m m !3"-0m HNNHIIm +#*-m $0m&)'+m %'.2-m GONm !,2*3.#,1'1m jjGGm +#*-m #*-,m,,20'm #-0%'m jIGJJHMm +#*-j!,2*3.]]m -*(-,'28m #-0%'m mGNKGGGm +#*-j2' '1&]]m m &,m KIm +#*-j!,2*3.]]m jjHm +#*-j!,2*3.]]m mGIIm ',-"-031m mIFKm !,2*3.#,1'1j+#0'm 8C12m,,18m 3,%0>m mJINm +-+-0"'!m &0 3(m ,"'m HHKm $*#63-131m m ,"'m GHJGGHm +-+-0"'!m m ,"'m mGLJIHFm !&'2-j%0#12'1m m ,"'m mIJJm $*#63-131m &'0m20387m 0)m mIJOm $*#63-131m m 0)m mIKKm +#*-Zm',-"j1'2'!-m m 0)m mGJFLIHm !,2*3.#,1'1m m 09,m mILIm "8&30mj!&2#m !0-1#**-m 2*'m IMHm +#*-m !3!3+088-m 2*'m mHLLOJMm !2*3.#,1'1m m .A,m mJHFGMLm !-,-+-,j+)35m %',1#,j+)35m .A,m ""$1(>-T ,2*-3.m"#m #**#%0"m m^-32&m *),_m #*-,m 31!2#**-m 3)-0"',,7#m 1*-4/3'm 0#!'m 32#+*m 3,%0>m HKIm O HKJm (2)m jjGFm +#*-m +#12,'m 8(129,m 2NGm %0#12'1m %0#12'1m.2jNGm -0#m HOJm !,2*3.#,1'1m &'0m ' 'm mJOFINNm !,2*3.m ,),'m *'m IINm !&,"*)m m -,%-*'m $0j!jGm +#*-j0#2'!3*231m m 003#!-1m jHNMm %0#12'1m m '%#0'm FJNJJm +#*-m +#*-m -023%*m 1!m"#m jKLGOMm +#*-m mGLNm +#*-m -0;m 31'm HKOm !,2*3.m .#*1',(m 31'm mHMLLLFm !&,"*)m m 31'm mKFLJLFm !,2*3.#,1'1m )34'1,)m 31'm mJILKIJm %0#12'1m m #,#%*m mHNHJJNm +#*-m m 30m$0'!m NHFMm ',-"-031m @m3*!#m 1.@m jFJOm ',-"-031m -,#7j"#5m 1.@m jjGFOm ',-"-031m #*A,m!-!m 1.@m jjGIIm !,2*3.m jjMm ',-"-031m !04*&-m #*A,m#1!0'2-m -*-0-1-m #0"#m%-0"-m *,!-m -023%*m 1.@m 1.@m jjMFm ',-"-031m jjNm ',-"-031m jjOFm ',-"-031m #+.0,'**-m 1.@m jGONm ',-"-031m '*-m!00#2#m 1.@m jGOOm ',-"-031m *,!-m*'1-m 1.@m jHJGm ',-"-031m jHNGGjGjm 1.@m jKKFm !,2*3.]]m #*-,m83!0"-m 1.@m jLHm ',-"-031m "30m+0'**m 1.@m jjGOm ',-"-031m -**#031m 1.@m jjHLm !,2*3.#,1'1m #*Amm 1.@m jIIm ',-"-031m #,"0*m 1.@m jjIOm ',-"-031m 30#,2#,-m 1.@m #1!0'230"-m #,"0*m,#%0-m"#m ',4'#0,-m 1.@m 1.@m (2)O m &mGMm ',-"-031m *,!-m &GIm ',-"-031m &Km ',-"-031m jjGm !,2*3.#,1'1m jGMm ',-"-031m #*-,m.'@-,!'**-m 1.@m jHKm ',-"-031m +0'**-m 1.@m jjHIm ',-"-031m *,!-m 1.@m jjKFm ',-"-031m -!&3#*-m 1.@m jjKIm ',-"-031m mjjHOm ',-"-031m #*-,m+0'**m 1.@m jjGm ',-"-031m *+-,2#m 1.@m jjIm ',-"-031m '*-m00#2#m 1.@m jIOm ',-"-031m #0"#m.',2-m 1.@m #*-,m,#%0-m"#m ',4'#0,-m '.m"#m-0-m #0"#(-j!1#0-m 07"-m 0%-m"#m '**!-,#(-1m +0'**-m 1.@m 1.@m 1.@m 1.@m 1.@m 1.@m jjJKm ',-"-031m 0'!-m ',-"-031m 0';Am+**-0/3',m 1.@m 0,!#1#2m m m 1.@m YmNHFNm ',-"-031m ,4#0,'8-m 1.@m YmNHGJm ',-"-031m -+B,m 1.@m YmNHGKm ',-"-031m ,4#0,m 1.@m YmNHGMm ',-"-031m -*1m 1.@m YmNHHGm ',-"-031m -!&3#*-m 1.@m jjGMm ',-"-031m +0'**-m-0-m 1.@m 3!jHGm ',-"-031m 0-!&#2m 1.@m jjIKm ',-"-031m +0'**-m!,0'-m 1.@m jjILm ',-"-031m #,"0*m 1.@m jjJJm ',-"-031m #,"0*m20"'-m 1.@m mjjGILm ',-"-031m #*A,m+0'**-m 1.@m jjGIGm $*#63-131m *$'!-1m!-+ 0-m 1.@m jjOm +#*-m #*-,m2-)1&m "1&')'129,m JGLm 22')m m 3,'!'m mGLMFKMm $*#63-131m !3)m 30/3>m mGLOIFKm ',-"-031m )'0)%!m 30/3>m +,!&"-m HKKm O m T HKLm (2)m mGLOIHOm ',-"-031m 5',2#0m27.#m 30/3>m mGLOIIGm +#*-Zm',-"-031m *m2'+ 1m 30/3>m mGLOILNm +#*-mZm',-"-031m 11+ #7m 30/3>m mKFLJKOm !,2*3.#,1'1m m !0,'m !3+JLNm +#*-m 2328m3.0#+#m m !3+JMJm +#*-Zm!2*3.#,1'1m !3+KFFm !,2*3.#,1'1m -*"#,m-,#7m m ,1*IFFIHm !,2*3.#,1'1m 2-.+0)m m 1'!jKm !&,"*!)m )-2!&m 8 #)'129,m 1'!jLm +#0'm )'8'*j303)m 8 #)'129,m 7HNKm +#*-m m 3%-1*4'm mKFKLFHm %0#12'1m m + 'm mJNHJHOm %0#12'1m m '+ 3#m -*"#,m &+.*',m m (2)O m T TT T M m-1'!'A,m"#m*1m$+'*'1m+32,2#1m#,m*1mHKm.*!1m/3#m!-,12'237#,m*m.- *!'A,m"#mm "#m //'#-O '&)O #* -0"m #,m #12#m 20 (-Ym 1m 1'%*1m '"#,2'$'!,m #*m *3%0m "#m !0#!'+'#,2-m "#m *m $+'*'mHm^[Zm[m#+'**1m'2AmY_Ymg+'*'1m!-,m.-!-mm-m.09!2'!+#,2#m,3*-Ym m Gm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm Gm GFm HGm IIm JHm KGm LFm MIm NIm OGm GFJm GGMm m Hm GGm HIm IJm JJm KIm LJm MJm NJm OHm GFNm GGNm m Im GHm HLm IKm JKm KJm LKm MLm NKm OJm GFOm GGOm m Jm GJm HMm ILm JLm KKm LLm MMm NLm OLm GGGm GHFm m Km GKm HOm IMm JMm KLm LNm MOm NMm OMm GGIm GHGm m Lm GLm IFm INm JNm KMm MFm NFm NNm OOm GGJm GHHm m Mm GMm IGm IOm JOm KNm MGm NGm NOm GFFm GGKm GHIm m Nm GNm IHm JGm KFm KOm MHm NHm OFm GFHm GGLm GHKm Hm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GHLm GILm GJOm GNGm HFMm HIGm HJGm HKFm HKOm HMHm HOFm IFJm m GHMm GINm GKFm GNIm HGFm HIHm HJHm HKHm HLFm HNHm HOGm IFMm m GHNm GIOm GKMm GNLm HHFm HIJm HJIm HKIm HLGm HNIm HOIm IFNm m GIFm GJHm GKNm GOFm HHGm HIKm HJJm HKJm HLIm HNJm HOLm IGFm m GIGm GJJm GKOm GONm HHHm HIMm HJKm HKKm HLJm HNKm HONm IGHm IGIm m GIHm GJLm GLIm GOOm HHIm HINm HJLm HKLm HLKm HNMm HOOm m GIJm GJMm GLKm HFGm HHJm HIOm HJMm HKMm HLLm HNNm IFFm IGKm m GIKm GJNm GLNm HFJm HHMm HJFm HJNm HKNm HLMm HNOm IFGm IGMm Im m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm IGOm IIHm IJJm ILJm INJm IOMm JGGm JHJm JIMm JJMm JLFm JMNm JMOm m IHFm IIIm IKFm ILLm INKm IONm JGJm JHKm JINm JJOm JLHm m IHGm IIJm IKIm IMHm INNm IOOm JGKm JHMm JIOm JKFm JLIm JNGm m IHKm IIKm IKJm IMIm IOFm JFIm JGMm JHOm JJFm JKGm JLLm JNHm m IHLm IILm IKKm IMMm IOGm JFLm JGNm JIFm JJGm JKIm JLMm JNIm m IHMm IINm IKLm IMNm IOHm JFMm JGOm JIIm JJHm JKJm JMIm JNKm m IIFm IJGm IKOm IMOm IOIm JFNm JHFm JIKm JJIm JKNm JMJm JNLm m IIGm IJIm ILFm INFm IOKm JGFm JHIm JILm JJJm JKOm JMMm JNMm m HKMm O (2)m Jm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm JNOm GIm HGm HOm IMm JMm KLm LKm MJm NIm OIm GFHm m Gm GJm HHm IFm IOm JNm KNm LLm MKm NJm OJm GFIm m Km GKm HIm IGm JFm KFm KOm LNm MLm NKm OLm GFJm m Lm GLm HJm IHm JGm KGm LFm LOm MMm NLm OMm GFKm m Nm GMm HKm IIm JHm KHm LGm MFm MNm NMm ONm GFLm m Om GNm HLm IJm JIm KIm LHm MGm MOm NNm OOm GFMm m GGm GOm HMm IKm JJm KJm LIm MHm NFm NOm GFFm GFNm m GHm HFm HNm ILm JKm KKm LJm MIm NGm OFm GFGm GFOm Km m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GGFm GHFm GHOm GIOm GJOm GLFm GLOm GNFm GNNm GOLm HFKm HGKm m GGGm GHGm GIGm GJFm GKFm GLGm GMFm GNGm GNOm GOMm HFLm HGLm m GGHm GHHm GIIm GJGm GKGm GLHm GMGm GNHm GOFm GONm HFMm HGMm m GGJm GHIm GIJm GJHm GKIm GLIm GMIm GNIm GOGm GOOm HFNm HGNm m GGLm GHJm GIKm GJIm GKJm GLJm GMKm GNJm GOHm HFFm HGFm HGOm m GGMm GHKm GILm GJJm GKMm GLKm GMLm GNKm GOIm HFGm HGGm HHFm m GGNm GHLm GIMm GJKm GKNm GLMm GMNm GNLm GOJm HFIm HGIm HHGm m GGOm GHMm GINm GJNm GKOm GLNm GMOm GNMm GOKm HFJm HGJm HHHm Lm m Gm Hm m Jm Km Lm Mm Nm Om GFm GGm GHm HHIm HIHm HJHm HKGm HKOm HLNm HNFm HNNm HOLm IFMm IGMm IHNm m HHKm HIKm HJIm HKHm HLFm HMGm HNGm HNOm HOMm IFOm IGNm IHOm m HHLm HILm HJJm HKIm HLGm HMHm HNHm HOFm HONm IGFm IGOm IIFm m HHMm HIMm HJKm HKJm HLHm HMIm HNIm HOGm IFFm IGGm IHFm IIGm m HHNm HINm HJMm HKKm HLIm HMJm HNJm HOHm IFHm IGHm IHGm IIHm m HHOm HIOm HJNm HKLm HLKm HMKm HNKm HOIm IFIm IGIm IHHm IIIm m HIFm HJFm HJOm HKMm HLLm HMNm HNLm HOJm IFKm IGKm IHJm IIJm m HIGm HJGm HKFm HKNm HLMm HMOm HNMm HOKm IFLm IGLm IHLm IIKm Mm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm IILm IJKm IKJm ILHm IMFm INGm IOFm IOOm JFNm JGNm JHOm JIMm m IIMm IJLm IKKm ILIm IMIm INHm IOGm JFFm JFOm JGOm JIFm JINm m IINm IJMm IKLm ILJm IMJm INIm IOHm JFHm JGFm JHGm JIGm JIOm m IIOm IJNm IKMm ILKm IMKm INJm IOJm JFIm JGGm JHHm JIHm JJFm m IJFm IJOm IKNm ILLm IMLm INKm IOKm JFJm JGJm JHIm JIIm JJGm m IJGm IKFm IKOm ILMm IMMm INLm IOLm JFKm JGKm JHJm JIJm JJHm m IJIm IKHm ILFm ILNm IMNm INMm IOMm JFLm JGLm JHKm JIKm JJIm m IJJm IKIm ILGm ILOm INFm INOm IONm JFMm JGMm JHMm JILm JJJm m HKNm (2)O m m Nm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm JJKm JKJm JLKm JMLm JNKm JOLm KFLm KGMm KHLm KIJm KJHm KKKm m JJLm JKLm JLNm JMMm JNLm JOMm KFMm KGNm KHMm KIKm KJIm KKLm m JJMm JKNm JLOm JMNm JNNm JONm KFNm KGOm KHNm KILm KJJm KKNm m JJNm JKOm JMFm JMOm JNOm JOOm KGFm KHFm KHOm KIMm KJKm KKOm m JJOm JLFm JMHm JNGm JOFm KFFm KGHm KHGm KIFm KINm KJMm KLFm m JKFm JLGm JMIm JNHm JOGm KFGm KGIm KHHm KIGm KIOm KKFm KLIm m JKGm JLHm JMJm JNIm JOJm KFHm KGJm KHIm KIHm KJFm KKGm KLJm m JKIm JLIm JMKm JNJm JOKm KFJm KGLm KHJm KIIm KJGm KKIm KLKm Om m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm KLLm KMKm KNJm KOJm LFHm LGFm LHFm LIFm LIOm LJMm LKLm LLJm m KLMm KMLm KNKm KOKm LFIm LGGm LHIm LIGm LJFm LJNm LKMm LLKm m KLNm KMNm KNLm KOLm LFJm LGHm LHJm LIIm LJGm LJOm LKNm LLLm m KLOm KMOm KNMm KOMm LFKm LGIm LHKm LIJm LJHm LKFm LKOm LLMm m KMFm KNFm KNNm KONm LFLm LGJm LHLm LIKm LJIm LKGm LLFm LLNm m KMHm KNGm KOFm KOOm LFMm LGLm LHMm LILm LJJm LKHm LLGm LLOm m KMIm KNHm KOGm LFFm LFNm LGMm LHNm LIMm LJKm LKIm LLHm LMHm m KMJm KNIm KOIm LFGm LFOm LGNm LHOm LINm LJLm LKJm LLIm LMJm m m m m m m m m m m m m m m GFm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm LMKm LNIm LOGm MFIm MGHm MHHm MIHm MJIm Im GGm GOm HOm m LMLm LNJm LOHm MFJm MGJm MHIm MIJm MJJm Jm GHm HFm IFm m LMMm LNKm LOIm MFKm MGKm MHJm MIKm MJKm Km GIm HGm IGm m LMNm LNLm LOKm MFLm MGLm MHMm MILm MJLm Lm GJm HHm IHm m LMOm LNMm LOMm MFMm MGNm MHNm MIMm MJNm Mm GKm HJm IIm m LNFm LNNm LOOm MFNm MGOm MHOm MINm MJOm Nm GLm HKm IJm m LNGm LNOm MFFm MGFm MHFm MIFm MJGm Gm Om GMm HLm IKm m LNHm LOFm MFHm MGGm MHGm MIGm MJHm Hm GFm GNm HNm ILm GGm Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm m IMm JKm KJm LIm MHm MMMm MNKm MOIm NFIm NGGm NHGm NIKm m INm JLm KKm LJm MKm MMNm MNLm MOJm NFJm NGHm NHHm NILm m IOm JMm KLm LLm MLm MMOm MNMm MOKm NFKm NGIm NHKm NIMm m JFm JNm KMm LMm MMm MNFm MNNm MOLm NFLm NGJm NHLm NINm m JGm KFm KNm LNm MNm MNGm MNOm MOMm NFMm NGMm NHMm NIOm m JHm KGm KOm LOm IHJm MNHm MOFm MONm NFNm NGNm NHOm NJFm m JIm KHm LFm MFm MNIm MOGm NFGm NFOm NGOm NIHm NJGm m JJm KIm LHm MGm MNJm MOHm NFHm NGFm NHFm NIJm NJIm HKOm O (2)m GHm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm NJJm NKIm NLLm NNIm OFGm OGHm OHKm OIKm OJKm OKOm OMJm ONMm m NJKm NKKm NLOm NNKm OFIm OGIm OHMm OILm OJMm OLGgm OMKgm ONNm m NJLm NLFm NMGm NNLm OFJm OGKm OHOm OIMm OJOm OLIm OMLgm OOFm m NJNm NLGm NMJm NNMm OFKm OGMm OIFm OINm OKFm OLKgm OMMm OOHm m NJOm NLHm NMMm NOGm OFLm OGNm OIGm OIOm OKHm OLLm OMOm OOIm m NKFm NLIm NMOm NOHm OFMm OHFm OIHm OJGm OKIm OLNm ONGm OOJm m NKGm NLJm NNFm NOIm OFNm OHGm OIIm OJIm OKMm OMGm ONKm OOKm m NKHm NLKm NNGm NONm OGFm OHIm OIJm OJJm OKNm OMHm ONLm OOLm GIm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GFFFm GFFOm GFHHm GFIIm GFJGm GFKGm GFLFm GFMFm GFNIm GFOKm GGFKm GGHIm m GFFGm GFGFm GFHIm GFIJm GFJHm GFKHm GFLGm GFMGm GFNJm GFOLm GGGGm GGHKm m GFFHgm GFGGm GFHJm GFIKm GFJJm GFKJm GFLHm GFMHm GFNKm GFOMm GGGHm GGHLm m GFFIm GFGHm GFHLm GFILm GFJKm GFKKm GFLIm GFMIm GFNLm GFONm GGGIm GGHMm m GFFJm GFGJm GFHMm GFIMm GFJLm GFKLm GFLKm GFMJm GFNMm GFOOm GGGJm GGHNm m GFFKm GFGMm GFHNm GFINm GFJMm GFKMm GFLMm GFMKm GFNNm GGFFm GGGKm GGIFm m GFFLm GFGNm GFHOm GFIOm GFJOm GFKNm GFLNm GFMMm GFNOm GGFGm GGGLm GGIGm m GFFMm GFHGm GFIFm GFJFm GFKFm GFKOm GFLOm GFMOm GFOIm GGFIm GGHGm GGIHm GJm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GGIIm GGJLm GGKNm GGMHm GGNJm GGOMm GHFNm GHHGm GHIHm GHJOm GHLOm GHNNm m GGIJm GGJNm GGKOm GGMIm GGNKm GHFGm GHFOm GHHJm GHIJm GHKFm GHMFm GHNOm m GGIKm GGJOm GGLFm GGMJm GGNMm GHFHm GHGHm GHHLm GHILm GHKGm GHMGm GHOIm m GGIMm GGKFm GGLGm GGMKm GGOFm GHFIm GHGIm GHHMm GHIOm GHKJm GHMHm GHOLm m GGINm GGKGm GGLIm GGMMm GGOGm GHFJm GHGJm GHHNm GHJHm GHKLm GHMKm GIFFm m GGJGm GGKHm GGLMm GGMOm GGOIm GHFKm GHGKm GHHOm GHJJm GHKOm GHNGm GIFGm m GGJIm GGKJm GGLNm GGNGm GGOJm GHFLm GHGLm GHIFm GHJMm GHLGm GHNHm GIFKm m GGJKm GGKKm GGMFm GGNIm GGOKm GHFMm GHHFm GHIGm GHJNm GHLIm GHNMm GIFOm GKm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GIGHm GIHMm GIJJm GILIm GIMOm GIOGm GJFMm GJHFm GJIFm GJJMm GJKLm GJNFm GJNIm m GIGIm GIIGm GIJLm GILKm GINHm GIOHm GJFOm GJHHm GJIGm GJJNm GJLFm m GIGJm GIIHm GIJMm GILNm GINIm GIOLm GJGFm GJHIm GJINm GJJOm GJMHm GJNKm m GIGLm GIIJm GIKHm GILOm GINJm GJFHm GJGGm GJHJm GJIOm GJKFm GJMIm GJNLm m GIGOm GIIKm GIKJm GIMKm GINLm GJFIm GJGHm GJHKm GJJFm GJKGm GJMJm GJNMm m GIHIm GIINm GIKKm GIMLm GINMm GJFJm GJGJm GJHLm GJJGm GJKHm GJMMm GJNNm m GIHJm GIJGm GIKMm GIMMm GINNm GJFKm GJGLm GJHNm GJJHm GJKIm GJMNm GJOGm m GIHKm GIJHm GIKNm GIMNm GIOFm GJFLm GJGOm GJHOm GJJLm GJKKm GJMOm GJOHm HLFm (2)O m GLm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GJOIm GKFKm GKGKm GKHMm GKJFm GKKHm GKLHm GKNGm GKOIm GLFLm GLHGm GLIIm GLIJm m GJOKm GKFLm GKGNm GKHNm GKJGm GKKIm GKLIm GKNHm GKOJm GLFOm GLHJm m GJOLm GKFNm GKHGm GKIFm GKJKm GKKKm GKLJm GKNIm GKOKm GLGFm GLHKm GLIKm m GJOMm GKFOm GKHHm GKIHm GKJLm GKKLm GKLKm GKNLm GKOOm GLGGm GLHMm GLILm m GJONm GKGFm GKHIm GKIIm GKJMm GKKNm GKLLm GKNNm GLFFm GLGHm GLHOm GLIMm m GKFFm GKGGm GKHJm GKIJm GKJNm GKKOm GKLMm GKOFm GLFIm GLGIm GLIFm GLIOm m GKFGm GKGHm GKHKm GKIKm GKKFm GKLFm GKLOm GKOGm GLFJm GLGKm GLIGm GLJFm m GKFIm GKGJm GKHLm GKINm GKKGm GKLGm GKMJm GKOHm GLFKm GLGNm GLIHm GLJGm GMm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GLJHm GLKHm GLLLm GLNFm GLNOm GMFGm GMGHm GMHMm GMIMm GMJOm GMKNm GMMFm GMMGm m GLJJm GLKIm GLLOm GLNGm GLOFm GMFHm GMGIm GMHNm GMINm GMKFm GMLFm m GLJKm GLKJm GLMGm GLNIm GLOGm GMFIm GMGKm GMHOm GMIOm GMKHm GMLIm GMMHm m GLJLm GLKKm GLMHm GLNJm GLOKm GMFJm GMGNm GMIGm GMJGm GMKIm GMLJm GMMIm m GLJMm GLLFm GLMIm GLNKm GLOLm GMFMm GMGOm GMIHm GMJIm GMKJm GMLKm GMMKm m GLJNm GLLGm GLMJm GLNLm GLOMm GMFNm GMHIm GMIIm GMJKm GMKKm GMLMm GMMLm m GLKFm GLLHm GLMLm GLNMm GLONm GMFOm GMHKm GMIJm GMJLm GMKLm GMLNm GMMOm m GLKGm GLLJm GLMMm GLNNm GLOOm GMGGm GMHLm GMIKm GMJNm GMKMm GMLOm GMNFm GNm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GMNGm GMOHm GNFJm GNGMm GNIJm GNJOm GNMFm GNNFm GNOHm GOFGm GOGHm GOHJm m GMNIm GMOIm GNFLm GNGOm GNIMm GNKJm GNMGm GNNGm GNOIm GOFHm GOGIm GOHKm m GMNJm GMOLm GNFNm GNHFm GNIOm GNKMm GNMHm GNNHm GNOJm GOFIm GOGJm GOHLm m GMNMm GMOMm GNGFm GNHHm GNJFm GNLGm GNMIm GNNIm GNOLm GOFKm GOGLm GOHMm m GMNNm GMONm GNGHm GNHIm GNJIm GNLJm GNMJm GNNJm GNOMm GOFLm GOGOm GOHNm m GMNOm GNFFm GNGIm GNHKm GNJKm GNLLm GNMKm GNNLm GNONm GOFNm GOHFm GOIFm m GMOFm GNFGm GNGJm GNHMm GNJLm GNLMm GNMLm GNNMm GNOOm GOFOm GOHGm GOIGm m GMOGm GNFHm GNGLm GNHOm GNJNm GNLOm GNMNm GNOFm GOFFm GOGGm GOHIm GOIHm GOm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm GOIJm GOJJm GOKKm GOMFm GONHm GOOKm HFFOm HFGNm HFIHm HFJGm HFKHm HFMGm HFMHm m GOILm GOJLm GOKLm GOMIm GONIm GOOLm HFGFm HFHHm HFIIm HFJHm HFKLm m GOIMm GOJMm GOKMm GOMKm GONJm GOOMm HFGGm HFHJm HFIJm HFJIm HFKMm HFMIm m GOINm GOJOm GOKOm GOMLm GONKm HFFHm HFGIm HFHLm HFILm HFJJm HFKNm HFMKm m GOIOm GOKFm GOLIm GOMMm GONMm HFFJm HFGJm HFHMm HFIMm HFJKm HFLGm HFMNm m GOJFm GOKGm GOLJm GOMOm GONNm HFFKm HFGKm HFHNm HFINm HFJNm HFLIm HFMOm m GOJGm GOKHm GOLMm GONFm GOOGm HFFLm HFGLm HFHOm HFIOm HFJOm HFLLm HFNFm m GOJIm GOKJm GOLOm GONGm GOOJm HFFNm HFGMm HFIGm HFJFm HFKGm HFLMm HFNHm m HLGm O (2)m HFm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm HFNIm HGFFm HGHHm HGIJm HGJOm HGKOm HGMMm HGNOm HHFHm HHGIm HHHJm HHIMm HHINm m HFNJm HGFIm HGHIm HGILm HGKFm HGLFm HGMNm HGOGm HHFIm HHGJm HHHKm m HFNMm HGFOm HGHJm HGIMm HGKGm HGLGm HGMOm HGOIm HHFJm HHGKm HHHMm HHJFm m HFOFm HGGFm HGHKm HGIOm HGKHm HGLIm HGNFm HGOKm HHFKm HHGLm HHHNm HHJJm m HFOIm HGGHm HGHLm HGJIm HGKJm HGLJm HGNGm HGOLm HHFMm HHGOm HHHOm HHJKm m HFOKm HGGJm HGIFm HGJJm HGKLm HGLKm HGNJm HGONm HHFOm HHHFm HHIGm HHJMm m HFOLm HGGLm HGIGm HGJLm HGKMm HGLLm HGNLm HGOOm HHGFm HHHGm HHIIm HHJNm m HFOOm HGGNm HGIIm HGJNm HGKNm HGLMm HGNMm HHFFm HHGHm HHHHm HHIKm HHJOm HGm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm HHKFm HHLJm HHMMm HHNNm HIFHm HIGKm HIHLm KHm GFLm GOIm HJLm IFIm m HHKIm HHLKm HHMOm HHNOm HIFIm HIGMm HIHNm LIm GGHm HFGm HJIm IFKm m HHKJm HHLNm HHNFm HHOGm HIFKm HIGOm HIIHm LMm GKKm HFIm HJNm IFLm m HHKMm HHMGm HHNGm HHOIm HIFLm HIHGm HIIIm MKm GLFm HFLm HJOgm IFOm m HHKNm HHMIm HHNHm HHOJm HIFNm HIHHm HIIKm OIm GLMm HGJm HKGm IGGm m HHLFm HHMJm HHNJm HHOLm HIGFm HIHIm Om OKm GMKm HGKm HLOm IGJm m HHLGm HHMKm HHNLm HHONm HIGHm HIHJm HFm GFIm GMMm HHLm HNGm IHFm m HHLIm HHMLm HHNMm HIFGm HIGIm HIHKm HNm GFKm GNLm HILm HOKm IHIm HHm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm IIOm INOm KMm GMJm INFm JJGm JKOm JOGm KFGm MFGm NLOm NOJm m IJHm JHHm LMm IFJm INHm JKFm JLFm JOHm KJLm MFOm NMFm NOKm m IJMm JHNm NNm ILNm IOIm JKGm JLJm JOKm KMMm MGHm NMIm OGGm m IJNm JKHm GGHm ILOm JGHm JKHm JLMm JOLm KOFm MJMm NMKm OGJm m IKHm JLOm GHGm IMFm JGIm JKIm JMOm JOMm KOGm MMKm NMLm OGLm m ILHm JMGm GHNgm IMGm JGOm JKJm JNHm JONm LGOm NKJm NMNm OHJm m IMFm GFm GJLm IMMm JINm JKKm JNIm JOOgm LMFm NLMm NNHm OHNm m INNm JOgm GKLm IMNm JJFm JKLm JNOm KFFm LMMm NLNm NOFm OJFm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm OJHm ONIm GGNOm GHKKm GHNKm GIIMm GIMFm GIKMm GKMFm HGGKm JMHm KFMm HIm m m OJLm GFGKm GGOHm GHKMm GHNLm GIJKm GIMIm GIKOm GLKOm HGJGm JNJm KFNm m OJNm GFJNm GGOOm GHKNm GHOJm GIJNm GIOOm GJLKm GLOHm GIm JOIm KGMm m OKGm GFLJm GHGFm GHLFm GHONm GIKGm GJFGm GJLLm GMIKm HKm JOJm KGOm m OLFm GFOGm GHIKm GHLJm GIFIm GIKIm GJHMm GJLOm GMKGm LGm JONm KHFm m OLMm GGFMm GHIMm GHLLm GIGNm GIKLm GJIIm GKFHm GOKNm LHm JOOm KHIm m OLOm GGGMm GHJGm GHMGm GIHHm GILHm GJIJm GKHFm HFJMm ONm KFIm KHJm m ONHm GGMGm GHKHm GHMHm GIHLm GILMm GJIMm GKLNm HFLOm JIOm KFLm KHKm m HLHm (2)O m HJm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm GHm KHLm KINm KKJm KMIm KNIm KOLm HIIMm HIJKm HIKJm HILHm HIMFm HIMNm m KHNm KIOm KKNm KMJm KNJm KONm HIINm HIJLm HIKKm HILIm HIMGm HIMOm m KHOm KJKm KKOm KMKm KNKm KOOm HIIOm HIJMm HIKLm HILJm HIMHm HINFm m KIHm KJMm KLHm KMLm KNNm LFGm HIJFm HIJNm HIKMm HILKm HIMIm HINGm m KIIm KJOm KLKm KMNm KNOm LFIm HIJGm HIKFm HIKNm HILLm HIMJm HINHm m KIJm KKGm KLOm KNFm KOFm LFJm HIJHm HIKGm HIKOm HILMm HIMKm HINIm m KIKm KKHm KMFm KNGm KOGm MIm HIJIm HIKHm HILFm HILNm HIMLm HINJm m KILm KKIm KMHm KNHm KOKm HIILm HIJJm HIKIm HILGm HILOm HIMMm HINKm GHm HKm m Gm Hm Im Jm Km Lm Mm Nm Om GFm GGm HINLm HIOLm HJFJm HJGHm HJHGm HJIGm HJJIm HJKLm HJLMm HJNIm HJOHm HJOIm m HINMm HIOMm HJFKm HJGIm HJHIm HJIHm HJJJm HJKNm HJLOm HJNJm m HINNm HIONm HJFLm HJGJm HJHJm HJIIm HJJLm HJLGm HJMGm HJNKm m HIOFm HIOOm HJFMm HJGKm HJHKm HJIJm HJJOm HJLHm HJMKm HJNLm m HIOGm HJFFm HJFNm HJGLm HJHMm HJIMm HJKFm HJLIm HJMMm HJNMm m HIOHm HJFGm HJFOm HJGMm HJHNm HJIOm HJKIm HJLJm HJMOm HJNNm m HIOJm HJFHm HJGFm HJGNm HJHOm HJJFm HJKJm HJLKm HJNFm HJOFm HIOKm HJFIm HJGGm HJGOm HJIFm HJJGm HJKKm HJLLm HJNHm HJOGm m m m m m m HLIm O m HLJm (2)m