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Genomic Analysis of Divergently Selected Experimental Lines in Rabbits

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Genomic Analysis of Divergently Selected Experimental Lines in Rabbits GENOMIC ANALYSIS OF DIVERGENTLY SELECTED EXPERIMENTAL LINES IN RABBITS Ph.D. Thesis by Bolívar Samuel Sosa Madrid Supervisors: Prof. Dr. Noelia Ibáñez Escriche Prof. Dr. Agustín Blasco Mateu Institute for Animal Science and Technology Universitat Politècnica de València València, 23th March 2020 GENOMIC ANALYSIS OF DIVERGENTLY SELECTED EXPERIMENTAL LINES IN RABBITS This thesis has been submitted in fulfilment of the requirements for the degree of Doctor with International Mention at the Universitat Politècnica de València. Esta tesis ha sido escrita y presentada como uno de los requisitos para optar al grado de Doctor con Mención Internacional por la Universitat Politècnica de València. By Bolívar Samuel Sosa Madrid _________________________________ Thesis Supervisors Prof. Dr. Noelia Ibáñez Escriche Prof. Dr. Agustín Blasco Mateu _________________________________ _________________________________ València, 23th March 2020 One is all, All is one FULLMETAL ALCHEMIST: BROTHERHOOD ACKNNOWLEDGEMENTS Yo agradezco a “DIOS” y a mi familia, quienes han sido un apoyo fundamental durante el doctorado. “DIOS”, tú me ayudaste a tomar la decisión de estudiar en el extranjero y tú has guiado mis pasos principalmente en los momentos difíciles. Mamá, Papá, “Salo” y “Gwendo”, gracias por recordarme siempre de dónde vengo, lo que valgo y lo que es importante en la vida. Yo estoy orgulloso de ser panameño, de ustedes, de nuestra cultura, costumbres e idioma. Panamá es un país pequeño lleno de personas que tienen un corazón “sólido” y “sabrosón”. También, quiero agradecer al grupo de mejora genética animal de la UPV, a los investigadores principales: María Antonia, Pilar, Agustín y Noelia, por todas sus enseñanzas. Gracias a Agustín por todo durante este tiempo de mi doctorado. Un especial gracias a Noelia, por el tiempo que dedicaste a enseñarme genómica estadística; realmente aprecio todo lo que has hecho por mí a nivel personal. Gracias a todos mis compañeros del Instituto de Ciencia y Tecnología Animal. Un millón de gracias a los compañeros de genética, Marina Martínez, Agostina, Cristina, “Mafe”, Enrico, David, Ana y los demás, quienes me acompañaron en estos últimos cuatro años. También quiero agradecer a los compañeros del grupo de acuicultura, Víctor “El Pastor”, German, Guillem, Miriam y los demás. También gracias Richard, Ximo y Andrea por las graciosas conversaciones. Un especial gracias a Federico, Verónica, Marina Morini, Antonella, Ilaria y Rosalia por su trabajo en este experimento; especialmente a Marina que me acompañó en el arduo trabajo durante 5 meses, y estuvo presente cuando proclame mi frase célebre “Que asco de vida”. También quiero agradecer a John Hickey y su grupo, especialmente a Roger y Mara, el tiempo dedicado a mi formación en mi primera estancia en Edinburgh. Para mi es y será un recuerdo especial. A Chris Haley y su grupo, en especial a Pau, Yanni, Charlie y Carmen, un millón de gracias, ya que con ustedes aprendí mucho de GWAS y el trabajo grupal, lo cual superó mis expectativas. Gracias a Luis Varona por enseñarme sobre huellas de selección y mostrarme qué tan genial puede ser Zaragoza. A “Froy”, Maru, Leonela y los demás amigos de Panamá, gracias por su apoyo en los últimos cuatro años. A Jeffry, Judith, Latifa y Kenza, un millón de gracias, ya que ustedes fueron un pilar esencial para continuar realizando el doctorado. A los amigos que conocí en Edinburgh, Piotr, Dariuz, Alberto, Yuyao y Liam, mil gracias, conocerlos me ayudo a ser feliz durante mi estancia en esa hermoso lugar que es Scotland. Un especial gracias a José “El Duque” Medina, tu amistad fue esencial para terminar la tesis este último año. Supongo que no molaba estar más de 10 minutos escuchándome hablar de genética, pero admítelo a veces era interesante. Gracias a Andrea y "Duque por la portada. Gracias a todos los amigos que tengo alrededor del mundo y a los que he olvidado mencionar. En fin, esta tesis se la dedico a “DIOS”, a mi familia y a mis amigos cercanos. I In English: I thank GOD and my family, who have been an essential support during the doctorate. GOD, you helped me take the decision of studying abroad and you have guided my steps mainly in difficult times. I would like to thank Mom, Dad, "Salo" and "Gwendo" for always reminding me where I came from, the worth of myself and what is important in life. I am so proud to be Panamanian, of my family, of our culture, customs and language. Panama is a small country full of people who have a "solid" and "sabrosón" heart. I thank to the Group of Animal Breeding from the Polytechnic University of Valencia, thanks to the main researchers: Maria Antonia, Pilar, Agustín and Noelia for their teaching. I must express my very profound gratitude to Noelia for your patience to teach me quantitative genetics and genomics. I know it was not easy, and I really appreciate everything you have done for me. Thanks to all my colleagues from the Institute for Animal Science and Technology. Thanks a million to fellows of the Group of Animal Breeding, Marina Martínez, Agostina, Cristina, "Mafe", Enrico, David, Ana and other fellows. I am also thankful to the colleagues of the Aquaculture Group, Victor “El Pastor”, German, Guillem, Miriam and the others. I would also like to thank Richard, Ximo and Andrea for the funny conversations. I must express a special thanks to Federico, Veronica, Marina Morini, Antonella, Ilaria and Rosalia, for working with me in the experiments at the rabbit farm and the meat lab; especially to Marina, my principal workmate over tough five months. You were present when I said my famous phrase “How disgusting my life”. I will not forget it. I would like to thank John Hickey and your group, particularly to Roger and Mara, for your time invested in my learning during my first stay in Edinburgh. That time was and will be a special memory for me. Thanks to Chris Haley and your group, particularly to Pau, Yanni, Charlie and Carmen, thanks a million, since I learnt with you a lot of GWAS and work as a team. That stay exceeded my expectation. I would like to thank Luis Varona for teaching methods of selection signatures, and also, for showing me the phenomenal Zaragoza. Thanks to “Froy”, Maru, Leonela and other friends in Panama for your support in the last four years. To Jeffry, Judith, Latifa and Kenza, thanks a million, since you were an essential piece to keep going with my doctorate. Thanks to my friends that I knew in Edinburgh: Piotr, Dariuz, Alberto, Yuyao y Liam, thanks a million, I was happy with you during my long stay in beautiful Scotland. I would like to express a special thanks to José “El Duque” Medina, your friendship was crucial in the last year of my thesis. I suppose that it is not nice listening to me talk about genetics over 10 minutes. Thanks to my friends around the world and those friends that I have forgotten. Finally, this thesis is dedicated to GOD, my family and close friends. II CONTENTS ACKNNOWLEDGEMENTS .......................................................................... I CONTENTS ............................................................................................ III LIST OF FIGURES ................................................................................. VII LIST OF TABLES .................................................................................... IX LIST OF ABBREVIATIONS ...................................................................... XI ABSTRACT ............................................................................................... 1 RESUMEN ................................................................................................ 3 RESUM .................................................................................................... 7 RÉSUMÉ .................................................................................................. 9 CHAPTER ONE ....................................................................................... 13 1. GENERAL INTRODUCTION ............................................................... 13 1.1. RABBIT PRODUCTION AND BREEDING ...................................................... 13 1.1.1. Overview........................................................................................ 13 1.1.2. Traits of interest in rabbit production ............................................. 13 1.1.3. Relationship between growth, meat and litter size traits ............... 14 1.2. RABBITS AS ANIMAL EXPERIMENTAL MODEL ............................................. 16 1.3. DIVERGENT SELECTION EXPERIMENTS .................................................... 16 1.4. MOLECULAR GENETICS FOR UNCOVERING THE IMPORTANCE OF GENOMICS IN RABBIT ............................................................................................... 17 1.4.1. Genome wide association study .................................................... 19 1.4.1.1. Previous to GWAS: genetic markers and genomic analyses . 19 1.4.1.2. Methods and strategies ....................................................... 20 Designing association studies ..................................................... 21 Frequentist inference .................................................................. 24 Bayesian inference ...................................................................... 28 1.4.2. Genome scan study ....................................................................... 33 1.4.2.1. Methods of selection signatures .......................................... 33 Differentiation amongst populations ..........................................
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