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University of Florida Thesis Or Dissertation Formatting FUNCTIONAL GENOMICS AND GENETICAL GENOMICS APPROACHES REVEAL ASSOCIATED GENES, GENE NETWORKS AND BIOLOGICAL PATHWAYS AFFECTING MEAT QUALITY IN BEEF By JOEL DAVID LEAL GUTIÉRREZ A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2019 © 2019 Joel David Leal Gutiérrez Go as far as you can see; when you get there, you’ll be able to see further Thomas Carlyle ACKNOWLEDGMENTS First and foremost, I would like to thank my advisor, Dr. Raluca Mateescu for having given this opportunity, support and guidance to me. I want to thank all the professors in my committee: Dr. Tracy Scheffler, Francisco Peñagaricano and Matias Kirst. I am especially grateful to Dr. Mauricio Elzo for providing me his continuous support. I want to show my appreciation to my friends in Gainesville: Zaira Estrada, Victor Dueñas, Angelica Sanclemente, Carlos Martinez and Matthew Morse, and my lab mates: Mesfin Gobena, Heather Hamblen, Sarah Flowers, Kaitlyn Sarlo and Eduardo Rodriguez. I also want to show my gratitude to my friends in Colombia: Paola Gomez, Lady Garzon, Paola Monserrate, Natalia Garcia, Paula Esquinas, Jaime Pulido, Jair Parales and Cesar Vargas for some very good memories. I also want to thank my master advisor, Dr. Ligia Jimenez for her support. Finally, I would like to express my deepest appreciation to my family for their unconditional support and love, and being the reason I always keep moving forward. 4 TABLE OF CONTENTS page ACKNOWLEDGMENTS .................................................................................................. 4 LIST OF TABLES ............................................................................................................ 9 LIST OF FIGURES ........................................................................................................ 11 LIST OF OBJECTS ....................................................................................................... 13 LIST OF ABBREVIATIONS ........................................................................................... 15 ABSTRACT ................................................................................................................... 17 CHAPTER 1 GENETIC BASIS OF IMPROVING THE PALATABILITY OF BEEF CATTLE: CURRENT INSIGHTS ............................................................................................ 19 Phenotypic Measures Describing Palatability of Beef ............................................. 20 Tenderness ...................................................................................................... 21 Juiciness ........................................................................................................... 22 Flavor ............................................................................................................... 23 Genetic Effects on Beef Palatability ........................................................................ 24 Heritability and Genetic Correlations ................................................................ 26 Genes Associated with Beef Palatability .......................................................... 28 Genomic regions associated with solubility and amount of connective tissue ...................................................................................................... 29 Genomic regions associated with marbling deposition .............................. 30 Genomic regions associated with proteolysis of cytoskeletal and cytoskeletal-associated proteins ............................................................. 32 Other mechanisms ..................................................................................... 38 2 ASSOCIATION OF µ-CALPAIN AND CALPASTATIN POLYMORPHISMS WITH MEAT TENDERNESS IN A BRAHMAN-ANGUS POPULATION .................. 42 Materials and Methods............................................................................................ 43 Cattle Population .............................................................................................. 43 Phenotypic Data ............................................................................................... 44 Genotyping ....................................................................................................... 44 Statistical Analysis ............................................................................................ 45 Bioinformatic Analysis ...................................................................................... 46 Associated LD-block Genotyping ..................................................................... 47 Results .................................................................................................................... 48 Evaluation of Warner-Bratzler Shear Force ...................................................... 48 5 Gene and Genotypic Frequencies .................................................................... 48 Predicted LD Blocks and Haplotypes ............................................................... 48 SNP and Haplotype Association Analysis ........................................................ 49 Bioinformatic Analysis ...................................................................................... 49 Analysis of Putative Functional SNPs .............................................................. 50 Regression Model Selection ............................................................................. 50 Discussion .............................................................................................................. 50 The µ-Calpain Gene ......................................................................................... 50 Calpastatin Gene .............................................................................................. 52 Significant Polymorphisms in the Calpastatin LD-block 3 ................................. 54 The cast5 and rs210861835 polymorphisms ............................................. 54 The rs730723459 polymorphism ................................................................ 57 3 STRUCTURAL EQUATION MODELING AND WHOLE-GENOME SCANS UNCOVER CHROMOSOME REGIONS AND ENRICHED PATHWAYS FOR CARCASS AND MEAT QUALITY IN BEEF ............................................................ 68 Materials and Methods............................................................................................ 69 Cattle Population and Phenotypic Data ............................................................ 69 Structural Equation Analysis ............................................................................. 71 Whole-Genome Scan Analysis ......................................................................... 72 Functional Annotation Clustering Analysis ....................................................... 74 Results .................................................................................................................... 74 Structural Equation Model for Carcass and Meat Quality Traits ....................... 74 Whole-Genome Scan for Carcass and Meat Quality Latent Variables ............. 75 Discussion .............................................................................................................. 75 Structural Equation Model for Carcass and Meat Quality Traits ....................... 75 Whole-Genome Scan for Carcass and Meat Quality Latent Variables ............. 76 Genomic regions associated with the carcass quality latent variable ......... 77 Genomic regions associated with the meat quality latent variable ............. 81 Genomic regions associated simultaneously with carcass and meat quality latent variables ............................................................................ 85 Genomic regions with effects on meat quality latent variable through carcass quality ........................................................................................ 88 4 GENOME WIDE ASSOCIATION AND GENE ENRICHMENT ANALYSIS REVEAL MEMBRANE ANCHORING AND STRUCTURAL PROTEINS ASSOCIATED WITH MEAT QUALITY IN BEEF ................................................... 96 Methods .................................................................................................................. 97 Cattle Population and Phenotypic Data ............................................................ 97 Genotyping and Data Quality Control. .............................................................. 99 Genome Wide Association Analysis ............................................................... 100 Gene Enrichment Analysis ............................................................................. 100 Gene Network and Candidate Genes with Multiple QTLs .............................. 102 Candidate Structural Protein Assessment of Proteolysis ............................... 103 Results .................................................................................................................. 104 6 Phenotypic Evaluation .................................................................................... 104 Genomic Regions Detected by the Genome Wide Association Analysis ....... 104 Enriched Pathways Related to Meat Quality .................................................. 104 Tissue restricted gene enrichment ........................................................... 104 DAVID functional classification analysis .................................................. 105 Gene Network and Candidate
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