Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2012 Genome-wide prediction of breeding values and mapping of quantitative trait loci in stratified nda admixed populations Ali ShaarbafToosi Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Genetics Commons Recommended Citation ShaarbafToosi, Ali, "Genome-wide prediction of breeding values and mapping of quantitative trait loci in stratified and admixed populations" (2012). Graduate Theses and Dissertations. 12756. https://lib.dr.iastate.edu/etd/12756 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Genome-wide prediction of breeding values and mapping of quantitative trait loci in stratified and admixed populations by Ali S. Toosi A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Animal Breeding and Genetics (Quantitative Genetics) Program of Study Committee: Rohan L. Fernando, Major Professor Jack Dekkers James Reecy Alicia Carriquiry Dan Nettleton Iowa State University Ames, Iowa 2012 Copyright © Ali S. Toosi, 2012. All rights reserved. ii Tribute to my late father … To my mother … To Nahid … And To Saba and Yasmin iii TABLE OF CONTENTS LIST OF TABLES .............................................................................................................................. VIII LIST OF FIGURES ............................................................................................................................... X ACKNOWLEDGEMENTS .................................................................................................................... XII ABSTRACT .................................................................................................................................... XIV CHAPTER 1. GENERAL INTRODUCTION ..................................................................................... 1 1.1 INTRODUCTION ......................................................................................................................... 1 1.2 RESEARCH OBJECTIVES ................................................................................................................ 8 1.3 THESIS ORGANISATION ......................................................................................................... 8 1.4 LITERATURE CITED .............................................................................................................. 10 CHAPTER 2. LITERATURE REVIEW ........................................................................................... 13 2.1 LINKAGE ANALYSIS ................................................................................................................... 13 2.1.1 LA of complex traits ................................................................................................................................. 14 2.1.2 LA mapping resolution ............................................................................................................................ 15 2.2 POPULATION-BASED ASSOCIATION STUDY .................................................................................... 17 2.2.1 Linkage disequilibrium ............................................................................................................................ 18 2.2.2 Measures of LD ........................................................................................................................................ 19 2.2.3 Linkage, LD and Hardy- Weinberg disequilibrium ................................................................................... 20 2.3 FACTORS AFFECTING LD ........................................................................................................... 21 2.3.1 Mutation ................................................................................................................................................. 22 2.3.2 Selection .................................................................................................................................................. 22 2.3.3 Random genetic drift ............................................................................................................................... 23 2.3.4 Non-random mating ................................................................................................................................ 24 2.4 POPULATION STRATIFICATION .................................................................................................... 25 2.4.1 Measures of PS ........................................................................................................................................ 26 iv 2.4.2 Impact of PS on statistical inferences in population genetics ................................................................. 28 2.4.3 Population admixture .............................................................................................................................. 31 2.4.4 Difference between PS and population admixture ................................................................................. 32 2.4.5 Confounding due to PS and admixture ................................................................................................... 33 2.5 TESTS OF GENETIC ASSOCIATIONS IN PBA STUDIES ........................................................................ 36 2.5.1 Tests of independence or contingency tables for binomial traits ........................................................... 37 Pearson’s χ2-test .............................................................................................................................................. 37 2.5.2 Alleles test ............................................................................................................................................... 38 2.5.3 Fisher’s exact test .................................................................................................................................... 38 2.5.4 Cochran-Armitage trend test ................................................................................................................. 39 2.5.5 Log-Likelihood ratio test .......................................................................................................................... 40 2.5.6 Test of hypothesis of no association in the presence of PS .................................................................... 40 2.5.7 Tests of associations for quantitative traits ............................................................................................ 42 2.5.8 M-sample and non-parametric tests of association for a quantitative trait ........................................... 42 2.5.9 Generalized linear model ........................................................................................................................ 43 2.5.10 Logistic regression ................................................................................................................................. 44 2.6 ANALYTICAL CHALLENGES OF HIGH-DIMENSIONAL GWAS DATA ...................................................... 46 2.6.1 Control of false-positives in GWAS .......................................................................................................... 46 2.6.1.1 Family-wise error rate .......................................................................................................................... 47 2.6.1.2 False discovery rate .............................................................................................................................. 47 2.6.1.3 Bonferroni correction for multiple comparisons ................................................................................. 49 2.6.1.4 Effective number of tests ..................................................................................................................... 49 2.6.2 Model selection in GWAS ........................................................................................................................ 51 2.7 LITERATURE CITED .............................................................................................................. 52 2.8 FIGURES ................................................................................................................................. 59 2.9 TABLES .................................................................................................................................. 63 CHAPTER 3. GENOMIC SELECTION IN ADMIXED AND CROSSBRED POPULATIONS ............... 65 v 3.1 SUMMARY ............................................................................................................................. 65 3.2 INTRODUCTION ....................................................................................................................... 66 3.3 MATERIALS AND METHODS ....................................................................................................... 67 3.3.1 Population ............................................................................................................................................... 68 3.3.2 Genome