1;Preface and Introduction;5 2;Contents;10 3;Population Genetics;14 3.1;1 Introduction;14 3.2;2 Within-Population Analyses;15 3.2.1;2.1 Genotype and Allele Frequencies;15 3.2.2;2.2 Maximum Likelihood Estimation;16 3.2.3;2.3 Inbreeding Coefficient;17 3.2.4;2.4 Testing for Hardy-Weinberg Equilibrium;19 3.2.5;2.5 Linkage Disequilibrium;21 3.2.6;2.6 Composite Linkage Disequilibrium;22 3.2.7;2.7 Testing for Linkage Equilibrium;23 3.2.8;2.8 Application to Data;24 3.3;3 Between-Population and Analyses;29 3.3.1;3.1 F-statistics;29 3.3.2;3.2 Application to Data;33 3.4;4 Discussion;35 3.5;5 Web Resources;35 3.6;References;36 4;Haplotype Structure;37 4.1;1 Population Haplotype Structure;37 4.1.1;1.1 Haplotype Block Structure in Human Populations;37 4.1.2;1.2 Wright-Fisher Model;38 4.1.3;1.3 Coalescent Theory;40 4.2;2 Public Genotype/Haplotype Databases;42 4.2.1;2.1 International HapMap Project;43 4.2.1.1;Download Genotype Data from HapMap;44 4.2.2;2.2 The HapMap ENCODE Resequencingand Genotyping Project;45 4.2.2.1;2.2.1 Download ENCODE Genotype Data;46 4.2.3;2.3 Haplotype Simulation;46 4.3;3 Haploview;48 4.3.1;3.1 What is Haploview?;48 4.3.2;3.2 How to Download and Install Haploview;48 4.3.3;3.3 How to Run Haploview;49 4.3.3.1;3.3.1 How to Use HapMap Data in Haploview;49 4.3.3.2;3.3.2 How to Use Non-HapMap Genotype Data in Haploview;50 4.4;4 Haplotype Inference Methods;53 4.4.1;4.1 Clark's Algorithm;54 4.4.1.1;4.1.1 Software Usage;55 4.4.2;4.2 PHASE;58 4.4.2.1;4.2.1 PHASE Algorithm;59 4.4.2.2;4.2.2 Software Usage;60 4.4.3;4.3 HAPLOTYPER;65 4.4.3.1;4.3.1 Bayesian Model;65 4.4.3.2;4.3.2 Partition-Ligation (PL);66 4.4.3.3;4.3.3 Software Usage;68 4.4.4;4.4 CHB;70 4.4.4.1;4.4.1 CHB Model;70 4.4.4.2;4.4.2 MCMC Sampling and Convergence;72 4.4.4.3;4.4.3 Software Usage;73 4.4.5;4.5 Comparison of Phasing Results;76 4.5;5 Estimation of Recombination Rate;76 4.5.1;5.1 LDhat;77 4.5.1.1;5.1.1 Composite Likelihood Estimation of ;77 4.5.1.2;5.1.2 Likelihood Permutation Test;78 4.5.1.3;5.1.3 Software Usage;79 4.5.2;5.2 HOTSPOTTER;83 4.5.2.1;5.2.1 PAC Model;83 4.5.2.2;5.2.2 Computing the Conditional Distribution ;85 4.5.2.3;5.2.3 Software Usage;86 4.6;Summary;88 4.7;Web Resources;89 4.8;References;89 5;Linkage Analysis of Qualitative Traits;92 5.1;1 Introduction;92 5.2;2 Model-Based Linkage Analysis;93 5.2.1;2.1 Phase-Known Pedigrees;93 5.2.2;2.2 Phase-Unknown Pedigrees;96 5.2.3;2.3 Linkage Analysis in General Case;98 5.2.4;2.4 Elston-Stewart Algorithm;99 5.3;3 Model-Free Linkage Analysis;101 5.3.1;3.1 Fundamental Principle of Model-Free Linkage Analysis;101 5.3.2;3.2 Measure of Genetic Similarity;102 5.3.3;3.3 Model-Free Linkage Analysis for Affected Sib Pairs;103 5.3.4;3.4 Multipoint Analysis for Affected Sib Pairs;106 5.3.5;3.5 Model-Free Linkage Analysis for General Pedigrees;108 5.3.5.1;3.5.1 Inheritance Vector;108 5.3.5.2;3.5.2 NPL Score When the Inheritance Vector Is Known;109 5.3.5.3;3.5.3 NPL Score When the Inheritance Vector Is Uncertain;110 5.3.6;3.6 Lander-Green Algorithm;111 5.4;4 Practical Examples;113 5.5;5 Identifying SNPs Responsible for a Linkage Signal;117 5.5.1;5.1 Assumptions and Definitions;117 5.5.2;5.2 Conditional Probability of Marker Data Given ASP;118 5.5.3;5.3 Relationship Between Disease Locus and Candidate SNP;119 5.5.4;5.4 Hypothesis Testing;120 5.5.5;5.5 Extension to Sibship Data and Nuclear Families;122 5.5.6;5.6 Summary;124 5.6;6 Comparison of Model-Based and Model-Free Linkage Analysis Methods;124 5.6.1;6.1 Software Packages for Linkage Analysis;126 5.7;Web Resources;126 5.8;References;127 6;Linkage Analysis of Quantitative Traits;130 6.1;1 Introduction and Description of Data;130 6.2;2 Methods;132 6.2.1;2.1 Classical Model-Based Linkage Analysis;134 6.2.2;2.2 Model-Free Haseman-Elston Regression Approach;138 6.2.3;2.3 Variance-Components Approaches;139 6.2.4;2.4 Model-Free Variance Regression;145 6.2.5;2.5 Multivariate Models;147 6.2.6;2.6 Joint Linkage and Association Analysis;149 6.3;3 Discussion;149 6.4;4 Web Resourc