9781605351537

An Introduction to Population Genetics Theory and Applications

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  • ISBN13:

    9781605351537

  • ISBN10:

    1605351539

  • Format: Hardcover
  • Copyright: 2013-03-01
  • Publisher: Sinauer Associates is an imprint of Oxford University Press
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Summary

An Introduction to Population Genetics is intended as a text for a one-semester biology course in population genetics at the undergraduate or graduate levels. The goal of the book is to introduce both classical population genetics theory developed in terms of allele and haplotype frequencies and modern population genetics theory developed in terms of coalescent theory. Numerous applications of theory to problems that arise in the study of human and other populations are presented. Appendices provide the mathematical background necessary to understand the basic theory.

Author Biography


Rasmus Nielsen is a Professor in the Departments of Integrative Biology and Statistics at the University of California at Berkeley. He first came to Berkeley to pursue a Ph.D. in Population Genetics (with advisor, now coauthor, Montgomery Slatkin), having already earned a Masters in Biology from the University of Copenhagen. Dr. Nielsen was awarded both a Fullbright Fellowship and a Sloan Research Fellowship, and received the Ole Rmer Award and the ElitForsk Award. He edited the book Statistical Methods in Molecular Evolution (Statistics for Biology and Health) (2005). Dr. Nielsen and lab members work on statistical and computational methods and their applications in population genetics, medical genetics, molecular ecology, and molecular evolution.

Montgomery Slatkin is a Professor in the Department of Integrative Biology at the University of California at Berkeley. He earned a B.S. in Mathematics from MIT, and a Ph.D. in Applied Biomathematics from Harvard University (with George F. Carrier and William H. Bossert). Dr. Slatkin is editor of Evolution: Essays in Honour of John Maynard Smith (with P. J. Greenwood and P. H. Harvey) and Modern Developments in Theoretical Population Genetics (with M. Veuille, Oxford University Press). He was elected a member of the American Academy of Arts and Science (1997), awarded a Guggenheim Fellowship (1999-2000), and received the Sewall Wright Award of the American Society of Naturalists (2000). His research focus is population genetics and genomics, particularly of humans and archaic human relatives.

Table of Contents


Preface

Introduction


*Types of Genetic Data

*Detecting Differences in Genotype




1. Allele Frequencies, Genotype Frequencies, and Hardy-Weinberg Equilibrium


*Allele Frequencies

*Genotype Frequencies

*K-Allelic Loci

*Example: The MC1R Gene





*Hardy-Weinberg Equilibrium

*The MC1R Gene Revisited

*Box 1.1. Probability and Independence

*Box 1.2. Derivation of HWE Genotype Frequencies

*Tay-Sachs Disease





*Extensions and Generalizations of HWE

*Deviations from HWE1: Assortative Mating

*Deviations from HWE 2: Inbreeding

*Deviations from HWE3: Population Structure

*Deviations from HWE 4: Selection

*The Inbreeding Coefficient

*Testing for Deviations from HWE

*Box 1.3. The Chi-Square Test








2. Genetic Drift and Mutation


*The Wright-Fisher Model

*Genetic Drift and Expected Allele Frequencies

*Box 2.1. Expectation

*Patterns of Genetic Drift in the Wright-Fisher Model

*Effect of Population Size in the Wright-Fisher Model





*Mutation

*Effects of Mutation on Allele Frequency

*Probability of Fixation

*Species Divergence and the Rate of Substitution

*The Molecular Clock

*Dating the Human-Chimpanzee Divergence Time








3. Coalescence Theory: Relating Theory to Data


*Coalescence in a Sample of Two Chromosomes (n=2)


*Coalescence in Large Populations

*Mutation, Genetic Variability, and Population Size





*Infinite Sites Model

*The Tajima's Estimator

*The Concept of Effective Population Size

*Interpreting Estimates of θ





*The Infinite Alleles Model and Expected Heterozygosity

*The Coalescence Process in a Sample of n Individuals

*The Coalescence Tree and the tMRCA

*Total Tree Length and the Number of Segregating Sites





*The Site Frequency Spectrum (SFS)

*Tree Shape as a Function of Population Size




4. Population Subdivision


*The Wahlund Effect

*FST: Quantifying Population Subdivision

*The Wright-Fisher Model with Migration

*The Coalescence Process with Migration

*Expected Coalescence Times for n = 2

*FST and Migration Rates





*Divergence Models

*Expected Coalescence Times, Pairwise Difference and FST in Divergence Models

*Isolation by Distance








5. Inferring Population History and Demography


*Inferring Demography Using Summary Statistics

*Coalescence Simulations and Confidence Intervals

*Box 5.1. Simulating Coalescence Trees

*Estimating Evolutionary Trees

*Box 5.2. The UPGMA Method for Estimating Trees

*Gene Trees vs. Species Trees

*Interpreting Estimated Trees from Population Genetic Data





*Likelihood and the Felsenstein Equation

*MCMC and Bayesian Methods

*The Effect of Recombination

*Population Assignment, Clustering, and Admixture








6. Linkage Disequilibrium and Gene Mapping


*Linkage Disequilibrium

*Box 6.1. Coefficients of Linkage Disequilibrium

*Box 6.2. LD Coefficients for Two Diallelic Loci

*Box 6.3. r2 as a Correlation Coefficient

*Evolution of D

*Box 6.4. r2 and 2

*Box 6.5. Change in D Due to Random Mating

*Box 6.6. Recurrent Mutation Reduces D

*Two-Locus Wahlund Effect

*Box 6.7. Two-Locus Wahlund Effect





*Genealogical Interpretation of LD

*Recombination





*Association Mapping

*Box 6.8. Example of a Case-Control Test








7. Selection I


*Selection in Haploids

*Selection in Diploids

*Box 7.1. Haploid Selection

*Box 7.2. One Generation of Viability Selection

*Box 7.3. Algebraic Calculation of Allele Frequency Changes

*Box 7.4. Special Cases of Selection

*Box 7.5. Genic Selection

*Box 7.6. Heterozygote Advantage

*Box 7.7. Estimates of Selection Coefficients for the S Allele in a West African Population

*Mutation-Selection Balance

*Allelic Heterogeneity

*Fertility Selection












8. Selection in a Finite Population


*Fixation Probabilities of New Mutations

*Box 8.1. Simulating Trajectories





*Rates of Substitution of Selected Alleles

*Box 8.2. Accounting for Multiple Substitutions

*Box 8.3. Computing Synonymous and Nonsynonymous Rates





*Genetic Hitchhiking

*Selective Sweeps

*Box 8.4. Hitchhiking in a Haploid Population

*Partial Sweeps

*Associative Overdominance

*Box 8.5. Estimating the Age of a Mutation








9. The Neutral Theory and Tests of Neutrality


*The HKA Test

*The MacDonald-Kreitman (MK) Test

*The Site Frequency Spectrum (SFS)

*Tajima's D Test

*Tests Based on Genetic Differentiation among Populations

*Tests Using LD and Haplotype Structure




10. Selection II: Interaction and Conflict


*Selection on Sex Ratio

*Resolving Conflicts

*Box 10.1. The Prisoner's Dilemma





*Kin Selection

*Selfish Genes

*Meiotic Drive

*Transposons





*Species Formation




11. Quantitative Genetics


*Biometrical Analysis

*Box 11.1. Normal Distribution

*Box 11.2. Variance of the Mid-parental Value





*Breeding Value

*Quantitative Trait Loci

*Multiple Quantitative Trait Loci

*Genotype-Environment Interactions





*Mapping Quantitative Trait Loci

*Box 11.3. Mapping Alleles When Starting with Homozygous Populations








Appendix A. Basic Probability Theory
Appendix B. The Exponential Distribution and Coalescence Times
Appendix C. Maximum Likelihood and Bayesian Estimation
Appendix D. Critical Values of the Chi-square Distribution with d Degrees of Freedom
Solutions to Odd-Numbered Exercises
Glossary
Credits
Index

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