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The Genetics of Human Populations


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Preface Introduction 1 The Basic Concepts of Genetics 1.1 "Cells, DNA, and Protein" 1.2 The Synthesis of Proteins and the Genetic Code 1.3 Duplication of DNA and Cell Reproduction 1.4 The Formation of Gametes: Meiosis or Reduction 1.5 Mutation and Selection 1.6 Dominance and Recessiveness: Phenotype and Genotype 1.7 The Laws of Mendelian Inheritance 1.8 Linkage and Recombination 1.9 The Gene Concept 2 Mendelian Populations 2.1 Some Basic Factors of Population Genetics 2.2 "Phenotype, Genotype, and Gene Frequencies" 2.3 Prediction of Frequencies of Genotypes under Random Mating: The Hardy-Weinberg Equilibrium 2.4 Composition of an Equilibrium Population 2.5 Extension of the Hardy-Weinberg Theorem to Mulitple Alleles and to Polyploids 2.6 Testing Equilibrium and the Meaning of Departures from It 2.7 Sex-linked Genes 3 Deleterious Mutations and the Estimation of Mutation Rates 3.1 General Charateristics of Deleterious Mutations 3.2 Models Describing the Balancing Forces of Mutation and Selection 3.3 Kinetics of the Approach to Equilibrium 3.4 Estimation of Mutation Rates 3.5 Chromosomal Aberrations 3.6 Sex-linked Genes 3.7 Parental Age and Mutation 3.8 Average Mutation Rate per Locus per Generation 4 Transient and Balanced Polymorphisms 4.1 Definition of Polymorphism: Balanced (Stable) and Transient 4.2 Opposing Forces That Produce and Maintain Polymorphism 4.3 Stability of a Polymorphism 4.4 Kinetics of the Selection Process for Transient Polymorphisms 4.5 Kinetics of the Selection Process for Balanced Polymorphisms 4.6 The Sickle-cell Polymorphism 4.7 Relationship Between the Sickle-cell Polymorphism and Malaria 4.8 Other Polymorphisms That May Be Adaptions to Malaria 4.9 The Conditions for Simultaneous Polymorphism of Three Alleles at One Locus 4.10 X-linked Polymorphisms 4.11 Other Mechanisms That Lead to Balanced Polymorphism 5 "Polymorphisms for Blood Groups, Transplatation Antigens, and Serum Proteins: Incompatibility Selection" 5.1 Polymorphisms of Blood Components 5.2 Antigens and Antibodies 5.3 Rhesus Blood Groups and Hemolytic Disease of the Newborn 5.4 ABO Blood Groups and Blood Transfusion 5.5 ABO Blood Groups and Incompatibility Selection 5.6 Associations Between ABO Blood Groups and Disease 5.7 Other Red-blood-cell Groups 5.8 The Chemistry and Genetics of Polymorphism Related to ABO 5.9 The Complex Genetics of the Rheus Blood-group System 5.10 The Genetic Basis for Histocompatibility Differences 5.11 The HL-A Polymorphism 5.12 "The Gm Polymorphism, and the Genetic Control of Antibody Structure" 6 Genetic Demography and Natural Selection 6.1 Demography and the Measurement of Fitness 6.2 Age-specific Birth and Death Rates and the Intrinsic Rate of Increase of a Population 6.3 The Life Table and Lotka's Equation for the Intrinsic Rate of Increase 6.4 The Use of r for the Measurement of Selective Differences 6.5 The Distribution of Progeny Size 6.6 The Size of Investigations Needed to Measure Selection Intensity 6.7 Evolutionary Advance and the Index of Opportunity for Selection 6.8 The Fitness Flow Sheet 6.9 Sources of Data 7 Inbreeding 7.1 Consanguinity and Inbreeding 7.2 The Inbreeding Coefficient 7.3 Consequences of Inbreeding for Mendelian Populations 7.4 Average Inbreeding in Human Populations 7.5 Consequences of Inbreeding: Genetic Loads 7.6 Analysis of Data on Inbreeding Effects on Mortality 7.7 Effects of the Inbreeding Level on Equilibrium Gene Frequencies 7.8 Consanguinity and Detrimental Recessives 7.9 Retrospective Studies on Consanguinity Effects 7.10 "The Number of Genes Determining Mental Deficiency, Deafmutism, and Blindness" 7.11 "Estimation of Overall Mutation Rates for Recessive Genes, Taking Account of Inbreeding" 8 Population Structure 8.1 Random Genetic Drift 8.2 Prediction of the Extent of Variation of Gene Frequencies After n Generations 8.3 Heterogeneity Between Populations under Hardy-Weinberg Equilibrium and Wahlunds' Formula 8.4 Equilibrium Between Drift and Linear Evolutionary Pressures 8.5 The Interaction of Drift and Selection: Some Further Considerations 8.6 The Fate fo Single Mutant Genes 8.7 The Number of Alleles That Can Be Maintained in a Finite Population 8.8 Population Effective Size 8.9 Subdivision of a Species and Models of Isolation 8.10 Demographic Data Relevant to the Analysis of Drift 8.11 Genetic Migration: the Distribution of Distance Between Birthplaces of Parent and Offspring 8.12 Analysis of Geographic Variation 8.13 Analysis of Correlation and Covariation with Distance 8.14 Migration Matrices 8.15 Predicting Drift by Computer Simulation 8.16 Drift in Time 8.17 Inbreeding and Drift 8.18 Estimation of the Expected Proportions of Consanguineous Matings 8.19 Isonymy 8.20 A Comparison and Summary of Methods of Measuring the Amount of Kinship and Ascertaining the Effect of Drift 8.21 The Problem of Isolate Size 8.22 Gene Diffusion 8.23 Gene Flow 9 "Quantitative Characters, Polygenic Inheritance, and Environmental Interactions" 9.1 The Physiology of Continuous Variation 9.2 Genetic Models of Quantitative Variation 9.3 Interaction of Genotype and Environment 9.4 The Basic Model of Polygenic Inheritance 9.5 Skin Color as an Example of Polgenic Inheritance 9.6 Partitioning the Genetic Variance in a Random-mating Population 9.7 Assortative Mating and its Effect on Quantitative Characters 9.8 Inbreeding Effects 9.9 Heritability of Threshold Characters 9.10 The Biological Basis of Twinning 9.11 The Use of Twins for the Study of Genetic Determination of Traits 9.12 The Problem of Nature vesus Nurture and the Limitations to the Concept of Heritability 9.13 The Effect of Natural Selection on Quantitative Characters 9.14 The Genetics of Schizophrenia 10 The Sexual Dimorphism 10.1 Sex Determination 10.2 The X-Chromosome Map 10.3 Sex-chromosome Abnormalities 10.4 Y-linkage and Partial Sex Linkage 10.5 Dosage Compensation and X-inactivation 10.6 The Sex Ratio 10.7 Natural Selection and the Sex Ratio 10.8 The Evolution of the Sexual Dimorphism 11 Human Evolution 11.1 Fossil Evidence on the Origin of Man 11.2 "Primates, Hominoids, and Hominids" 11.3 Paleolithic and Neolithic Man 11.4 Racial Differentiation in Man 11.5 "Measurement of Genetic Similarity and Distance Between Populations, Using Polymorphic Genes" 11.6 Analysis of Racial Differences on the Basis of Polymorphic Genes 11.7 Methods of Phylogenetic Analysis 11.8 The Frequency of Polymorphisms and Its Meanings 11.9 Molecular Evolution and Fate of Amino Acid Substitutions in Proteins 11.10 Theoretical Considerations on the Mean Time for Gene Substitution 11.11 The Relative Roles of Natural Selection and Drift in Human Evolution 12 "Eugenics, Euphenics, and Human Welfare" 12.1 The History of Eugenics and some General Problems of Its Practice 12.2 Prospects for Negative Eugenics 12.3 Eugenic Potentialities of Consanguineous and Assortative Mating 12.4 Methods of Positive Eugenics 12.5 Euphenics and Genetic Engineering 12.6 Cultural Evolution and Its Effect on Natural Selection 12.7 Other Interactions of Cultural and Biological Evolution in Man 12.8 Patterns of Fertility 12.9 Migration 12.10 Environmental Pollution and Mutagenicity 12.11 Segregation and Amalgamation 12.12 Race and Society 12.13 Changes in the Complexity of Society Appendix I Statistics and Probability I.1 Introduction I.2 Distribution I.3 Expected Values I.4 The Normal Distribution I.5 Variance I.6 Parameters I.7 Change of Scale and Location-Mean and Variance of a Function of the Original Variable I.8 Moments I.9 The Combination of Probabilities I.10 The Binomial Distribution I.11 The Poisson Distribution I.12 The Geometric Distribution I.13 The Negative Binomial Distribution I.14 The Multinomial Distribution I.15 The Gamma Distribution I.16 Distributions of Sums of Variables in Some Special Cases I.17 The Exponential Distribution I.18 Beta Distributions I.19 The Lognormal Distribution I.20 Analysis of Data I.21 Statistics and Estimation I.22 Maximum Likelihood Estimation I.23 Significance Tests and Confidence Limits I.24 Significance of the Difference Between Observed Means I.25 One-way Analysis of Variance and the F or Variance Ratio Distribution I.26 Analysis of Variance I.27 Goodness of Fit and the Chi-square Test I.28 2 x 2 Contingency Tables I.29 2 x k and 1 x k Contigency Tables I.30 Goodness of fit of the Poisson Distribution I.31 "Pairs of Measurements, Correlation, and Regression" I.32 The Bivariate Normal Distribution I.33 Multinomial Distributions I.34 Analysis of Observed Pairs of Measurements I.35 Linear Regression Analysis I.36 Intraclass Correlation Coefficient I.37 Fisher's Scoring Method for the Solution of Maximum Likelihood Equations: One Parameter I.38 Scoring for Several Parameters I.39 An Example of a Computer Program Appendix II Segregation and Linkage Analysis in Human Pedigrees and the Estimation of Gene Frequencies II.1 Pedigrees and Segregation Analysis II.2 Modes of Ascertainment II.3 Truncate Selection II.4 Single Selection II.5 Multiple Selection II.6 Sporadic Cases II.7 Inbreeding in Sporadic Cases II.8 Estimation of Prevalence with Incomplete Selection II.9 The Separation of Segregating and Nonsegregating Families with Complete Selection II.10 Incorporation of Family-size Distributions for the Estimation of Prevalence II.11 Analysis of Linkage in Human Pedigrees II.12 Linkage Analysis by Likelihood II.13 Heterogeneity of Linkage Estimates II.14 General Methods and Tables for Linkage Analysis II.15 Partial Sex Linkage II.16 Map Length and Physical Length II.17 Assignment of Genes to Chromosomes II.18 Estimation of Gene Frequencies II.19 Samples of Related Individuals Appendix III Sample Problems Literature Cited Indexes

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