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Summary of Commonly Used Notation | |
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Overview of Genetic Epidemiology | |
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The Process of Genetic Epidemiology | |
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Descriptive Epidemiology and Hypothesis Generation | |
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Familial Aggregation | |
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Segregation Analysis | |
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Linkage Analysis | |
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Fine Mapping and Cloning | |
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Candidate Gene Association Studies | |
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Characterizing the Effects of Cloned Genes | |
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Conclusions | |
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Basic Concepts of Molecular Genetics | |
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Chromosomes | |
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Cell Division | |
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Cell Cycle | |
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Mitosis | |
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Meiosis | |
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Genetic Recombination | |
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Meiotic Recombination | |
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Mitotic Recombination | |
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DNA | |
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Gene Expression | |
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Transcription | |
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RNA Processing | |
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Translation | |
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Post-Translational Modification | |
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DNA Polymorphism | |
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Conclusions | |
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Principles of Mendelian Inheritance | |
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Basic Concepts | |
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Mendelian Inheritance at a Single Locus | |
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Classical Autosomal Dominant Inheritance | |
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Classical Autosomal Recessive Inheritance | |
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Classical X-Linked Inheritance | |
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Multiallelic Loci | |
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Mendelian Inheritance at Two Loci | |
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Conclusions | |
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Basic Epidemiologic and Statistical Principles | |
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Basic Probability Theory | |
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Basic Epidemiologic Principles | |
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Study Designs | |
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Measures of Disease Frequency and Association | |
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Interpretation of Epidemiologic Associations | |
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Maximum Likelihood | |
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Generalized Estimating Equations | |
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Markov Chain Monte Carlo Methods | |
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Randomization Procedures | |
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Conclusions | |
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Familial Aggregation | |
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Genetic Relationships and Gene Identity | |
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Formal Derivation of [phi] and [Delta] | |
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Familial Correlations of Continuous Phenotypes | |
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Familial Risk of Disease | |
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The Concept of Familial Risk | |
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Design Principles | |
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Analytical Approaches | |
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Other Designs | |
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Randomization Tests of Familial Clustering | |
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Twin Studies | |
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Adoption Studies | |
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Approaches to Dependent Data | |
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Genetic Models | |
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Regressive Models | |
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Frailty Models | |
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Generalized Estimating Equations | |
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Conclusions | |
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Segregation Analysis | |
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Design Issues | |
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Ascertainment of Families | |
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Sequential Sampling | |
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Classical Methods for Sibships | |
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Ascertainment Correction | |
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Likelihood Methods for Pedigree Analysis | |
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General Model | |
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Polygenic and Mixed Models | |
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Penetrance Models | |
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The Elston-Stewart Peeling Algorithm | |
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Hypothesis Testing | |
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Alternative Methods | |
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Gibbs Sampling | |
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Generalized Estimating Equations | |
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Applications to Breast Cancer | |
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Conclusions | |
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Linkage Analysis | |
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Recombination and Map Functions | |
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Direct Counting Methods | |
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Relative Pair Methods | |
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Identity by State and by Descent | |
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Affected Sib Pair Methods | |
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Affected Relative Pair Methods | |
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Sib Pair Methods for Quantitative Traits | |
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Generalized Estimating Equation Methods | |
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Lod Score Methods | |
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Two-Point Linkage | |
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Joint Segregation and Linkage Analysis and the Mod Score | |
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Multipoint Linkage and Ordering Loci | |
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Genome-Wide Scans | |
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Genetic Heterogeneity | |
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Gibbs Sampling Methods | |
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Design Issues | |
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Power and Sample Size | |
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Selection Bias and Misspecification | |
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Fine Mapping and Cloning of BRCA1 | |
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Conclusions | |
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Principles of Population Genetics | |
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Distribution of Genes at a Single Locus | |
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Hardy-Weinberg Equilibrium in Large Populations | |
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Genetic Drift in Finite Populations | |
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Effects of Mutation and Selection | |
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Distribution of Genes at Two Loci | |
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Origins of Linkage Disequilibrium | |
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Decay of Linkage Disequilibrium | |
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Estimation of Linkage Disequilibrium | |
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Evolution of Haplotypes | |
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Ancestral Inference | |
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Coalescent Trees | |
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Ancestral Recombination Graphs | |
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Conclusions | |
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Testing Candidate Gene Associations | |
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Distributions of Genes in Affected and Unaffected Individuals | |
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Homogeneous Populations | |
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Ethnically Stratified Populations | |
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Families | |
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Design Options for Association Studies | |
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Cohort Study Designs | |
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Case-Control Designs | |
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Parental Controls and the Transmission/Disequilibrium Test | |
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Family-Based Association Tests | |
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Quantitative Traits | |
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Conclusions | |
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Linkage Disequilibrium Mapping | |
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Recently Admixed Populations | |
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Isolated Populations | |
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Empiric Methods for Estimating the Location of a Disease Gene or Mutation | |
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Haplotype Sharing Methods | |
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Parametric Methods Based on the Coalescent | |
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How Much Linkage Disequilibrium Is There in the Human Genome? | |
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Haplotype Block Structure | |
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Conclusions | |
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Gene Characterization | |
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Estimation of Genetic Risks | |
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Cohort and Case-Control Designs Using Unrelated Subjects | |
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Familial Cohort Study Designs | |
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Multistage Sampling and Countermatching | |
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Relative Efficiency of the Alternative Designs | |
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Gene-Environment and Gene-Gene Interactions | |
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Case-Control Designs | |
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Case-Only Studies | |
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Case-Parent Trios | |
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Gene-Environment Interactions for Breast Cancer | |
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Relative Efficiency of Alternative Designs for Interaction Effects | |
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Estimation of Gene Frequencies and Carrier Probabilities | |
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Searching for Additional Genes | |
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Conclusions | |
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Tying It All Together: the Genetic Epidemiology of Colorectal Cancer | |
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History, Descriptive Epidemiology, and Familiality | |
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Mechanistic Hypotheses | |
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Models of Carcinogenesis | |
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Cancer Genes | |
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Genomic Instability | |
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Familial Cancer Syndromes | |
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Familial Adenomatous Polyposis | |
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Hereditary Nonpolyposis Colorectal Cancer | |
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Sporadic Cancers | |
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Genetic Alterations in Colorectal Cancer | |
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Pathways: Suppressor and Mutator | |
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Metabolic Pathways | |
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The Relationship Between Polyps and Colorectal Cancer | |
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Discovery of Novel Colorectal Cancer Genes | |
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Implications for Clinical Management | |
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The Future | |
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Genome-Wide Scans for Association and Interactions | |
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Gene Expression Assays | |
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DNA Methylation and Loss of Imprinting | |
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Conclusions | |
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Glossary | |
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References | |
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Index | |