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Genetic Analysis of Complex Disease
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Страница 1
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
Страница 7
Страница 8
Страница 9
Страница 10
1 Designing a Study for Identifying Genes in Complex Traits
Introduction
Components of a Disease Gene Discovery Study
Define Disease Phenotype
Clinical Definition
Determining that a Trait Has a Genetic Component
Identification of Datasets
Develop Study Design
Family‐Based Studies
Population‐Based Studies
Approaches for Gene Discovery
Analysis Genomic Analysis
Statistical Analysis
Bioinformatics
Follow‐up Variant Detection
Replication
Functional Studies
Keys to a Successful Study Foster Interaction of Necessary Expertise
Develop Careful Study Design
References
2 Basic Concepts in Genetics
Introduction
Historical Contributions Segregation and Linkage Analysis
Hardy–Weinberg Equilibrium
DNA, Genes, and Chromosomes Structure of DNA
Genes and Alleles
Genes and Chromosomes
Genes, Mitosis, and Meiosis
When Genes and Chromosomes Segregate Abnormally
Inheritance Patterns in Mendelian Disease
Autosomal Recessive
Autosomal Dominant
X‐linked Inheritance
Mitochondrial Inheritance
Y‐linked
Genetic Changes Associated with Disease/ Trait Phenotypes Mutations Versus Polymorphisms
Point Mutations
Sickle Cell Anemia
Achondroplasia
Deletion/Insertion Mutations
Duchenne and Becker Muscular Dystrophy
Cystic Fibrosis
Charcot‐Marie‐Tooth Disease
Nucleotide Repeat Disorders
Susceptibility Versus Causative Genes
Summary
References
3 Determining the Genetic Component of a Disease
Introduction
Study Design
Selecting a Study Population
Population‐Based
Clinic‐Based
Ascertainment
Single Affected Individual
Relative Pairs
Extended Families
Healthy or Unaffected Controls
Ascertainment Bias
Approaches to Determining the Genetic Component of a Disease
Co‐segregation with Chromosomal Abnormalities and Other Genetic Disorders
Familial Aggregation
Family History Approach
Example of Calculating Attributable Fraction
Correlation Coefficients
Twin and Adoption Studies
Recurrence Risk in Relatives of Affected Individuals
Heritability
Example Using Correlation Coefficients to Calculate Heritability
Segregation Analysis
Summary
References
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