Chapter 062. Principles of Human Genetics (Part 26)

Table 62-8 Genetic Approaches for Identifying Disease GenesMethodIndications AdvantagesandLimitationsLinkage StudiesClassical linkage analysisAnalysisofDifficulttocollect(parametric monogenic traitslarge informative pedigreesmethods) Suitable for genome scan Difficult to obtainsufficient statistical power for complex traitsControl not requiredpopulationUsefulformultifactorial disorders in isolated populationsAllele-sharingSuitableforDifficulttocollectmethods (nonparametric identification methods) susceptibility genesof sufficient number of subjects inpolygenic and multifactorial disordersAffected sib and relative pair analyses scanSuitable for genome ...
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Chapter 062. Principles of Human Genetics (Part 26) Chapter 062. Principles of Human Genetics (Part 26) Table 62-8 Genetic Approaches for Identifying Disease Genes Method Indications and Limitations Advantages Linkage Studies Classical linkage Analysis of Difficult to collectanalysis (parametric monogenic traits large informative pedigreesmethods) Suitable for genome Difficult to obtain scan sufficient statistical power for complex traits Control population not required Useful for multifactorial disorders in isolated populations Allele-sharing Suitable for Difficult to collectmethods (nonparametric identification of sufficient number of subjectsmethods) susceptibility genes in polygenic and multifactorial disorders Affected sib and Suitable for genome Difficult to obtainrelative pair analyses scan sufficient statistical power for complex traits Sib pair analysis Control population Reduced power not required if allele compared to classical frequencies are known linkage, but not sensitive to specification of genetic mode Statistical power can be increased by including parents and relatives Association Studies Case-control Suitable for Requires large samplestudies identification of size and matched control susceptibility genes in population polygenic and multifactorial disorders Linkage Suitable for testing False-positive resultsdisequilibrium specific allelic variants of in the absence of suitable known candidate loci control population Transmission Facilitated by Candidate genedisequilibrium test HapMap data, making approach does not permit to(TDT) whole-genome studies more detect novel genes and feasible pathways Whole-genome Does not necessarily Whole-genomeassociation studies need relatives association studies very expensive Linkage and Association Studies There are two primary strategies for mapping genes that cause or increasesusceptibility to human disease: (1) classic linkage can be performed based on aknown genetic model or, when the model is unknown, by studying pairs ofaffected relatives; or (2) disease genes can be mapped using allelic associationstudies (Table 62-8).