Chapter 062. Principles of Human Genetics (Part 26) Table 62-8 Genetic Approaches for Identifying Disease Genes Method Indications and Advantages Limitations Linkage Studies Classical linkage analysis (parametric Analysis of monogenic traits D ifficult to collect large informative pedigrees Suitable for genome scan Difficult to obtain sufficient statistical power for complex traits Control population not required methods) Useful for multifactorial disorders in isolated populations Allele-sharing methods (nonparametric methods) Suitable for identification of susceptibility genes in polygenic and multifactorial disorders Difficult to collect sufficient number of subjects Affected sib and relative pair analyses Suitable for genome scan Difficult to obtain sufficient statistical power for complex traits Control population not required if allele frequencies are known Reduced power compared to classical linkage, but not sensitive to specification of genetic mode Sib pair analysis Statistical power can be increased by including parents and relatives Association Studies Case-control studies Suitable for identification of susceptibility genes in polygenic and multifactorial disorders Requires large sample size and matched control population Linkage Suitable for testing False- positive results disequilibrium specific allelic variants of known candidate loci in the absence of suitable control population Transmission disequilibrium test (TDT) Facilitated by HapMap data, making whole-genome studies mor e feasible Candidate gene approach does not permit to detect novel genes and pathways Whole-genome association studies Does not necessarily need relatives Whole-genome association studies very expensive Linkage and Association Studies There are two primary strategies for mapping genes that cause or increase susceptibility to human disease: (1) classic linkage can be performed based on a known genetic model or, when the model is unknown, by studying pairs of affected relatives; or (2) disease genes can be mapped using allelic association studies (Table 62-8). . Chapter 062. Principles of Human Genetics (Part 26) Table 62-8 Genetic Approaches for Identifying Disease Genes Method. methods) Suitable for identification of susceptibility genes in polygenic and multifactorial disorders Difficult to collect sufficient number of subjects Affected sib and relative. specification of genetic mode Sib pair analysis Statistical power can be increased by including parents and relatives Association Studies Case-control studies Suitable for identification of