Pedigree and Linkage Analysis

This chapter shows how the analysis of cosegregation in nuclear families (e.g., parents and siblings) can be used to filter genes and variants in WES/WGS studies. The family structure is recorded in PED files. The chapter begins with an explanation of the PED file format and the symbols used for describing a pedigree. Jannovar&s;s strategy for performing pedigree analysis is to first group variants according to the gene they are located in. For larger pedigrees, classical linkage analysis is more powerful because it incorporates genetic map and allele frequency information and permits variable penetrance, non-parametric analysis and formal haplotype inference. If large pedigrees are available, linkage analysis can be performed prior to exome sequencing, and the linkage interval can be used to filter the exome results. Alternatively, linkage can be performed using single-nucleotide polymorphism (SNP) genotypes extracted from exome data.