Integration of Linkage Analysis and Next-Generation Sequencing Data

Genetic mapping by linkage analysis has been for many years the first step in the identification of genes responsible for rare Mendelian disorders. When the focus of genetic research shifted toward the study of the more complex common disorders, alternative approaches such as association studies were shown to be more successful in identifying common variants of small effect that are in part responsible for susceptibility to such conditions. Recent advances in technologies that make feasible the sequencing of whole exomes or genomes have renewed interest in the identification of rare variants, which are in principle amenable to being detected by linkage analysis. As a result, linkage analysis and family based studies in general are being reexamined as an aid to filter and validate results of whole exome and whole genome sequencing experiments. This chapter will describe a few representative papers that have incorporated linkage analysis and its results in the design, execution, and interpretation of whole genome or whole exome sequencing studies.