Identification of Disease Genes in Genetic Isolates

Genetic isolates represent exceptional resources in the identification of disease loci. Not only have specific monogenic diseases become enriched and families frequent enough to be utilized in linkage analyses, but also the vast majority of patients carry the same mutation and share identical chromosomal haplotypes at significant distances. Additionally, regional isolates often reveal an increased prevalence of common polygenic diseases, and a hypothesis that selected predisposing genes can be efficiently identified due to a restricted number of ancestor mutations seems relevant. The current genome map with highly informative markers provides the basic tools for a genome-wide random search of disease loci. Special strategies including maximal utilization of linkage disequilibrium and scanning for shared chromosomal regions can be adapted in isolated populations, and this should greatly enhance the efficiency of locus identification even in complex human diseases.