Relationship between Deleterious Variation, Genomic Autozygosity, and Disease Risk: Insights from The 1000 Genomes Project

Genomic regions of autozygosity (ROAs) represent segments of individual genomes that are homozygous for haplotypes inherited identical-by-descent (IBD) from a common ancestor. ROAs are nonuniformly distributed across the genome, and increased ROA levels are a reported risk factor for numerous complex diseases. Previously, we hypothesized that long ROAs are enriched for deleterious homozygotes as a result of young haplotypes with recent deleterious mutations —relatively untouched by purifying selection—being paired IBD as a consequence of recent parental relatedness, a pattern supported by ROA and whole-exome sequence data on 27 individuals.

Source: The American Journal of Human Genetics - March 15, 2018 Category: Genetics & Stem Cells Authors: Trevor J. Pemberton, Zachary A. Szpiech Tags: Article Source Type: research