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

ABSTRACT: 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. Here, we significantly bolster support for our hypothesis and expand upon our original analyses using ROA and whole-genome sequence data on 2,436 indivi

SUBMITTER: Pemberton TJ 

PROVIDER: S-EPMC5985279 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature