Epistatic selection between coding and regulatory variation in human evolution and disease.

ABSTRACT: Interaction (nonadditive effects) between genetic variants has been highlighted as an important mechanism underlying phenotypic variation, but the discovery of genetic interactions in humans has proved difficult. In this study, we show that the spectrum of variation in the human genome has been shaped by modifier effects of cis-regulatory variation on the functional impact of putatively deleterious protein-coding variants. We analyzed 1000 Genomes population-scale resequencing data from Europe (CEU [Utah residents with Northern and Western European ancestry from the CEPH collection]) and Africa (YRI [Yoruba in Ibadan, Nigeria]) together with gene expression data from arrays and RNA sequencing for the same samples. We observed an underrepresentation of derived putatively functional coding v

SUBMITTER: Lappalainen T 

PROVIDER: S-EPMC3169828 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature