Evidence for secondary-variant genetic burden and non-random distribution across biological modules in a recessive ciliopathy.

ABSTRACT: The influence of genetic background on driver mutations is well established; however, the mechanisms by which the background interacts with Mendelian loci remain unclear. We performed a systematic secondary-variant burden analysis of two independent cohorts of patients with Bardet-Biedl syndrome (BBS) with known recessive biallelic pathogenic mutations in one of 17 BBS genes for each individual. We observed a significant enrichment of trans-acting rare nonsynonymous secondary variants in patients with BBS compared with either population controls or a cohort of individuals with a non-BBS diagnosis and recessive variants in the same gene set. Strikingly, we found a significant over-representation of secondary alleles in chaperonin-encoding genes-a finding corroborated by the observation of e

SUBMITTER: Kousi M 

PROVIDER: S-EPMC8272915 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature