Identification of pathogenic variant enriched regions across genes and gene families.

ABSTRACT: Missense variant interpretation is challenging. Essential regions for protein function are conserved among gene-family members, and genetic variants within these regions are potentially more likely to confer risk to disease. Here, we generated 2871 gene-family protein sequence alignments involving 9990 genes and performed missense variant burden analyses to identify novel essential protein regions. We mapped 2,219,811 variants from the general population into these alignments and compared their distribution with 76,153 missense variants from patients. With this gene-family approach, we identified 465 regions enriched for patient variants spanning 41,463 amino acids in 1252 genes. As a comparison, by testing the same genes individually, we identified fewer patient variant enriched regions,

SUBMITTER: Perez-Palma E 

PROVIDER: S-EPMC6961572 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature