No preferential mode of inheritance for highly constrained genes.

ABSTRACT: Genetic constraint metrics such as the gnomAD probability of being loss-of-function (LoF) intolerant (pLI) are used to prioritize candidate genes but the mode of inheritance of highly constrained genes has never specifically been studied. We compared 605 genes with a pLI of 1 (pLI1 group) with a random sample of 635 genes from gnomAD (the random group) in terms of genetic constraint metrics, associations with Mendelian disease, modes of inheritance, and two intragenic constraint scores: the percentage of constraint coding regions (CCR) in the 99^th percentile and the gene variation intolerance rank (GeVIR). The proportion of genes associated with a Mendelian disease was 35.9% (217/605) in the pLI1 group and 19.5% (124/635) in the random group (p < 0.0001). The modes of inh

SUBMITTER: Fabre A 

PROVIDER: S-EPMC8898387 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature