Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance.

ABSTRACT: Genetic variants underlying life-threatening diseases, being unlikely to be transmitted to the next generation, are gradually and selectively eliminated from the population through negative selection. We study the determinants of this evolutionary process in human genes underlying monogenic diseases by comparing various negative selection scores and an integrative approach, CoNeS, at 366 loci underlying inborn errors of immunity (IEI). We find that genes underlying autosomal dominant (AD) or X-linked IEI have stronger negative selection scores than those underlying autosomal recessive (AR) IEI, whose scores are not different from those of genes not known to be disease causing. Nevertheless, genes underlying AR IEI that are lethal before reproductive maturity with complete penetrance have s

SUBMITTER: Rapaport F 

PROVIDER: S-EPMC7826345 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature