Positive epistasis between disease-causing missense mutations and silent polymorphism with effect on mRNA translation velocity.

ABSTRACT: Epistasis refers to the dependence of a mutation on other mutation(s) and the genetic context in general. In the context of human disorders, epistasis complicates the spectrum of disease symptoms and has been proposed as a major contributor to variations in disease outcome. The nonadditive relationship between mutations and the lack of complete understanding of the underlying physiological effects limit our ability to predict phenotypic outcome. Here, we report positive epistasis between intragenic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)-the gene responsible for cystic fibrosis (CF) pathology. We identified a synonymous single-nucleotide polymorphism (sSNP) that is invariant for the CFTR amino acid sequence but inverts translation speed at the affected c

SUBMITTER: Rauscher R 

PROVIDER: S-EPMC7848603 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature