Proteins linked to autosomal dominant and autosomal recessive disorders harbor characteristic rare missense mutation distribution patterns.

ABSTRACT: The role of rare missense variants in disease causation remains difficult to interpret. We explore whether the clustering pattern of rare missense variants (MAF < 0.01) in a protein is associated with mode of inheritance. Mutations in genes associated with autosomal dominant (AD) conditions are known to result in either loss or gain of function, whereas mutations in genes associated with autosomal recessive (AR) conditions invariably result in loss-of-function. Loss-of-function mutations tend to be distributed uniformly along protein sequence, whereas gain-of-function mutations tend to localize to key regions. It has not previously been ascertained whether these patterns hold in general for rare missense mutations. We consider the extent to which rare missense variants are located within a

SUBMITTER: Turner TN 

PROVIDER: S-EPMC6354780 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature