Improved Pathogenic Variant Localization via a Hierarchical Model of Sub-regional Intolerance.

ABSTRACT: Different parts of a gene can be of differential importance to development and health. This regional heterogeneity is also apparent in the distribution of disease-associated mutations, which often cluster in particular regions of disease-associated genes. The ability to precisely estimate functionally important sub-regions of genes will be key in correctly deciphering relationships between genetic variation and disease. Previous methods have had some success using standing human variation to characterize this variability in importance by measuring sub-regional intolerance, i.e., the depletion in functional variation from expectation within a given region of a gene. However, the ability to precisely estimate local intolerance was restricted by the fact that only information within a given s

SUBMITTER: Hayeck TJ 

PROVIDER: S-EPMC6369453 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature