Calculating the statistical significance of rare variants causal for Mendelian and complex disorders.

ABSTRACT:

Background

With the expanding use of next-gen sequencing (NGS) to diagnose the thousands of rare Mendelian genetic diseases, it is critical to be able to interpret individual DNA variation. To calculate the significance of finding a rare protein-altering variant in a given gene, one must know the frequency of seeing a variant in the general population that is at least as damaging as the variant in question.

Methods

We developed a general method to better interpret the likelihood that a rare variant is disease causing if observed in a given gene or genic region mapping to a described protein domain, using genome-wide information from a large control sample. Based on data from 2504 individuals in the 1000 Genomes Project dataset, we calculated the number of individuals who hav

SUBMITTER: Rao AR 

PROVIDER: S-EPMC6001062 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature