Cardiac structural and sarcomere genes associated with cardiomyopathy exhibit marked intolerance of genetic variation.

ABSTRACT:

Background

The clinical significance of variants in genes associated with inherited cardiomyopathies can be difficult to determine because of uncertainty regarding population genetic variation and a surprising amount of tolerance of the genome even to loss-of-function variants. We hypothesized that genes associated with cardiomyopathy might be particularly resistant to the accumulation of genetic variation.

Methods and results

We analyzed the rates of single nucleotide genetic variation in all known genes from the exomes of >5000 individuals from the National Heart, Lung, and Blood Institute's Exome Sequencing Project, as well as the rates of structural variation from the Database of Genomic Variants. Most variants were rare, with over half unique to 1 individual. Cardiomyop

SUBMITTER: Pan S 

PROVIDER: S-EPMC3526690 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature