De novo and inherited variants in coding and regulatory regions in genetic cardiomyopathies.

ABSTRACT:

Background

Cardiomyopathies are a leading cause of progressive heart failure and sudden cardiac death; however, their genetic aetiology remains poorly understood. We hypothesised that variants in noncoding regulatory regions and oligogenic inheritance mechanisms may help close the diagnostic gap.

Methods

We first analysed whole-genome sequencing data of 143 parent-offspring trios from Genomics England 100,000 Genomes Project. We used gene panel testing and a phenotype-based, variant prioritisation framework called Exomiser to identify candidate genes in trios. To assess the contribution of noncoding DNVs to cardiomyopathies, we intersected DNVs with open chromatin sequences from single-cell ATAC-seq data of cardiomyocytes. We also performed a case-control analysis in an exom

SUBMITTER: Vadgama N 

PROVIDER: S-EPMC9647983 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature