Complex structural variants in Mendelian disorders: identification and breakpoint resolution using short- and long-read genome sequencing.

ABSTRACT:

Background

Studies have shown that complex structural variants (cxSVs) contribute to human genomic variation and can cause Mendelian disease. We aimed to identify cxSVs relevant to Mendelian disease using short-read whole-genome sequencing (WGS), resolve the precise variant configuration and investigate possible mechanisms of cxSV formation.

Methods

We performed short-read WGS and analysis of breakpoint junctions to identify cxSVs in a cohort of 1324 undiagnosed rare disease patients. Long-read WGS and gene expression analysis were used to resolve one case.

Results

We identified three pathogenic cxSVs: a de novo duplication-inversion-inversion-deletion affecting ARID1B, a de novo deletion-inversion-duplication affecting HNRNPU and a homozygous deletion-inversion-delet

SUBMITTER: Sanchis-Juan A 

PROVIDER: S-EPMC6286558 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature