Mapping structural variants to rare disease genes using long-read whole genome sequencing and trait-relevant polygenic scores.

ABSTRACT: Recent studies have revealed the pervasive landscape of rare structural variants (rSVs) present in human genomes. rSVs can have extreme effects on the expression of proximal genes and, in a rare disease context, have been implicated in patient cases where no diagnostic single nucleotide variant (SNV) was found. Approaches for integrating rSVs to date have focused on targeted approaches in known Mendelian rare disease genes. This approach is intractable for rare diseases with many causal loci or patients with complex, multi-phenotype syndromes. We hypothesized that integrating trait-relevant polygenic scores (PGS) would provide a substantial reduction in the number of candidate disease genes in which to assess rSV effects. We further implemented a method for ranking PGS genes to define a se

SUBMITTER: LeMaster C 

PROVIDER: S-EPMC10984062 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature