Detection and analysis of complex structural variation in human genomes across populations and in brains of donors with psychiatric disorders.

ABSTRACT: Complex structural variations (cxSVs) are often overlooked in genome analyses due to detection challenges. We developed ARC-SV, a probabilistic and machine-learning-based method that enables accurate detection and reconstruction of cxSVs from standard datasets. By applying ARC-SV across 4,262 genomes representing all continental populations, we identified cxSVs as a significant source of natural human genetic variation. Rare cxSVs have a propensity to occur in neural genes and loci that underwent rapid human-specific evolution, including those regulating corticogenesis. By performing single-nucleus multiomics in postmortem brains, we discovered cxSVs associated with differential gene expression and chromatin accessibility across various brain regions and cell types. Additionally, cxSVs det

SUBMITTER: Zhou B 

PROVIDER: S-EPMC11608572 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature