A hidden layer of structural variation in transposable elements reveals potential genetic modifiers in human disease-risk loci.

ABSTRACT: Genome-wide association studies (GWAS) have been highly informative in discovering disease-associated loci but are not designed to capture all structural variations in the human genome. Using long-read sequencing data, we discovered widespread structural variation within SINE-VNTR-Alu (SVA) elements, a class of great ape-specific transposable elements with gene-regulatory roles, which represents a major source of structural variability in the human population. We highlight the presence of structurally variable SVAs (SV-SVAs) in neurological disease-associated loci, and we further associate SV-SVAs to disease-associated SNPs and differential gene expression using luciferase assays and expression quantitative trait loci data. Finally, we genetically deleted SV-SVAs in the BIN1

SUBMITTER: van Bree EJ 

PROVIDER: S-EPMC8997352 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature