| Autor: |
van Bree, Elisabeth J., Guimarães, Rita L.F.P., Lundberg, Mischa, Blujdea, Elena R., Rosenkrantz, Jimi L., White, Fred T.G., Poppinga, Josse, Ferrer-Raventós, Paula, Schneider, Anne-Fleur E., Clayton, Isabella, Haussler, David, Reinders, Marcel J.T., Holstege, Henne, Ewing, Adam D., Moses, Colette, Jacobs, Frank M.J. |
| Zdroj: |
Genome Research; 2022, Vol. 32 Issue: 4 p656-670, 15p |
| Abstrakt: |
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 BIN1and CD2APAlzheimer's disease–associated risk loci and in the BCKDKParkinson's disease–associated risk locus and assessed multiple aspects of their gene-regulatory influence in a human neuronal context. Together, this study reveals a novel layer of genetic variation in transposable elements that may contribute to identification of the structural variants that are the actual drivers of disease associations of GWAS loci. |
| Databáze: |
Supplemental Index |
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