Strunz, Tobias and Kellner, Martin and Kiel, Christina and Weber, Bernhard H. F. (2021) Assigning Co-Regulated Human Genes and Regulatory Gene Clusters. CELLS, 10 (9): 2395. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)Abstract
Elucidating the role of genetic variation in the regulation of gene expression is key to understanding the pathobiology of complex diseases which, in consequence, is crucial in devising targeted treatment options. Expression quantitative trait locus (eQTL) analysis correlates a genetic variant with the strength of gene expression, thus defining thousands of regulated genes in a multitude of human cell types and tissues. Some eQTL may not act independently of each other but instead may be regulated in a coordinated fashion by seemingly independent genetic variants. To address this issue, we combined the approaches of eQTL analysis and colocalization studies. Gene expression was determined in datasets comprising 49 tissues from the Genotype-Tissue Expression (GTEx) project. From about 33,000 regulated genes, over 14,000 were found to be co-regulated in pairs and were assembled across all tissues to almost 15,000 unique clusters containing up to nine regulated genes affected by the same eQTL signal. The distance of co-regulated eGenes was, on average, 112 kilobase pairs. Of 713 genes known to express clinical symptoms upon haploinsufficiency, 231 (32.4%) are part of at least one of the identified clusters. This calls for caution should treatment approaches aim at an upregulation of a haploinsufficient gene. In conclusion, we present an unbiased approach to identifying co-regulated genes in and across multiple tissues. Knowledge of such common effects is crucial to appreciate implications on biological pathways involved, specifically when a treatment option targets a co-regulated disease gene.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HOX GENES; CRISPR; TRANSCRIPTION; ACTIVATION; EXPRESSION; VARIANTS; TRAITS; expression quantitative trait loci; eQTL; colocalization; regulation of gene expression; co-regulation of gene expression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jul 2022 06:23 |
| Last Modified: | 12 Jul 2022 06:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45705 |
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