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Assigning Co-Regulated Human Genes and Regulatory Gene Clusters
Strunz, Tobias
, Kellner, Martin, Kiel, Christina
und Weber, Bernhard H. F.
(2021)
Assigning Co-Regulated Human Genes and Regulatory Gene Clusters.
Cells 10 (9), S. 1-13.
Veröffentlichungsdatum dieses Volltextes: 12 Jan 2022 11:55
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.51400
Zusammenfassung
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 ...
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.
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Details
| Dokumentenart | Artikel | ||||
| Titel eines Journals oder einer Zeitschrift | Cells | ||||
| Verlag: | MDPI | ||||
|---|---|---|---|---|---|
| Ort der Veröffentlichung: | BASEL | ||||
| Band: | 10 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 9 | ||||
| Seitenbereich: | S. 1-13 | ||||
| Datum | 12 September 2021 | ||||
| Institutionen | Medizin > Lehrstuhl für Humangenetik | ||||
| Identifikationsnummer |
| ||||
| Stichwörter / Keywords | HOX GENES; CRISPR; TRANSCRIPTION; ACTIVATION; EXPRESSION; VARIANTS; TRAITS; expression quantitative trait loci; eQTL; colocalization; regulation of gene expression; co-regulation of gene expression | ||||
| Dewey-Dezimal-Klassifikation | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status | Veröffentlicht | ||||
| Begutachtet | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden | Ja | ||||
| URN der UB Regensburg | urn:nbn:de:bvb:355-epub-514004 | ||||
| Dokumenten-ID | 51400 |
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