Burren, OS;
Rubio García, A;
Javierre, BM;
Rainbow, DB;
Cairns, J;
Cooper, NJ;
Lambourne, JJ;
... Wallace, C; + view all
(2017)
Chromosome contacts in activated T cells identify autoimmune disease candidate genes.
Genome Biology
, 18
, Article 165. 10.1186/s13059-017-1285-0.
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Abstract
BACKGROUND: Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4 + T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes. RESULTS: Within 4 h, activation of CD4 + T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C. By integrating promoter capture Hi-C data with genetic associations for five autoimmune diseases, we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153 kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach. CONCLUSIONS: Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.
| Type: | Article |
|---|---|
| Title: | Chromosome contacts in activated T cells identify autoimmune disease candidate genes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13059-017-1285-0 |
| Publisher version: | http://doi.org/10.1186/s13059-017-1285-0 |
| Language: | English |
| Additional information: | © The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Genetics; Genomics; Chromatin conformation; CD4+ T cells CD4+ T cell activation; Autoimmune disease; Genome-wide association studies |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10047221 |
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