Chromosome contacts in activated T cells identify autoimmune disease candidate genes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Oliver S. Burren, Arcadio Rubio García, Biola-Maria Javierre, Daniel B. Rainbow, Jonathan Cairns, Nicholas J. Cooper, John J. Lambourne, Ellen Schofield, Xaquin Castro Dopico, Ricardo C. Ferreira, Richard Coulson, Frances Burden, Sophia P. Rowlston, Kate Downes, Steven W. Wingett, Mattia Frontini, Willem H. Ouwehand, Peter Fraser, Mikhail Spivakov, John A. Todd, Linda S. Wicker, Antony J. Cutler, Chris Wallace

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. More... »

PAGES

165

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13059-017-1285-0

    DOI

    http://dx.doi.org/10.1186/s13059-017-1285-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1091481858

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28870212


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    574 https://www.grid.ac/institutes/grid.418195.0 schema:alternateName Babraham Institute
    575 schema:name Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, CB22 3AT, Cambridge, UK
    576 rdf:type schema:Organization
    577 https://www.grid.ac/institutes/grid.5335.0 schema:alternateName University of Cambridge
    578 schema:name Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, CB2 0PT, Cambridge, UK
    579 Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, CB2 0SP, Cambridge, UK
    580 JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, CB2 0XY, Cambridge, UK
    581 MRC Biostatistics Unit, University of Cambridge, Cambridge Institute of Public Health, Cambridge Biomedical Campus, CB2 0SR, Cambridge, UK
    582 National Health Service Blood and Transplant, Cambridge Biomedical Campus, Long Road, CB2 0PT, Cambridge, UK
    583 rdf:type schema:Organization
     




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