Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-09

AUTHORS

Steven A McCarroll, Alan Huett, Petric Kuballa, Shannon D Chilewski, Aimee Landry, Philippe Goyette, Michael C Zody, Jennifer L Hall, Steven R Brant, Judy H Cho, Richard H Duerr, Mark S Silverberg, Kent D Taylor, John D Rioux, David Altshuler, Mark J Daly, Ramnik J Xavier

ABSTRACT

Following recent success in genome-wide association studies, a critical focus of human genetics is to understand how genetic variation at implicated loci influences cellular and disease processes. Crohn's disease (CD) is associated with SNPs around IRGM, but coding-sequence variation has been excluded as a source of this association. We identified a common, 20-kb deletion polymorphism, immediately upstream of IRGM and in perfect linkage disequilibrium (r2 = 1.0) with the most strongly CD-associated SNP, that causes IRGM to segregate in the population with two distinct upstream sequences. The deletion (CD risk) and reference (CD protective) haplotypes of IRGM showed distinct expression patterns. Manipulation of IRGM expression levels modulated cellular autophagy of internalized bacteria, a process implicated in CD. These results suggest that the CD association at IRGM arises from an alteration in IRGM regulation that affects the efficacy of autophagy and identify a common deletion polymorphism as a likely causal variant. More... »

PAGES

1107-1112

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.215

    DOI

    http://dx.doi.org/10.1038/ng.215

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1034479065

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19165925


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