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Human IRGM gene “to be or not to be”

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Abstract

The immunity-related GTPases (IRG proteins) are one of the strongest early resistance systems against intracellular pathogens. The IRG gene family contains 21 copies arranged as tandem gene clusters on two chromosomes in the C57BL/6 mouse genome but has been reduced to only two copies in humans: IRGC and IRGM. IRGC is not involved in immunity, but the human IRGM gene plays a role in autophagy-targeted destruction of Mycobacterium tuberculosis (BCG) and Salmonella typhimurium. Variant IRGM haplotypes have been associated with increased risk for Crohn’s disease and correlated with differential expression of IRGM transcripts. This article reviews in detail the studies performed on human samples, in vitro, and in sequence analyses that provide evidence for the unusual evolutionary history of the IRGM locus and the important role of the IRGM gene in autophagy and Crohn’s disease in response to pathogenesis.

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Acknowledgment

We are grateful to Jonathan C. Howard for his critical discussions and suggestions during the preparation of this manuscript, which helped us to refine our discussions. We thank Stefan Fuss for carefully editing the text, and we are also indebted to Hicham Bouabe and Can Alkan for their help and specific discussions.

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  1. Cemaletin Bekpen

    Present address: Department of Molecular Biology and Genetics, Boğaziçi University, Bebek, Istanbul, 34342, Turkey

Authors and Affiliations

  1. Department of Genome Sciences, University of Washington, Seattle, WA, USA

    Cemaletin Bekpen & Evan E. Eichler

  2. Howard Hughes Medical Institute, Seattle, WA, USA

    Cemaletin Bekpen & Evan E. Eichler

  3. Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Ramnik J. Xavier

  4. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Ramnik J. Xavier

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Bekpen, C., Xavier, R.J. & Eichler, E.E. Human IRGM gene “to be or not to be”. Semin Immunopathol 32, 437–444 (2010). https://doi.org/10.1007/s00281-010-0224-x

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