Human IRGM gene "to be or not to be"

被引：34
作者：
Bekpen, Cemaletin [4 ,5 ]
Xavier, Ramnik J. [1 ,2 ,3 ]
Eichler, Evan E. [4 ,5 ]
机构：
[1] Broad Inst MIT & Harvard, Cambridge, MA USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA
[4] Howard Hughes Med Inst, Seattle, WA USA
[5] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
来源：
SEMINARS IN IMMUNOPATHOLOGY | 2010年 / 32卷 / 04期
关键词：
Human IRGM gene; IRG gene family; Autophagy; Crohn's disease; Innate immunity; Genome-wide association studies; Evolution of IRGM; Death and resurrection of a gene; CROHNS-DISEASE SUSCEPTIBILITY; GENOME-WIDE ASSOCIATION; IFN-GAMMA; ENDOGENOUS RETROVIRUS; TOXOPLASMA-GONDII; P47; GTPASES; INTRACELLULAR PATHOGENS; EVOLUTIONARY HISTORY; ULCERATIVE-COLITIS; RESISTANCE GTPASES;
D O I：
10.1007/s00281-010-0224-x
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：437 / 444
页数：8
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