This reports describes inflammatory bowel disease 10 (IBD10), which defines a susceptibility locus for inflammatory bowel disease; the gene implicated in this disease is ATG16L1. ATG16L1 encodes a protein that plays a critical role in the process of autophagy. There is a single orthologous gene in Drosophila, Dmel\Atg16, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and loss-of-function mutations resulting from imprecise excision of TE insertions have been generated. Dmel\Atg16 is less closely related to a second ATG16 gene in human, ATG16L2.
The human ATG16L1 gene has not been introduced into flies.
Animals homozygous for an amorphic mutation of Dmel\Atg16 survive to adulthood, but exhibit abnormalities in gut morphology, an increase in markers of inflammatory response, and increased sensitivity to bacterial infection by feeding. They are also more sensitive to dextran sodium sulfate (commonly used for the induction of gut inflammation). A mutation affecting the C-terminal WD40 domain, but not one lacking N-terminal Atg5BD and CCD autophagy domains, results in similar IBD-like phenotypes. Alterations in gut flora are also detected in Atg16 mutant animals. Physical and genetic interactions have been described for Dmel\Atg16; see below and in the Atg16 gene report.
[updated Nov. 2018 by FlyBase; FBrf0222196]
Inflammatory bowel disease is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease and ulcerative colitis have a combined prevalence of 200 to 300 per 100,000 in the United States. Crohn disease may involve any part of the gastrointestinal tract, but most frequently the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. In approximately 10% of cases confined to the rectum and colon, definitive classification of Crohn disease or ulcerative colitis cannot be made and are designated 'indeterminate colitis.' Both diseases include extraintestinal inflammation of the skin, eyes, or joints. [from MIM:266600; 2018.11.09]
[INFLAMMATORY BOWEL DISEASE (CROHN DISEASE) 10; IBD10](https://omim.org/entry/611081)
[AUTOPHAGY 16-LIKE 1; ATG16L1](https://omim.org/entry/610767)
Susceptibility to Crohn disease can be conferred by variation in the ATG16L1 gene.
The protein encoded by ATG16L1 is part of a large protein complex that is necessary for autophagy, the major process by which intracellular components are targeted to lysosomes for degradation.
Many to one (2 human to 1 Drosophila); the human genes are ATG16L1 and ATG16L2.
High-scoring ortholog of human ATG16L1; moderate-scoring ortholog of ATG16L2 (1 Drosophila to 2 human). Dmel\Atg16 shares 38% identity and 60% similarity with ATG16L1; it shares 30% identity and 47% similarity with ATG16L2.
