Host Genetics in Granulomatous Colitis
27th ECVIM-CA Congress, 2017
Kenneth W. Simpson
College of Veterinary Medicine, Cornell University, Ithaca, NY, USA

Keynote Message

Granulomatous colitis (GC) is a severe inflammatory bowel disease (IBD), typically diagnosed in boxer dogs and French bulldogs, but also other mastiff breeds, younger than four years of age. Affected dogs have diarrhea that leads to chronic weight loss, anemia, and debilitation. Previous studies have identified invasive bacteria within immune system cells, macrophages, in the colons of diseased dogs. Antibiotic treatments usually yield clinical improvement; however, antibiotic-resistant bacteria are present in some cases and persistently affected dogs suffer greatly. Elimination of this disease would be greatly facilitated by a genetic screening test to identify carriers. Identifying the genetic basis of GC could also provide comparative insights to inform the diagnosis and treatment of people with CD/IBD. Using a GWAS approach we have identified a region of DNA on chromosome 38 that is strongly associated with GC. It contains multiple genes that are known to impact the killing of E.coli bacteria and inflammatory responses. To identify the specific gene or genes that are affected, we are analyzing DNA sequences and expression patterns of these genes in dogs with GC and controls.

Key References

1.  Simpson KW, Dogan B, Rishniw M, Goldstein RE, Klaessig S, McDonough PL, German AJ, Yates RM, Russell DG, Johnson SE, Berg DE, Harel J, Bruant G, McDonough SP, Schukken YH. Adherent and invasive Escherichia coli is associated with granulomatous colitis in boxer dogs. Infect Immun. 2006;74(8):4778–92.PMID:16861666.

2.  Manchester AC, Hill S, Sabatino B, Armentano R, Carroll M, Kessler B, Miller M, Dogan B, McDonough SP, Simpson KW. Association between granulomatous colitis in French bulldogs and invasive Escherichia coli and response to fluoroquinolone antimicrobials. J Vet Intern Med. 2013;27(1):56–61. doi: 10.1111/jvim.12020. Epub 2012 Dec 3.PMID:23206120.

3.  Hayward JJ, Castelhano MG, Oliveira KC, Corey E, Balkman C, Baxter TL, Casal ML, Center SA, Fang M, Garrison SJ, Kalla SE, Korniliev P, Kotlikoff MI, Moise NS, Shannon LM, Simpson KW, Sutter NB, Todhunter RJ, Boyko AR. Complex disease and phenotype mapping in the domestic dog. Nat Commun. 2016;7:10460. doi: 10.1038/ncomms10460.PMID:26795439.

4.  Berger SB, Romero X, Ma C, Wang G, Faubion WA, Liao G, Compeer E, Keszei M, Rameh L, Wang N, Boes M, Regueiro JR, Reinecker HC, Terhorst C. SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages. Nat Immunol. 2010;11(10):920–7. doi: 10.1038/ni.1931. Epub 2010 Sep 5.PMID:20818396.

5.  Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119–24. doi: 10.1038/nature11582.20818396.

  

Speaker Information
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Kenneth W. Simpson
College of Veterinary Medicine
Cornell University
Ithaca, NY, USA


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