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Associations between gastric dilatation-volvulus in Great Danes and specific alleles of the canine immune-system genes DLA88, DRB1, and TLR5

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  • 1 Department of Transplantation Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 2 Department of Transplantation Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 3 Department of Transplantation Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 4 Department of Clinical Biostatistics, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 5 Department of Clinical Research Division, and the Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.
  • | 6 Department of Transplantation Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109.

Abstract

OBJECTIVE To determine whether specific alleles of candidate genes of the major histocompatibility complex (MHC) and innate immune system were associated with gastric dilatation-volvulus (GDV) in Great Danes.

ANIMALS 42 healthy Great Danes (control group) and 39 Great Danes with ≥ 1 GDV episode.

PROCEDURES Variable regions of the 2 most polymorphic MHC genes (DLA88 and DRB1) were amplified and sequenced from the dogs in each group. Similarly, regions of 3 genes associated with the innate immune system (TLR5, NOD2, and ATG16L1), which have been linked to inflammatory bowel disease, were amplified and sequenced. Alleles were evaluated for associations with GDV, controlling for age and dog family.

RESULTS Specific alleles of genes DLA88, DRB1, and TLR5 were significantly associated with GDV. One allele of each gene had an OR > 2 in the unadjusted univariate analyses and retained a hazard ratio > 2 after controlling for temperament, age, and familial association in the multivariate analysis.

CONCLUSIONS AND CLINICAL RELEVANCE The 3 GDV-associated alleles identified in this study may serve as diagnostic markers for identification of Great Danes at risk for GDV. Additional research is needed to determine whether other dog breeds have the same genetic associations. These findings also provided a new target for research into the etiology of, and potential treatments for, GDV in dogs.

Abstract

OBJECTIVE To determine whether specific alleles of candidate genes of the major histocompatibility complex (MHC) and innate immune system were associated with gastric dilatation-volvulus (GDV) in Great Danes.

ANIMALS 42 healthy Great Danes (control group) and 39 Great Danes with ≥ 1 GDV episode.

PROCEDURES Variable regions of the 2 most polymorphic MHC genes (DLA88 and DRB1) were amplified and sequenced from the dogs in each group. Similarly, regions of 3 genes associated with the innate immune system (TLR5, NOD2, and ATG16L1), which have been linked to inflammatory bowel disease, were amplified and sequenced. Alleles were evaluated for associations with GDV, controlling for age and dog family.

RESULTS Specific alleles of genes DLA88, DRB1, and TLR5 were significantly associated with GDV. One allele of each gene had an OR > 2 in the unadjusted univariate analyses and retained a hazard ratio > 2 after controlling for temperament, age, and familial association in the multivariate analysis.

CONCLUSIONS AND CLINICAL RELEVANCE The 3 GDV-associated alleles identified in this study may serve as diagnostic markers for identification of Great Danes at risk for GDV. Additional research is needed to determine whether other dog breeds have the same genetic associations. These findings also provided a new target for research into the etiology of, and potential treatments for, GDV in dogs.

Supplementary Materials

    • Supplementary Figure 1 (PDF 39 kb)
    • Supplementary Figure 2 (PDF 40 kb)
    • Supplementary Figure 3 (PDF 17 kb)
    • Supplementary Figure 4 (PDF 19 kb)
    • Supplementary Table 5 (PDF 125 kb)

Contributor Notes

Address correspondence to Dr. Harkey (mharkey@fredhutch.org).

Ms. Villagran's present address is Department of Psychology, College of Arts and Sciences, Baylor University, Waco, TX 76798.

Dr. Harkey and Ms. Villagran contributed equally to this work. Drs. Venkataraman, Leisenring, Hullar, and Torok-Storb also contributed equally to this work.