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Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs

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Abstract

Exocrine pancreatic insufficiency (EPI) is a disease wherein pancreatic acinar cells fail to synthesize and secrete sufficient amounts of digestive enzymes for normal digestion of food. EPI affects many dog breeds, with a dramatically higher prevalence in the German shepherd dog (GSD) population. In this breed and perhaps others, EPI most often results from degeneration of the acinar cells of the pancreas, a hereditary disorder termed pancreatic acinar atrophy (PAA). Evidence of lymphocytic infiltration indicates that PAA is an autoimmune disease, but the genetic etiology remains unclear. Data from global gene expression and single nucleotide polymorphism profiles in the GSD suggest the involvement of the major histocompatibility complex [MHC; dog leukocyte antigen (DLA)]. To determine if alleles of the MHC influence development of EPI, genotyping of polymorphic class I (DLA-88) and II loci (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was carried out for 70 affected and 63 control GSDs, and four-locus haplotypes were determined. One haplotype containing a novel allele of DLA-88 is very highly associated with EPI (OR > 17; P = 0.000125), while two haplotypes were found to confer protection from EPI (P = 0.00087 and 0.0115). Described herein is the genotyping of MHC class I and II loci in a GSD cohort, establishment of four-locus haplotypes, and association of alleles/haplotypes with EPI.

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Acknowledgments

This work was funded by grants from the Canine Health Foundation (#1497-A and 934). Parts of the work were also supported by the National Science Foundation-Research Experiences for Undergraduates program (0453360) and a Pepsi Refresh Project award (Health Category, 2010). The authors wish to thank EPI4dogs and the many owners and veterinarians who contributed to this project.

Conflicts of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Genetics and Biochemistry, College of Agriculture, Forestry and Life Sciences, Clemson University, 154 Poole Agricultural Center, 130 McGinty Ct, Clemson, SC, 29634, USA

    Kate L. Tsai, Alison N. Starr-Moss, Christopher Robinson & Leigh Anne Clark

  2. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Gopalakrishnan M. Venkataraman

  3. Centre for Integrated Genomic Medical Research, School of Medicine, University of Manchester, Manchester, UK

    Lorna J. Kennedy

  4. Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA

    Jörg M. Steiner

Authors
  1. Kate L. Tsai
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  2. Alison N. Starr-Moss
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  3. Gopalakrishnan M. Venkataraman
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  4. Christopher Robinson
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  5. Lorna J. Kennedy
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  6. Jörg M. Steiner
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  7. Leigh Anne Clark
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Corresponding author

Correspondence to Leigh Anne Clark.

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Tsai, K.L., Starr-Moss, A.N., Venkataraman, G.M. et al. Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs. Immunogenetics 65, 501–509 (2013). https://doi.org/10.1007/s00251-013-0704-y

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  • DOI: https://doi.org/10.1007/s00251-013-0704-y

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