01497-A: Dog leukocyte antigen 88 typing in German Shepherd Dogs having pancreatic insufficiency
Grant Status: Closed
Grant Amount: $10,649
Dr. Leigh Anne Clark, PhD, Clemson University
July 1, 2010 - September 30, 2011
Sponsor(s): American German Shepherd Dog Charitable Foundation, Inc., Health & Rescue Foundation of the Petit Basset Griffon Vendeen Club of America, White Shepherd Genetics Project
Breed(s): German Shepherd Dog
Project Summary Pancreatic insufficiency in German Shepherd Dogs is caused by an autoimmune reaction that selectively destroys the pancreatic cells responsible for secreting digestive enzymes. Although once thought to be a simple recessive trait, recent work has shown that both genetic and environmental factors likely contribute to the disease. An initial whole-genome screen to identify genetic markers linked to pancreatic insufficiency yielded significant results on chromosome 12. This chromosomal region harbors the dog leukocyte antigen (DLA) system, the canine equivalent of the major histocompatibility complex (MHC), which is important in autoimmune and infectious diseases. Expression studies have shown that one MHC gene, DLA-88, is over-expressed in dogs with pancreatic insufficiency.
The objective of this work was to determine if alleles of the MHC gene, DLA-88, are genetic risk factors for exocrine pancreatic insufficiency (EPI) in the German Shepherd Dog (GSD). DLA-88 sequences were generated for 148 unrelated GSDs. Complete genotypes were determined for 132 dogs (69 cases and 63 controls). Statistical calculations were performed to assess differences in allele frequencies between cases and controls. Significant associations were found with three alleles. One allele confers an increased risk for EPI. Over 20% of EPI cases had at least one copy of this allele, whereas only one copy was observed in the control population. Two other alleles were found to confer protection against EPI. These data support a role for the immune system in the development of EPI in GDSs.