Hunting for Hereditary Diseases in the German Shepherd

German Shepherd Dogs (GSDs) are one of the most popular dog breeds in the U.S. – in 2010 they had the second highest number of registrations in the American Kennel Club. Unlike many dog breeds, these strong, intelligent dogs have been bred less for a specific appearance and more for aptitude and temperament. That’s one of the reasons that shepherds are not just beloved as companion dogs but also used as working dogs by police departments, militaries, and other organizations around the world.

Unfortunately, even though the GSD population is quite large, and relatively physically diverse, more than 50 hereditary diseases have been identified in the breed. If scientists could identify the genes responsible, and develop tests to locate affected dogs, the frequency of these diseases could be reduced, and more shepherds could live full and healthy lives. That is the task that Dr. Leigh Anne Clark and colleagues took upon themselves with the help of the AKC Canine Health Foundation – testing whether a simple and efficient technique could be used to identify the causes of a variety of hereditary genetic diseases in German Shepherd dogs.

The scientists were researching whether genome-wide association studies using single nucleotide polymorphisms (SNPs) could be used to identify the chromosomal regions associated with four common diseases seen in GSDs - pituitary dwarfism, degenerative myelopathy, congenital megaesophagus, and pancreatic acinar atrophy. Using samples from 197 shepherds, they first tested the technique on a harmless genetic variation with a known cause – a white coat. Once they found that it correctly mapped to the expected location on chromosome 5, they expanded their investigation to the unknown causes of the four inherited diseases.

The genetic analysis found clear chromosomal association for three of the diseases. Pituitary dwarfism was found to be strongly associated with a region of chromosome 9 that contains a plausible candidate gene – LHX3. Degenerative myelopathy was strongly associated with two regions on chromosome 31, near a previously identified point mutation, and also potentially with a region on chromosome 10. Finally, congenital megaesophagus was associated with a whole block of mutations on chromosome 12. Only pancreatic acinar atrophy was not clearly associated with a single, or small group of genes – and this was not wholly surprising. Researchers had previously suggested that this autoimmune condition, which is the most common cause of exocrine pancreatic insufficiency, might either be caused by multiple genes with small effects or actually be a constellation of similar diseases caused by different genes in different dogs.

This type of SNP association study is a great first step for mapping the chromosomal location of hereditary diseases in dogs. Hopefully, additional studies will provide even more information about the causes of these diseases and eventually lead to reliable tests and treatments that can improve the health of our beloved German Shepherd dogs.

This work was funded by AKC Canine Health Foundation Grant 934.

Scientific Publication:

Tsai, K.; Noorai, R.; Starr-Moss, A.; Quignon, P.; Rinz, C.; Ostrander, E.; Steiner, J.; Murphy, K. & Clark, L. Genome-wide association studies for multiple diseases of the German Shepherd Dog Mammalian Genome, Springer New York, 1-9