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PHPT genetic marke ID'd

January 1, 2007
Krista Schultz

New York - Grant-funded research yielded the discovery of a genetic marker linked to primary hyperparathyroidism (PHPT) prevalent in Keeshonden.

NEW YORK — Grant-funded research yielded the discovery of a genetic marker linked to primary hyperparathyroidism (PHPT) prevalent in Keeshonden.

Dr. Richard Goldstein, associate professor of small animal medicine at Cornell University's College of Veterinary Medicine and diplomate of the American College of Veterinary Internal Medicine, used an American Kennel Club (AKC) Canine Health Foundation grant to determine that dogs that test positive for the marker associated with PHPT are more likely to develop the disease as they get older, even if unaffected at the time of testing.

"We are able to develop the test and offer the test, which is very important from the breed perspective," Goldstein says. "There is still a lot to learn about the disease itself and the genetics of the disease. We can now at least give the dog owners and breeders more information about their dogs."

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PHPT is an inherited, late-onset disease that typically causes tumors to grow in the parathyroid, hindering its ability to regulate the dog's blood calcium level. Without treatment, an affected dog may eventually die of PHPT complications, most often kidney failure.

"PHPT is something that they have been dealing with for a long time," says Erika Werne, director of Canine Research and Education for AKC, of the Keeshond breed. "It is something that is late onset, so an animal in a breeding program can already be bred several times before it shows symptoms of the disease, and this perpetuates the problem."

With the AKC grant and sponsorship by the Keeshond Club of America, Goldstein says he was fortunate to have good timing, including the publication of the canine genome and the availability of new technology from the Broad Institute at MIT. Goldstein originally obtained a grant from the Cornell Center for Genomics to establish a 200-sample DNA bank of both affected and non-affected research candidate genes, and then used the AKC's funds to perform the genetic research.

"It's been real exciting the last nine to 10 months to see people using the information from the canine genome sequence," Werne says.

The research efforts to confirm the location of the specific mutation causing the disease will continue, and Goldstein says he hopes to soon identify the gene that causes PHPT with certainty. The availability of the current test for PHPT should allow its eventual removal from the Keeshond breed, which is 50 times more likely to the have the disease than other breeds.

"We are not 100 percent certain that we have actually found the gene, but if we haven't, we are very, very close," Goldstein says. "I'm pleased. But, as with all research, I try not to get too excited with successes or too upset with failures."

During his residency in the mid-90s at the University of California-Davis School of Veterinary Medicine, Goldstein developed a novel therapy for PHPT working with many afflicted dogs, especially Keeshonden. He remained interested in the disease and said he now hopes to identify the gene with certainty.

"The grant is to find the specific genetic cause. He's found the genetic marker, so the rest of the grant will be to refine that to prove that it is a particular protein. We're really excited," Werne says.

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