Richard E. Goldstein, DVM

Q & A about the PHPT Genetic Test in Keeshonden
Laboratory of Richard E. Goldstein, DVM

1. What does the PHPT genetic test do?
The test evaluates a gene associated with primary hyperparathyroidism (PHPT) in the Keeshond.
2. What kind of genetic test is it?
It is a linkage test with 100% association to the disease PHPT. This means that the test is for a site in the DNA either within the gene itself or very, very close to the gene, so it is linked to the disease.
3. What mode of inheritance does PHPT follow?
PHPT is transmitted/inherited by an autosomal dominant gene. This means that an abnormal gene from one parent is all that is necessary to pass on PHPT to the offspring, regardless of whether or not the other parent also has the affected gene. Either a Keeshond has the affected gene, or it does not. There are not designations such as carrier, clear or affected, as identified when a gene is recessive.
4. What are the possible test results and what do they mean?
The report will show either a NEGATIVE or a POSITIVE result. A NEGATIVE result indicates that the affected form of the gene is not present and the dog is very unlikely to develop the disease. A POSITIVE result indicates that the affected form of the gene is present in the tested dog. Dogs that possess this form of the gene are very likely to develop primary hyperparathyroidism as they become older, even if they are healthy at the time the test was performed.
5. If I receive a positive test result but my Keeshond is only 2 years old, what steps should I take?
This gives you an unprecedented opportunity to use this knowledge to give your Keeshond the best care possible. Begin to monitor the calcium level on a regular schedule, preferably once a year starting around the age of four, so that you may catch the disease in its earliest stages, before potential complications occur. Talk with your vet about specialists in the area that treat the disease. You have time to plan ahead and seek out qualified, skilled care in advance.
6. If a Keeshond receives a POSTITIVE result for the PHPT genetic test, how would that affect a planned breeding using the dog or bitch?
If a Keeshond that has tested POSITIVE is used for breeding, 50% of the offspring will have one copy of the defective gene and 50% will not. If a Keeshond with the defective gene is bred to another Keeshond who also has the defective gene, 50% of the offspring will have one copy of the defective gene, 25% will have two copies of the normal gene and 25% will have two copies of the defective PHPT gene. Based on our research, it appears that embryos in this last group with two copies of the defective gene may actually not survive in utero, resulting in smaller litter sizes for this type of breeding. Remember, it only takes one copy of the defective gene to pass the disease on to the offspring.
7. What is "age dependent penetrance?"
PHPT affects older Keeshonden with what is known as "age dependent penetrance." This means that the test does not identify clinical disease at the time of testing; it indicates the presence of the defective gene, or the genetic potential to develop the disease later in life. The vast majority of Keeshonden with the defective gene will develop PHPT if they live long enough.
8. How much does the test cost?
The test is $99.00 per sample. Two or more littermates, age 12 weeks or younger, submitted together, are $89.00 per sample. A show discount of $89.00 per sample is available for a group of 10 or more samples (owners may be different) submitted together, with results reported to the same veterinarian. Effective January 2, 2008, payment must be included with the sample(s) submitted for testing. For more information, please contact Dr. Belinda Thompson at bt42@cornell.edu or 607-253-3908.
9. PHPT is also a problem in other countries. How does someone submit a sample if they live outside the U.S.?
Samples will be tested from other countries but must follow the guidelines revised on July 6, 2006 by the USDA. The veterinarian needs to include a declaration statement to allow passage of the sample without a permit. For more information and guidelines, see the website at: http://www.aphis.usda.gov/vs/ncie/icatdog.html
10. How long will it be before my vet receives the test results?
Your vet should have the results within 14 business days. Your vet will receive a fax from the AHDC and within 2 weeks of reporting, should also receive a certificate from the Goldstein Molecular and Genetics Laboratory.
11. Why do I have to fill out two different submission forms to submit with the sample?
There are two forms, one for the Cornell Animal Health Diagnostic Center and one for the Goldstein Molecular and Genetics Laboratory. The sample is sent to the AHDC, who initially processes the paperwork and then transfers the sample to the Goldstein Laboratory for testing and genetic analysis.
12. How do I submit a sample for testing?
Your vet will draw blood from your Keeshond for the test and send 1-2 mls of whole blood in an EDTA (purple top) tube. The tube should NOT be spun and should be stored in the refrigerator until it is to be shipped.
13. How should the sample be shipped?
It should be shipped with frozen freezer packs in an insulated Styrofoam container or Styrofoam tube mailer (tube mailer available from the AHDC for a small fee, if needed). It should be shipped by overnight courier or by U.S. Priority Mail. Samples should be scheduled to arrive Monday through Friday. The AHDC offers special pricing for courier services, further information is available at: http://www.diaglab.vet.cornell.edu/test/feeman/CourierInfo.pdf If you have any questions about sample collection, submission requirements or shipping, please contact the Animal Health Diagnostic Center at (607) 253-3333 or refer to the AHDC website at http://www.diaglab.vet.cornell.edu
14. Where does the veterinarian send the sample?
Use the address listed on the Animal Health Diagnostic Center submission form.
By U.S. mail: P.O. Box 5786, Ithaca NY 14852-5786
By courier service: Upper Tower Road, Ithaca NY 14853
15. Who do I contact if I have any questions about PHPT or the PHPT genetic test?
Contact Dr. Goldstein by email at phpt@cornell.edu or by phone at 607-253-4480. Please leave a message and your call will be returned.