NEWS ABOUT RENAL DYSPLASIA TESING

January 2007: From Dr. Mary Whiteley, Dogenes, Inc.:

To all Lhasa Apso and Shih Tzu Breeders:

Research involving pedigree studies and analysis of the gene for JRD in three other breeds has uncovered another mutation in the same gene that was studied in the Shih Tzu and Lhasa Apso breeds. Within the other three breeds alleles A and B were present, but there were some dogs with JRD that did not have either mutation but still had JRD. This meant that there appeared to be another mutation either in the current gene, or another gene that participates in the renal dysplasia disease process.

DNA sequencing from these new breeds revealed another mutation in the same gene as the one that has alleles A & B for Shih Tzu and Lhasas. Upon further investigation, we have also located this mutation in the Shih Tzu and Lhasas. This new mutation is much stronger and has serious consequences to the gene's ability to function correctly. Because this mutation appears on the same chromosome (and the same gene) as the mutations that we have been testing for, but was not picked up earlier in the research, we are re-testing all of the dogs that were submitted in the research study and those dogs that have been tested for A & B earlier this year.

The high frequency of A and B in Shih Tzu and Lhasas appeared to be the defect we had been looking for with JRD. However, by researching the other breeds that have entered into the study that also have JRD, it was discovered that these dogs had a lower frequency of A & B and in fact only one of those breeds had mutation B.

It appears that this new mutation is inherited with the A and B alleles most of the time, and therefore the overall frequency of the disease causing mutation and the genotype (diagnosis) should not change significantly. However because of the work in all the breeds we believe that the new mutation is the actual defect.

We have developed a screening test for this mutation, and are in the process of validating this assay.

WHAT DOES THIS MEAN TO YOU:

1. All of the animals tested so far will be screened for this mutation at no cost, and the results will be reported to the owners.

2. In the future only a single genetic test will be required for the inherited defect for JRD. From this test, breeding strategies can be determined to eliminate the chromosome with the mutant allele.

3. Those people who have paid for A & B will get a credit of one test to use in the future.

Please allow us a few weeks to re-test and report results to the breeders. Those people waiting for results should get theirs within four weeks of the test being validated. We appreciate your patience and understanding. We will continue to strive to do the best research we can for the breeders.

UPDATE - June 2007: The retesting of Shih Tzu for the recently discovered defective gene associated with juvenile renal dysplasia has been completed. Of the some 100 Shih Tzu that have been retested, only five have been clear of the mutation; the others have a single copy of the mutation.* Thus far, no dogs with two copies of the mutation have been found, making it likely that two copies are lethal in utero. Dr. Mary Whiteley believes we would probably find additional clears if entire litters were tested, rather than just dogs intended for use in breeding based on other qualities. Meanwhile, because this mutation is so widespread in our breed, we need to be careful not to throw out the baby with the bath water and insist on breeding only to clear dogs, because this would involve losing other valuable qualities or introducing other diseases. Carriers bred to carriers, because they have just one copy of the mutation, can produce clears, but the elimination of this disease from our breeding programs will obviously take a long time. The credits from earlier Charitable Trust-funded A and B mutation testing will be used to test offspring of dogs already tested under the validation program, and we will provide additional information as it becomes available.

*A CLARIFICATION FOR THOSE WHO HAVE BEEN OR WILL BE TESTING THEIR DOGS: DOGENES TEST RESULTS FROM DOGS THAT HAVE JUST ONE COPY OF THE MUTATION ARE MARKED "CARRIER."

For those of you who may be confused at this point, allow me to interpret. It seems from the further research, that the initial mutations found (A & B) were not the real culprits, but another mutation is the actual mutation which causes the disease. Since the new mutated sequence is found at the same location on the same chromosome as "A" and "B" , the outcomes of the previous tests for A and B are unlikely to change. That is: animals negative for A and B are likely to be negative for the newly discovered mutation as well, and positives are likely to remain positive. Mary is going to re-test all of the previously tested samples for the newly discovered sequence. Hereafter, animals will not need to be tested for A and B, but only for the "C" gene ("c" for culprit?). Now we know what has caused the delay in getting back results. Thank you Mary, for your diligence and persistence in tracking down this killer!

Cathy Marley M.D., Editor, American Lhasa Apso Club Health Foundation Newsletter


NOTE: ASTC and ALAC funding for Mary's research ended in the spring of 2006, with the location of the A and B mutations and development of the tests for these mutations. She has continued her work with funding from other breeds affected by this disease. We thank her for sharing her latest findings with us and for opting to retest the dogs in our breed that participated in the initial research or were subsequently tested for mutations A and B at no cost. Information on the new JRD test will be posted on the Dogenes website: www.dogenes.com, and follow-up articles on the retesting program and additional research into JRD will be posted on the ASTC website as more data becomes available. Of course, the more Shih Tzu that are tested, the more we will learn. Mary would particularly like cheek-swab samples from puppies that die during their first week, to see if these puppies have two copies of this new mutation. Our thanks to those Shih Tzu owners who have participated in the research thus far, and to Mary for her ongoing efforts to enable us to eliminate this dread disease.


JoAnn Gustafson and Jo Ann White, co-chairs, ASTC Gene-Mapping Committee and Sally Vilas, Managing Director, ASTC Charitable Trust