THE RESULTS FROM THE PEDIGREE STUDY ARE IN.
WE HAVE THE GENE AND THE MUTATION(S)!
Our pedigree study is complete. We have examined the two mutations discovered in our candidate gene in Shih Tzus, and one mutation in common with both Shih Tzus and Lhasa apsos. In 100% of the cases of clinical samples (either biopsied, or by abnormal results on blood and urine tests of kidney function) the individual had either one or the other mutations. In four Shih Tzu litters that were severely affected, the puppies had both mutations. In some cases where the dogs appeared to be normal they also had the mutation(s). The only clear dogs in this study were clear by biopsy. 13 non RD breed dogs were also examined, they they did not have either of the mutations. All of this data taken together indicates a mode of inheritance that is dominant with incomplete penetrance. We are denoting the first mutation as A and the second as B, and are continuing to investigate if mutation B is also in Lhasa apsos, or other breeds.
We have found the mutation A in two Miniature schnauzers , and a Poodle with JRD.
These results are in absolute agreement of a 10 year study conducted at University of Pennsylvania by Dr. Kenneth Bovee. His findings also showed a mode of inheritance that is consistent with dominant with incomplete penetrance. The results are likewise consistent with the wide range of clinical manifestations and the sudden appearance of the disease from apparently normal parents.
DEFINITION: DOMINANT WITH INCOMPLETE PENETRANCE:
Mutations that do not fit a simple pattern of Medelian inheritance, and show variable degrees of clinical symptoms (variable expressively of the gene) are said to be inherited with incomplete penetrance. Simply put, this means that individuals with one or two copies (in the case of dominant mutations) can appear to be normal, but can pass on a trait with varying degrees of clinical manifestations to their offspring. In the case of JRD this can be from normal to having a positive biopsy with no clinical signs of kidney disfunction to severely affected. This is also consistent with the wide range of biopsy findings (% of fetal glomeruli) and individuals with a relatively high percentage of fetal glomeruli, that are still able to concentrate urine.
A genetic test is the only way to identify and manage this disorder, and eliminate this from the breeds.
Members of the American Shih Tzu Club can now order tests.
Note: We are currently looking for samples from clinically affected dogs with juvenile renal dysplasia from all breeds known to have this disease. Any owners or breeders that have samples should contact Dogenes at .
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To: All Lhasa Apso Breeders
At the end of 2005, the Renal Dysplasia Researcher, Mary Whiteley, PhD University of Ottawa, decided to move back to her native Canada to be closer to her family. She has reconstituted her company in Canada with a new name, Dogenes. The website with RD research information is at: http://www.dogenes.com
The American Shih Tzu Club is also supporting her research and she is applying for an "acorn grant" from the AKC Canine Health Foundation.
In Mary's last progress report to me, she said she had completed the sequencing of three genes without finding a mutation associated with renal dysplasia. These three genes have been put into the public domain; she is not patenting them. Mary is now working on a fourth gene that is involved with the development of the fetal glomeruli. Mary is 100% determined to find the right gene and develop a real test for us.
On Mary's new website, you will see a database for Lhasa Apsos. Mary is offering this free to ALAC members and non-members who donate towards the research. The database will provide owners with a place to publish the results of their dogs' RD tests IF they wish to do so.
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From: DNA Solutions LLC,
11014 Schuylkill Rd.,
Rockville, MD, 20852
301-881-2235
We wish to thank you for your support in our efforts to uncover a mutation responsible for renal dysplasia in your breed. This includes the parent club, the American Lhasa Apso Club, as well as the Lhasa Apso Club of Central Colorado.
We are pleased to announce that we have discovered a mutation in our candidate gene that could account for this disease. To this end, we are persuing a
screening test and pedigree study to confirm our findings. In principal, the identified mutation should affect the biological function of the gene in question. We still have a lot of work to do to confirm that this mutation is the cause of renal dyplasia in your breed. We have DNA sequenced the entire gene from an affected Lhasa, as well as another breed not known to have RD.
All interested participants, and other breeds afflicted with juvenile RD should contact us at www.dogenes.com or 301-881-2235 or 301-770-3586.
Again, this is a very exciting first step in solving this problem in Lhasa's and other breeds.
Thank you so much,
Mary H. Whiteley, Ph.D.,
President, DNASolutions LLC
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