AN UPDATE ON RENAL DYSPLASIA/DNA

*Update* The RD test is now available see www.dogenes.com for details.

Feb. 2006 Renal Dysplasia Update- One gene two mutations

It is apparent that understanding renal dysplasia in dogs has been difficult. Sometimes animals have displastic kidneys with no apparent clinical manifestations. In extreme cases entire litters are wiped out as a result of RD. Because of these differences, we DNA sequenced our candidate gene from two unrelated puppies that were diagnosed at a very early age with RD, and most of their siblings were also affected with RD. The results of these experiments revealed that there is a second mutation in our candidate gene, and that these puppies had both the first mutation discovered as well as the second mutation. This was in the Shih Tzu breed. We have yet to get samples that fit this description from Lhasa Apso breeders, although we have been contacted about this problem.

This is an extremely important discovery in that it could explain why some litters have devastating cases of RD if these mutations are determined to be the cause of RD.

A screening test has been developed for both mutations, and we are currently looking at these mutations in the dogs that have been submitted for our pedigree study. There is still a need for samples for this study, so we are encouraging breeders with this problem to contact Dogenes.
Mary Whiteley http://www.dogenes.com

Renal Dysplasia Breakthrough!

A mutation has been identified in one of the candidate genes for renal dysplasia. This discovery looks very promising as this mutation is found in all seven RD dogs (both Lhasa Apsos and Shih Tzus) examined to date. Additionally, this mutation is absent in two dogs that are RD negative by biopsy and two control breeds not known to have RD.

If this mutation is found to be the cause of renal dysplasia, it is highly likely that this mutation is present in other breeds with renal dysplasia that share similar clinical and pathological findings to those found in Lhasa Apsos and Shih Tzus.

Currently, a screening test is being developed so that a pedigree study can be conducted in these breeds to determine if there is a correlation between the presence of this mutation and the disease. Also these studies should help to unravel the mode is inheritance of this disease which has been poorly understood to date.

If the research validates this mutation as the cause of renal dysplasia, then the development of a screening test will also be an invaluable tool to manage and eliminate this disease in many breeds.
see www.dogenes.com

AN UPDATE ON RENAL DYSPLASIA/DNA RESEARCH AND FUNDRAISING
Through the miracle of modern science, research is being done to identify the gene mutation responsible for causing Renal Dysplasia and to develop a noninvasive cheek swab test to identify dogs likely to produce the disease so they can be appropriately used in our breeding programs. Dr. Mary Whiteley of GeneSearch is currently sequencing her suspect gene. Dr. Whiteley hypothesizes the disease is caused by a dominant gene with incomplete penetrance. The potential test would identify genotypically affected animals.
The Lhasa Apso Club of Central Colorado has supported this research project donating money for reagents needed during the research project.
Caring about the welfare of the breed involves much more than showing dogs and breeding puppies. We are hopefully close to finding a way to eliminate this terrible disease. Please, won't you help us do so!
Lhasa Apso Club of Central Colorado Research Fund
8391 London Lane
Conifer, CO 80433

WHAT IS RENAL DYSPLASIA?

Renal Dysplasia is a defect of the kidneys. It is found most commonly in Shih Tzu, Soft Coated Wheaten Terriers and Lhasa Apsos.

The dog is born with relatively immature kidneys. This changes rapidly in the first six weeks of life. In many animals, immature nephrons (urine-forming units) exist until 6-10 weeks of age. But in this disease, these immature nephrons persist throughout life. Also, some nephron units do not develop and are replaced with fibrous tissue. Sometimes this fibrous tissue represents 20-50% of the kidney, and the kidneys are noticably small and irregular.

Other evidence of RD includes diffuse interstitial fibrosis in the cortex and medula (which seems quite peculiar to this disease), reduced numbers of glomeruli (the filtering structure of the kidney where toxins, fluid and electrolytes are removed from the blood), dilated and hypoplastic tubules (through which the fluid or filtrate passes while being transformed into final urine), and a variety of sizes of glomeruli. Some glomeruli are 20-30% smaller than normal, some are normal size, and some are embryonic. While mineralization of tubules can be seen in any chronic renal disease, this mineralization is seen with JRD even in young animals that have only moderate uremia. Researchers believe that this mineralization is somehow an early component of this disease and is related to the abnormal development of the nephrons. Dogs with RD have had an embryonic arrest some time around birth. Hypertension does not seem to be part of this disease.

Affected dogs are characterized by the percentage of hypoplastic glomeruli:
Dogs with 1-2% hypoplastic glomeruli are borderline.
Dogs with 2-15% are mild.
Dogs with 15-25% are moderate.
Dogs with 25-35% are moderately severe.
Dogs with over 35% hypoplastic glomeruli are severe.

RD is poorly recognized because many animals are only slightly affected. They show no clinical signs, and the presence of the disease may fail to be detected by routine laboratory tests, including urinalysis, serum creatinine, BUN, radiographs of renal size, and ultrasound. Many moderately and slightly affected dogs will live normal life spans with apparently normal renal function and can pass on the disease to their offspring. Due to the nature of this disease it can go undetected for many generations or be ignored by knowledgeable breeders because only a small percentage of animals will die of renal failure. Without the development of more effective tests than those presently available, the disease is going to be with us for a long time because it is transmitted in a very silent fashion by many animals that appear clinically normal.

Basic Genetic Concepts

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