There is two situations for your dog. 1) if it is a carrier 2) if it has the disease. After doing a little research and reading this thread. "If" the DNA test does work, it will only tell you if the dog is a carrier of JRD but it will not tell you if it has JRD. "Definitive diagnosis of JRD is done by a wedge biopsy which reveals dysplastic lesions, including abnormal ducts, and glomeruli. Individuals with an abnormal biopsy can be asymptomatic, showing no signs of the disease..." (see below) Please correct me if I am wrong here.
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http://www.dogenes.com/
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How is JRD inherited? More...
The mode of inheritance of JRD has been widely debated, as this disease can
present itself with a wide range of symptoms and pathological findings.
Definitive diagnosis of JRD is done by a wedge biopsy which reveals dysplastic
lesions, including abnormal ducts, and glomeruli. Individuals with an abnormal
biopsy can be asymptomatic, showing no signs of the disease, On the other
hand, they may present with classic signs of chronic end stage renal failure, or
somewhere between these two extremes. Given this broad spectrum of
symptoms affected individuals often go unnoticed, and remain in the breeding
population. This is why development of a genetic test is critical to the
management and elimination of this disease. Further a genetic test can be used
to show the mode of inheritance .
Through pedigree studies, the mode of inheritance was finally revealed as
Dominant with Incomplete Penetrance.
What does Dominant with Incomplete Penetrance mean? More...
Dominant with incomplete penetrance refers to a situation where an inherited mutation may or may not be expressed in an individual.
The traits that we see in an individual are collectively known as the "phenotype", while the "genotype" refers to genetic constitution or makeup of
an individual.
Penetrance refers to the frequency that the phenotype (or some characteristics of the disease) is observed. If, for example, the penetrance. is 75%, then the chances of offspring to develop a disease are 3 out of 4. In the case of JRD, the penetrance is low with a penetrance. estimated to be about 2-5%. Therefore only a small number of individuals with the mutation will show signs of the disease. However, they can pass the disease on to their offspring. This is why a genetic test is critical to manage JRD; this is the only way to
eliminate this disorder. There may be risk factors or triggers that are yet undiscovered that may increase the chances of an individual to develop JRD.
A mutation is a permanent change in the DNA sequence of a gene, whether itis good, bad or neutral. Mutations that cause a genetic disease can be inherited as dominant where one bad copy of the gene is sufficient to cause disease or a phenotypic trait to be observed, or recessive where two bad or mutated copies of the gene are needed to cause disease or phenotypic trait to be observed.
All chromosomes exist in pairs in the nucleus of cells. Each pair is comprised of one chromosome from the sire and one from the dam. Therefore, every animal has two copies of every gene. In dogs there are 78 chromosomes, or 39 pairs.
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Development of a Genetic test at DOGenes More...
During the development of the fetus, certain genes act in a pathway or cascade to direct the development of the various organs and structures that make up the body (think of it as dominos: if one domino is missing the other ones wont perform their task in the array). Since every cell contains two copies of every gene, one non-mutated copy may be sufficient to complete to cascade (recessive inheritance). The human genome contains about 20,000 to 25,000 genes, and the canine genome is likely to contain about the same
number. Of these several hundred or More... may be dedicated to the maturation of specific organs. Not all of these Òtissue specificÓ genes are absolutely essential to the development of specific cell types, as has been shown in Òknockout miceÓ, where genes have been completely eliminated with no observable effect on the animal. In the case of renal dysplasia in model organisms such as the mouse, mutated transcription factors (genes that code for proteins that turn on other genes) or growth factors (genes that code for
proteins that promote the growth of cells), have been implicated in causing the disease.
One approach to discover genes that are cause genetic diseases is to use candidate genes known to cause specific diseases in model organisms, like the mouse, rats, zebra fish or even the lowly fruit fly.
This was the approach used in the quest to find the mutation for JRD in dogs. After DNA sequencing six candidate genes, the causative mutation was finally uncovered in a gene in Lhasa apsos, and Shih Tzus. This mutation was then discovered in other breeds with JRD, and a direct genetic test is now available for many breeds afflicted with this disorder.
Through pedigree studies, the mode of inheritance was finally revealed as Dominant with Incomplete Penetrance.
How can the new test be used to eliminate this disorder from a breed
without compromising the gene pool? More...
Genetic tests are designed to manage and eventually eliminate disorders without compromising the diversity in a gene pool. If you have just found out that your dog carries the mutation for juvenile renal dysplasia, do not panic. Now you have the opportunity to manage and eliminate this disease. The frequency of this mutation is extremely high in many breeds. This mutation has been elusive and impossible to eliminate prior to the development of a genetic test, as the disease appears sporadically because it is inherited with incomplete penetrance, meaning that an animal that carries this mutation may or may not show clinical signs of the disease, but can still pass it on to the next generation.
As in any breeding you must consider the positive and negative traits of each partner, and how the parents traits can best balance and compliment each
other.
All dogs (and living organisms) are carriers of multiple mutations.
If a genetic disease is produced in an animal, it is not necessarily the result of poor breeding practices, but is the nature of inheritance as a random event. Although the exact mutation rate for canines is difficult to determine, by extrapolation from other species, there is a good chance that every individual produced has a new mutation in some gene. Therefore, with every generation of breeding, new mutations arise, but since they are present at a low frequency, they are generally lost in subsequent breeding. There is no such
thing as a perfect animal!
Chromosomes exist in cells in pairs, one from the sire and one from the dam. Dogs have 39 sets of chromosomes. Each set or pair is composed of two chromosomes, one from the sire, and one from the dam. In the case of a simple recessive mutation, one of the chromosomes, either from the sire or the dam, makes enough protein from for the animal to survive. Therefore, the Òwild typeÓ chromosome of the pair provides enough protein (gene product) to compensate for the chromosome that carries a mutation. In the case of a
dominant mutation, only one copy of the chromosome carrying the mutation is necessary to produce disease.
With the identification of one of the many mutations that your animal carries, you can now proceed to at least eliminate this identified mutation, and not inadvertently select for another deleterious mutation that your animal carries. Wholesale elimination of carriers is the worst decision that you can make as this would deplete the gene pool.
As in any breeding you must consider the positive and negative traits of each partner, and how the parents traits can best balance and complement each other.
What information does this DNA test actually tell the breeder? More...
The DNA test results are reported as follows:
a) Carrier - (one copy of the JRD mutation)
b) Homozygous mutant allele = Homozygote (two copies of the JRD mutation)
c) Clear - No copies o f the JRD mutation are present.
With a & b results above Ñ the animal is potentially affected by JRD or
could pass it on to its progeny.