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Genetic Testing and Research for Dogs

RENAL DYSPLASIA INFORMATION PAGE

What is RD? 
Renal dysplasia (RD) is an important category of kidney diseases in canines. Dysplasia is defined as abnormal growth or development of cells or organs. In the case of RD the kidney fails to develop properly during embryogenesis in the womb. At birth immature structures consisting of undifferentiated fetal cells or tissue types are found in the kidney, and are persistent throughout the life of the animal.

Renal dysplasia can present itself with a wide range of symptoms and pathological findings. Definitive diagnosis of RD 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 was necessary for the management and elimination of this disease.


RD- a Closer Look What you see is not always what you get. For those breeders who deny that RD is a problem in their kennel, you would see it if you had done biospies on you dogs.

Below is a summary of an article by Dr. Kenneth C. Bovee (click here for reference).

In October of 2003, Dr. Kenneth C. Bovee from the University of Pennsylvania published his findings in the Shih tzu from a 10 year study involving 143 dogs and 52 matings. His findings clearly show that the majority of breeding stock had some level of fetal glomeruli, and estimates from this study indicated that the prevalence of this defect (meaning biopsy positive fetal glomeruli) was probably about 85% in the breed, however the actual clinical cases that manifested severe renal dysfunction was low.

Other critical conclusion from this 10 year study was that animals with a low perentage of fetal glomeruli could produce those with renal disease and even the breeding of 0% fetal glomeruli (biopsy negative) adults resulted in offspring with 1-3% fetal glomeruli. The apparent low incidence of disease was a danger to the breeding population as seemingly normal adults could go undetected in the breeding population, and produce clinically affected offspring. Further, while using biopsy data to try and control this disease in the breeding population limited to some degree the production of severely affected progeny, this was not entirely successful in eliminating the transmission of biopsy positive offspring from the parents.

Further Dr. Bovee speculated, based on these findings that the mode of inheritance was not a simple recessive, and could follow a pattern of dominant with incomplete penetrance.

Thus, the development of a genetic test was imperative to control this disease in this breed as well as others.


Breeds with RD
Many breeds of dogs are afflicted with RD, and this has been documented in veterinary text books, as well as case reports and articles in the scientific literature. Of note is that RD in these breeds share a common phenotype,characterized by immature glomeruli, and/or tubules and persistent mesenchyme.

RD is largely thought of as a health problem in Lhasa apsos, and Shih Tzus.

This is not true!

How is RD inherited?
The mode of inheritance of RD has been widely debated, as this disease can present itself with a wide range of symptoms and pathological findings. Definitive diagnosis of RD 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.

The mode of inheritance of RD is dominant with incomplete penetrance.

What does Dominant with Incomplete Penetrance mean?
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.

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 mutated copy of the gene is sufficient to cause disease or recessive where two bad or mutated copies of the gene are needed to cause disease or phenotypic trait to be observed.

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 RD, 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 clinical signs of the disease. However, they can pass the disease on to their offspring. This is why a genetic test is critical to manage RD; 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 RD.

How can the RD test be used to eliminate this disorder from a breed without compromising the gene pool?
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 a mutation for renal dysplasia, do not panic. Now you have the opportunity to manage and eliminate this disease. The frequency of RD mutations 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 wild type 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.

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.