Basic facts:   Renal Dysplasia is the failure of normal development of the kidney. Gradually increasing symptoms include excessive thirst and volume of urine, weight loss, lack of vigor, intermittent loss of appetite and eventual kidney failure often beginning at less than one year of age. The veterinary literature shows that the hereditary disease occurs in thirty-one breeds. VetGen has discovered a linked DNA marker to a required genetic determinant of juvenile renal dysplasia (JRD) in the above three breeds. There is strong linkage between this marker and the defective gene such that about 95% of the definitely affected dogs in these breeds have one or two copies of an allele we have called M (standing for marker). At this marker locus, there is only one other allele called N (for normal). The population frequency of the M allele in the three breeds is about 30%.

Usefulness of Test:   There is a high level of association of the M marker with a JRD determining gene. Depending on whether our marker is associated with a dominant-determinant or a recessive-determinant gene of JRD, the degree of predictability of the M marker for JRD susceptibility will vary a little. We have selected 80% as a conservative estimate of the predictability.

The simplest way to understand the value of this test is to consider the following. If you breed such that you produce an N/N puppy, you will have an 80% probability that you have produced a genotype that can’t get JRD. Restated, you have decreased the risk of your puppy getting JRD by 80%.

Perhaps we can use an example that is more intuitively obvious. Let’s say that in a given breed, 70% of the dogs are green, and 30% pink. But the risk of producing JRD is four times higher when a pink puppy is born than if a green puppy is born. Assuming there is no particular advantage to having a pink coat, breeders interested in reducing JRD in their lines and their dogs should greatly reduce breedings that would produce pink-coated puppies. In this example, the pink coat color is a marker the breeder can see. In the actual situation, the M marker is a marker VetGen can help you see. In the very simplest of terms, breeding away from the M marker significantly reduces the risk of JRD in puppies you produce.

Frequently Asked Questions.

Question:   What about the genetics of JRD? Shouldn’t the actual underlying genetic situation be known before breeders act?

Answer:   The underlying genetics of JRD is not known at present, and may not be known for some time. Theories include:
1) That abnormalities in two genes, one dominant and one recessive, must simultaneously be present.
2) That a common dominant gene with incomplete penetrance is responsible, but it is affected by other factors (called incomplete penetrance).
3) That an even more common recessive gene, again with incomplete penetrance, is responsible.
Any of these theories could be correct, because once you invoke incomplete penetrance, differentiation between theories becomes difficult.

However, for purposes of using this test, the underlying genetic mechanism is not relevant. What you have is a marker that when present indicates a greatly increased risk, and when absent, indicates a greatly reduced risk. It does not matter at this point whether it is predicting a mutation in one of two required genes, a mutation in a dominant gene, or a mutation in a recessive gene. Its applicability is exactly the same.

Question:   If we reduce the M allele frequency significantly, would we have a significant negative impact on genetic diversity in any of the breeds?

Answer:   A gradual reduction of an allele that has about a 30% frequency is not a risk to diversity. Also it is unlikely that all breeders will embrace the test simultaneously. Some breeders will eliminate or greatly reduce the M marker; others will do this to some extent, while others will ignore it. This mix of responses will minimize any impact. Keep in mind that when the genetic defect is found, it will probably have a relatively high frequency, putting the breed in exactly the same situation.

Question:   What about the cost of the test? Why should a marker test that is 80% predictive cost as much as a direct test of the mutation that is 100% predictive?

Answer:   The cost is not based on a differential value to the breeder, but on the costs of providing the service and the cost of research to develop the information to develop the test. VetGen has yet to make a profit on any test it has offered.
 

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