Over 200 genetic mutations (variations, deletions, insertions) have now been associated with the development of clinical disease in the dog and cat. Not all individuals with a disease-causing mutation will develop the disease, and not all individuals that develop disease due to a known mutation will develop the disease with the same disease severity.

With the increasing role of genetics in veterinary medicine, there is increasing desire to use this knowledge to produce healthier pets. Once genetic testing becomes available, counseling a pet owner or breeder on how to use the tests is very important. Once a genetic test has been developed, a breed association may be in a hurry to remove any animals with the mutation immediately from the breeding pool. This may seem to be a good idea, but it can have a significant negative impact on the breed. If the mutant gene is found to exist in 40% of a cat or dog population, a sudden reduction in 40% of the gene pool could dramatically alter the breed. Additionally, due to complicated genetic phenomena noted in many genetic diseases, not all animals that have the mutation will develop a clinical form of the disease. These concepts need to be carefully weighed against the issues of continuing to produce animals that may carry a mutation and could potentially suffer from the disease. Therefore, guidelines for counseling owners about the results of their genetic tests need to be carefully developed. For the breeding animal, recommendations to continue breeding should be based on many factors, including size of the breed association, type of disease, risk that the animals produced will develop disease from the mutation, and severity of the disease. The positive attributes of the animal should be considered.

Here are some general guidelines for counseling owners about genetic diseases.

Genetic Test Results

Negative

This indicates that the individual animal does not carry any copies of the known disease genetic variant (mutation).

Considerations for the individual animal and breeding population: No special considerations, since this animal should neither develop disease nor have the ability to spread disease within the population.

Positive Heterozygous

This indicates that the animal has one copy of the normal gene (wild type) and one copy of the disease genetic variant.

Considerations for the individual animal: If the disease is autosomal recessive, this animal should never develop the disease, so no special considerations are needed. If the disease is autosomal dominant, this animal is at risk of developing disease. However, since this animal carries the disease variant and is at risk of disease development, a patient management strategy includes annual monitoring for signs of disease and considers dietary, medical, or other options. If the disease is X-linked recessive, a male with the disease variant on his X chromosome is likely to develop disease, and a female with the disease variant on one X chromosome is likely to be a silent carrier of disease.

Considerations for breeding: If autosomal recessive, this animal will not develop disease and can be bred to an animal that is negative. This strategy will likely produce both negative and positive heterozygous animals, but neither will develop disease. If the disease is autosomal dominant, a similar strategy for breeding could be considered, and one could breed a positive heterozygous animal to a genotype negative animal. The offspring of this mating (positive heterozygous to a negative) will ideally produce at least some genotype negative offspring, and one of these with the desirable traits of the parents could be selected to replace the positive heterozygous parent in future breedings. This breeding will also produce a few positive heterozygous animals. So this does risk producing animals that may suffer from disease. Therefore, this strategy should be considered with regard to the type of disease that may develop in the offspring.

If the animal is an exceptional animal due to personality, health, intelligence, or other characteristics, one may be more likely to try this approach once or twice in hopes of producing a genotype negative replacement animal. If the disease is X-linked recessive, a male with the mutation on the X chromosome could be bred to a negative female. This will produce both male and females that do not have disease. The male offspring of this mating will not carry the mutation since males cannot pass on their X chromosome to their sons. Female offspring will also be clear of disease; they would need to carry it on both X chromosomes to actually demonstrate the disease. However, importantly, females with a disease variant on one X chromosome will be silent carriers of the trait.

Positive Homozygous

This animal has two copies of the disease variant.

Considerations for the individual animal: Positive homozygous animals have the highest risk of developing the disease. A patient management strategy should be developed that may include annual monitoring for signs of disease and consideration to dietary, medical, or other options.

Recommendations for breeding animals: Since positive homozygous animals carry two copies of the mutation disease, they will certainly pass on the mutation even when bred to a negative animal.

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A large number of diagnostic testing laboratories now offer genetic tests for a number of canine and feline diseases. Samples may be submitted in a variety of forms, including buccal swabs, blood samples in EDTA and semen straws. It is important to understand the type of testing performed. PCR-based sequencing continues to be one of the most accurate methods for testing.

Finally, since these canine and feline familial diseases are complicated with issues that include incomplete penetrance, variable expression, closed gene pools, and variable phenotypes, it is ideal to use a testing service that is closely linked with the investigators that studied and discovered the disease variants and can provide the most expertise in genetic counseling for pet owners. A reasonable consideration is to identify the report of mutation discovery and contact the corresponding author's laboratory to identify the testing facility of choice.