In the Health Section, what does it mean for my dog if he or she has zero, one, or two copies of a variant?

Related terms to better understand your dog’s reports.

Variant: To simplify, the word variant is often used interchangeably with the word mutation.

Genotype: The genetic code related to the variant being present or absent

Phenotype: The physical impact or appearance directed by the genotype

For each test, you have the possibility of receiving the following results: zero, one, or two copies of a variant

Zero Copies: This may also be referred to as being “clear” of the variant. This means that your dog has two healthy copies of the gene sequence being tested and is not at risk for developing the associated disease, at least due to that variant.

One Copy: This means that your dog has one copy of the healthy sequence and one copy of the variant sequence. The likelihood of your dog expressing the disease phenotype because he or she has one copy of the variant depends on the mode of inheritance (MOI) of that variant as described below. The impact of the variant is also influenced by your dog’s breed(s), sometimes referred to as their genetic background. We recommend speaking with your veterinarian to discuss your dog’s results and clinical risk.

Dogs with one copy of the variant will pass the variant to about half of their offspring. Therefore, if you plan to breed a dog with one copy of a breed-applicable variant, testing any potential mates and properly applying those results to your breeding program is recommended.

Two Copies: This means that your dog has inherited two copies of the variant. There may be a potential for showing clinical signs of the disease for which the variant promotes risk. As with one copy, the impact of the variant is also influenced by your dog’s breed(s) and genetic background. We recommend speaking with your veterinarian to discuss your dog’s results and clinical risk.

Dogs with two copies of the variant will pass the variant to all of their offspring. Therefore, if you plan to breed a dog with two copies of a breed-applicable variant, testing any potential mates and properly applying those results to your breeding program is of great importance.

Modes of Inheritance

For diseases that are inherited in an autosomal recessive fashion, it means your dog is thought to need two copies of the variant to potentially express clinical signs.

For diseases expressed in a dominant manner, only one copy of the variant is needed for a dog to potentially express clinical signs.

Codominant and additive in general are used to describe variants in which dogs with one copy of the variant have a different phenotype from dogs with zero or two copies of the variant (although there is a slight difference between the two terms which goes beyond the scope of this article).

For diseases that are X-linked (the variant resides on the X chromosome) male dogs need just one copy of the variant to possibly be clinically affected—as they have only one X chromosome. For recessively inherited X-linked conditions, female dogs require two copies of the variant to possibly be clinically affected. Female dogs who have one copy of a recessively inherited X-linked variant are often referred to as carriers, but they can exhibit signs of disease that range from clinically asymptomatic to fully affected. This is due to a phenomenon known as X-Chromosome Inactivation.

Some variants are described as incompletely penetrant. This means that not all dogs with the potential for clinical disease from the variant will go on to develop clinical signs. It is likely that the effects of these variants are impacted by other genetic and environmental factors. In some cases, we can give you an idea of your dog's individual risk based on the prevalence of the disease in question in your dog's breed, but in many cases, we cannot due to lack of current published research.

Impact of Breed

When determining whether or not a variant is expected to have a clinical impact for a breed, we have taken into account research either published, internal, or otherwise presented by a subject matter authority as our primary criteria. So, while a dog may have the variant associated with a disease (one copy or two copies for dominant variants and two copies for recessive variants), he or she may not be known to be at clinical risk from that variant. 

Based on the available research within the breed or highly related breeds, you may see text similar to the following options: this genetic variant is not likely to increase the risk that your dog will develop this condition; this genetic variant is associated with an increase that your dog will develop this condition; we do not know whether this variant increases the risk that will develop this condition.

Keep in mind that genetic testing is not a clinical diagnosis.

Because genetic testing is an assessment of risk and not a clinical diagnosis, the term at-risk is often preferred to affected when describing a dog based solely on genetic test results. If there is a concern based on genetic test results, we strongly recommend contacting your veterinarian to determine the best steps for testing, treating, and monitoring your dog. You can download and share your dog's results at any time. Embark's team of Veterinary Geneticists are available to speak with you and your veterinarian as well.

 More information on the basics of genetic terminology and what can influence if a dog will develop clinical signs from a variant can be found at https://embarkvet.com/resources/dog-breeders/science-corner-genetics-101/