Introduction to MyDogDNA panel testing of canine inherited disorders and reporting of the test results

Approximately 600 inherited disorders and traits have been described in dogs. Currently, around 160 of these can be tested for due to mutation discoveries made by, and single-gene tests developed by different canine genetics research groups. MyDogDNA provides the first available panel testing concept combined with a research approach that helps breeders and researchers study the presence and distribution of known inherited disorders across dog breeds, while simultaneously providing any dog owner with a possibility to get results for the tested disorders known in their breed. I thought it would be best to introduce the MyDogDNA test panel and the reporting of the disorder test results by answering the most common questions asked by dog owners.

How do inherited disorders manifest in dogs?

The majority of canine inherited disorders follow an autosomal recessive mode of inheritance. Typically, this means that a dog needs to inherit two copies (one from its dam, and one from its sire) of a mutated gene form associated with a disease in order to manifest the condition. This also means that a dog can carry a mutated gene form in its DNA without ever actually showing any symptoms of the disease. However, once two dogs that are both carrying the same mutated gene form are mated, puppies affected by the disease can be born.

Many canine inherited diseases are very common due to the high number of carriers within the breed. This enrichment in turn is a reflection of multiple genetic bottlenecks in the population history, such as breed formation from a limited number of founders, inbreeding, and overuse of popular sires in breeding.

In addition to the recessively inherited diseases, there are other modes of inheritance as well. Some disorders follow an autosomal dominant mode of inheritance, where one mutated form of the gene is enough to cause the disease. Yet other mutations reside on the sex-determining X-chromosome, which means that the disorders they cause follow so called X-linked inheritance.

It is also important to realise that not all disorders are caused by individual mutations in single genes. Many common health problems in dogs, such as hip dysplasia and several forms of epilepsy seem to be polygenic in nature. This means that their onset is triggered by the combined effects of multiple genetic variants or gene forms together with predisposing environmental factors. Such genetic risk variants that increase genetic susceptibility to certain conditions have been identified. However, many of these variants are very frequent within breeds while increasing disease susceptibility only moderately. Therefore, development of genetic testing for polygenic conditions, and application of such information to sustainable breeding selections in practice, is still a focus of ongoing research.

How does panel testing of inherited disorders work in practice? Is it a scientifically accepted testing method?

Panel testing of genetic mutations has been called for as a next generation testing concept that would finally enable cost-efficient screening for the multitude of known hereditary disorders (e.g., Slutsky et al 2013). The MyDogDNA testing concept relies on a custom developed micro array technology, combined with a PCR (polymerase chain reaction) product analysis that enables a direct assessment of mutation sites in a dog’s DNA. All test results are subjected to careful manual inspection and quality control by the MyDogDNA research team. Moreover, each mutation site is assessed up to three times independently to ensure high quality results. In addition, careful sample type-, and test-retest validations of the panel have been carried out by the research team. 

How are the results of the disorder tests reported?

Reporting in the MyDogDNA panel analysis follows the conventional protocols for autosomal recessive, autosomal dominant, and X-linked disorders. Thus, the results of the included individual tests are reported in the same way as if the tests had been carried out separately. As an example, for a typical recessive disorder a dog that does not have any copies of the investigated disease mutation in its genome is reported to be Clear. A dog carrying one mutated gene copy is reported to be a Carrier, which is also indicated by a yellow flag  in its list of results. An Affected dog carries two copies of the mutated gene form, and the test result is indicated by a red flag . We also show the actual genotype for the convenience of dog owners interested in genetics. Please note that an Affected test result does not always mean that a dog will also manifest a condition even though it is genetically susceptible to it.

Our research team is available for genetic counseling and further help and can be contacted by email: info@mydogdna.com.

Does the MyDogDNA test panel enable discovery of new disorders in my breed?

Yes, it is possible that the MyDogDNA test panel helps us find some of the tested mutations also in breeds in which they have not been previously encountered. However, whether these mutations actually manifest similarly and cause the same disease also in the additional breeds always becomes a topic of further scientific investigation. That is why you would see a magnifying glass icon  in your dog’s Tested Genetic Disorders report. The icon means that the MyDogDNA research team initiates an active study aiming to confirm the genetic presence of the mutation within the breed and to obtain more information on its frequency and distribution. The study then continues on to clinical characterisation of genetically affected dogs in collaboration with veterinarians and researchers. Our first step is always to contact the principal investigator of the research group that originally discovered the gene mutation in order to credit their original work in characterising the disorder.

The collaborative characterisation that follows a new discovery made by the MyDogDNA research team is essential before it can be stated that a mutation is relevant for the additional breeds, and that it should be taken into consideration in breeding selections. Because of the rigorous validation process and the need for additional scientific work, it is very hard to give a precise time frame for when a new test and its results can finally be released in a dog’s report. At times, it may even be necessary to temporarily withdraw a test pending investigation and recruitment of additional dogs to study. Once the clinical characterisation has been completed, results for a novel breed-validated test are ready to be released to the dog owner.

I know there are other available gene tests for my breed but these are not included. Why is that?

First, it should be noted that efforts of making a panel screen for genetic health as comprehensive as possible are complicated by licensures and patents aiming to restrict the use of certain tests. Second, the technical validation process behind a panel analysis that allows us to simultaneously test for several mutations is very long. For any genetic disorder, it requires verified samples from both carriers and affected dogs, as well as controlled repetition of each test. If you notice that a test that you would need for your breed is missing, you can help us have it included by sending us samples of dogs that already have either a carrier or affected test result from before. Moreover, samples of dogs diagnosed with or suspected to have a genetic condition would be extremely valuable for research.  Please don’t hesitate to contact our customer service at info@mydogdna.com.

 

Slutsky J., Raj K., Yuhnke S., Bell J., Fretwell N., Hedhammar A., Wade C., Giger U. A web resource on DNA tests for canine and feline hereditary diseases. Vet J 2013; 197(2): 182-187