The ease and affordability of access to genomic information, and consequently the number of genetic tests available to breeders and veterinarians, has changed radically over the past 10 years. More than 200 canine and 60 feline genetic variants underlying Mendelian disorders or traits have been described to date.1 When limiting the consideration only to known breed-relevant tests, we are still faced with availability of 5–10 DNA-based disease tests for many breeds. At the same time, public information on the population prevalence of the disease variants targeted by the tests, their relative importance for breed health, and distribution across breeds, is typically incomplete.
In addition to disease testing, genetic information is readily available for companion animals on various conformational and morphological traits, breed ancestry/background, and through DNA-profiling for parentage verification. In general, genetic testing is currently pursued for the most part on the initiative of breeders complying with breed club recommendations or driven by dog owners’ curiosity about their dog’s genetic background. However, genetic diagnostics has the potential to develop into an important supportive part of predictive, preventive, and personalized pet care given adoption of available tools in veterinary medicine.
A recent trend among DNA testing laboratories offering services for companion animals has been the restructuring of services from offering one-by-one single gene tests to providing multiple disorder or trait tests at once as “combination packages,” “panel tests,” or a buffet where the orderer picks the desired gene tests. Although this transformation of genetic testing undoubtedly has benefits for multiple parties in terms of synergistic sampling, sample logistics, analysis, and reporting, it understandably warrants an informed and responsible approach. The scientific foundation and power of comprehensive screening to advance our knowledge on the distribution of disease variants across breeds has been established, with mutation findings in unexpected breeds typically explained by either shared breed ancestry or recent cross-breeding.2 However, high service provider standards of following up on unexpected discoveries through both additional genetic experiments and clinicopathological follow up studies are a necessity.
In more detail, a number of valuable lessons have been learned from our genetic screening studies encompassing more than 100,000 canines representing the general population of both mixed breed dogs and purebreds.3
Risk variants for Mendelian disorders are prevalent in the general dog population, but a subset of around 30 disorders account for the majority of disease allele observations. When screening for 152 known Mendelian disease risk variants in 100,000 dogs, we noted that 40.5% of all dogs (41.8% of mixed breed dogs vs. 32.0% of purebred dogs) carried at least one of the tested disease variants. The maximum number of disease variants carried by any individual dog was five.
Mixed breed and purebred dogs share the same common Mendelian disease variants. The majority of the tested disease variants were found in both populations of dogs studied, and the list of top 12 most common disorders by allele frequency was virtually identical in both groups. Some disorders are likely to have been eradicated from the natural population through selective breeding.
Mixed breed dogs are more likely to carry a genetic disorder, while purebreds are more likely to be genetically affected with one. For the first time, we provide direct genotyping-based evidence for hybrid vigor in mixed breed dogs.
Disease allele prevalence information best serves the community when accessible and updated. We have created an online canine inherited disorder prevalence database, MyBreedData, (mybreeddata.com4) featuring the possibility to search for disease genotype frequencies by breed or by disease. This resource is freely available as a tool to advance breed health research and veterinary medicine.
Mixed breed dogs are likely to display signs of many of the same disorders affecting purebreds. Clinical follow up studies are always needed to confirm mutation effects on other genetic backgrounds. Such additional investigations should ultimately guide how and if a genetic variant should be considered in the overall breeding program. In some instances, comprehensive genotyping across breeds has revealed that the conclusions made in an original study may have been too far-reaching or not generalizable to other breeds or populations, necessitating revision of existing views.
In conclusion, big data and statistics on inherited disorders in the companion animal population are now available, and have the potential to guide DNA testing priorities, breed health research, and breeding selections, while having implications for veterinary education and pet care. The fact that around 2 in 5 dogs carry a genetic variant reported in the literature as associated with a Mendelian disorder emphasizes the need for appropriate genetic counseling in combination with destigmatization of carrier dogs. Sustainable breeding will ultimately need to encompass consideration of both the overall genetic diversity of the breed, and relevant inherited disorders. Up to date knowledge on inherited disorders, their relative prevalence and manifestation in the general dog population, is called for within veterinary education and medicine. Understanding of what information a genetic test result provides, and what information it does not provide, is crucial to ensuring that a result is interpreted and applied correctly in breeding programs and veterinary practice. Even the most comprehensive genetic test is only one subpart of an overall breeding strategy and an animal’s health records. Successful genetic counseling for individuals and populations is ultimately likely to be a cooperative effort involving stakeholders at various levels, such as veterinarians, breed health committees, and national kennel/cat organizations.
1. Faculty of Veterinary Science, University of Sydney. Online Mendelian Inheritance in Animals, OMIA. (http://omia.org/home/)
2. Donner J, Kaukonen M, Anderson H, Möller F, Kyöstilä K, Sankari S, Hytönen M, Giger U, Lohi H. Genetic panel screening of nearly 100 mutations reveals new insights into the breed distribution of risk variants for canine hereditary disorders. PLoS ONE. 11(8):e0161005. doi:10.1371/journal.pone.0161005.
3. Donner J, Anderson H, Davison S, Hughes A, Bouirmane J, Lindqvist J, Ganesan B, Lytle K, Forman O, Fretwell N, Cole C, Lohi H. Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs. Manuscript submitted.
4. My Breed Data Canine Inherited Disorder Prevalence Database. www.mybreeddata.com.