Rochelle Jensen BVSc MS Dipl ACT
Genetic testing of companion animals is gaining momentum, and scientific advances have markedly improved the accessibility, affordability, and reliability of genetic tests for pets. While many clients enjoy using genetic tests to identify the breed ancestry of their mixed-breed dogs, there are several disease conditions affecting pets in which a heritable component has proven significant. Over 850 health traits in dogs and over 400 in cats can now be tested, and this offers veterinarians an avenue for genetic counselling and improved patient monitoring and intervention strategies.1
This article will arm veterinary professionals with knowledge of the basic principles of genetic testing, sample collection, reliable database information, test result interpretation, and recommendations for clients.
Genetic tests are becoming commonplace and have successfully been used to decrease the frequency of heritable conditions within a breed.2 An understanding of the basics of genetics and the science that underlies genetic testing can help with test interpretation and ensures appropriate applications in a clinical setting.
Most genetic tests are based on Mendelian genetics—those that are controlled by a single gene—which describes traits that are inherited in a recessive or dominant pattern.3 Recessive heritable conditions are those in which the pet must carry two mutant copies of a gene (one gene inherited from each parent) to develop the disease.3 Dominant heritable conditions are those in which the pet can develop the disease when carrying only one copy of the mutant gene.3
Genetic testing is often complicated by more complex inheritance patterns. For example, sex-linked conditions—genetic conditions that are linked to the X chromosome – will result in a male carrying the mutant gene almost always developing the disease, while a female may or may not be affected depending on whether she carries one or two copies or whether the condition is dominant or recessive.
While Mendelian genetics helps us understand inheritance patterns, veterinarians must also take into consideration epigenetic factors, complex modes of inheritance, and disease penetrance.1,3
Penetrance represents the portion of pets who test positive for a genetic condition that actually develop the disease. A classic example of complete (100%) penetrance is polycystic kidney disease (PKD) in Persian and Himalayan cats. The mode of inheritance is autosomal dominant; therefore, cats suffer PKD when there is only one copy of the mutant gene.4 Cats that carry two copies of the gene generally die in utero.5 Diseases with 100% penetrance pose less of a challenge in formulating recommendations, but conditions with lower penetrance complicate predictions of disease outcomes. Ideally, the company providing genetic test results should report the penetrance of the condition being tested, but this is not always the case.
The literature is vast with information about inheritance patterns of diseases, but an excellent and comprehensive resource is the Online Mendelian Inheritance in Animals (OMIA) website. The site is co-authored by Prof Frank Nicholas and Associate Prof Imke Tammen from the University of Sydney, Australia, and contains information on the genetic diseases, the breeds affected, the mode of inheritance, and all relevant references in a number of different species, including cats and dogs.
In an ideal world, owners would consult with veterinary professionals to determine optimum tests, testing methods and sampling techniques, as well as decide the most appropriate laboratory to send samples for analysis.
However, many companies offer genetic testing for pets, marketed at pet owners on the internet. Owners are able to collect samples and submit them to the laboratory without the guidance or help of a veterinarian. In this instance, the veterinarian’s role in genetic testing moves to helping owners interpret the results of genetic tests and subsequent counselling regarding the health management of the affected pet.
Because different laboratories have differing requirements for sample submission, it is recommended to contact the testing laboratory to determine their recommendations. Common samples include buccal swabs, blood samples in EDTA, semen straws, and plucked hair samples. The quality of the sample submitted can have a significant effect on test results. Buccal swabs and plucked hair samples most frequently return reports of “insufficient DNA”. If clients are submitting samples, they should be instructed to wipe the inner cheek thoroughly to harvest buccal cells rather than saliva, and hair plucks must be numerous and include hair plugs to ensure sufficient DNA.
Laboratories can perform a large number of tests on any breed. Choosing which tests to perform on a pet, however, requires careful consideration to optimise the quality of information presented for subsequent evaluation.
Credible breed organisations, such as the Canine Health Foundation, contain valuable resources that can guide such decisions. Additionally, the Canine Health Information Centre (OFA) is a website that allows you to search by breed and find recommendations on breed-specific testing (note that recommendations are not limited to genetic testing). Some other breed organisations can provide a searchable database with similar guidelines.
Genetic testing panels are not regulated, and no consensus quality control guidelines exist.3 It is recommended that clients only submit samples to laboratories that are endorsed by the researchers who performed the work associated with the genetic disease, universities, or well-known, credible veterinary laboratories.
PennGen is a database funded by the World Small Animal Veterinary Association and it provides lists of many laboratories around the world. It is a good starting point for both veterinarians and clients, allowing search by genetic test, breed, or clinical signs. Additionally, UCDAVIS and Wisdom Health provide information on the mode of inheritance and, in most instances, provide genetic counselling services. As mentioned earlier, veterinarians should enquire with the testing laboratory chosen about sample collection preferences and ask what information and services are provided before deciding where to submit samples.
If a heritable condition occurs with highly frequency within a breed, elimination of carriers and breeding away from it entirely can create a genetic “bottleneck”, increasing the frequency of other undesirable traits within a breed.2 If desired, a more practical approach may be to continue to breed carrier animals, but only to animals that have tested negative, leading to a gradual reduction in unwanted genetic mutations over consecutive generations. The general guidelines listed in Table 1 can help provide recommendations for clients. This table should be used together with test result recommendations and, where appropriate, clinical exam and diagnostic findings.
| Test result | Consequence for individual animal | Recommendations for breeding |
| Negative/wildtype | The pet does not carry the mutation and is unlikely to develop the disease. | The pet will not pass the mutation to offspring. |
| Positive heterozygous | The pet carries a single copy of the mutation. If the disease is autosomal recessive, the pet will not likely develop the disease. If the disease is autosomal dominant, the pet is at risk of developing the disease. Implement a patient monitoring strategy that depends on the genetically linked disease. If the disease is X-linked recessive, males are likely to develop disease, whereas females are likely to be silent carriers. | Autosomal Recessive Breed to animals that are negative for the mutation. Offspring will be either negative or positive heterozygous. Autosomal Dominant If the animal is exceptional regarding other traits, this animal could be bred to a pet that is negative for the mutation. This will result in one in two offspring that are negative for the disease. Offspring that are negative for the mutation can replace the positive heterozygous parent in the breeding programme. X-linked Disease Males who carry the mutation can be bred to females that are negative for the mutation. Sires can be replaced by their sons who will be free of the mutation because males cannot pass their X chromosome to their sons. |
| Positive homozygous | The pet has two copies of the mutation. This pet is at high risk of developing disease. Implement a patient monitoring strategy that depends on the genetically linked disease. | The pet will pass the mutation to all offspring. The decision to breed should be based on the disease penetrance, severity, and positive traits of the pet. Generally, breeding is not recommended. |
While genetic tests provide a useful assessment of a pet’s genotype, they only reflect disease risk. Results must be interpreted with an understanding of the penetrance of the disease and an appreciation that our knowledge of how genetic variants relate to disease outcomes across different breeds is still developing.3
Many heritable disorders have not been well characterised, and Mendelian genetics—a focus in this article—is perhaps over-simplistic, because it suggests a single mutant gene is responsible for a disorder, which is not always the case. Diseases with complex modes of inheritance, such as canine hip dysplasia, cannot be predicted using genetic testing. Complex genetic diseases often rely on the effects of numerous gene variants, and environmental factors such as diet and exercise can contribute to disease outcomes.6,7
Testing for heritable diseases has proven beneficial in reducing the frequency of heritable diseases, but elimination is unlikely. Accurate testing is currently available for only a proportion of heritable conditions, and there remain several autosomal and X-linked recessive disorders in which cloning and characterisation of the gene profile have not yet been established.6 Further, it is common that animals within a breed, having similar clinical signs and testing results, may have more than one spontaneous mutation in the same gene, making accurate diagnosis challenging.6
Knowledge of genetic disorders has increased exponentially over the past two decades and our understanding of their modes of inheritance will continue to do so at a rapid rate. Veterinary professionals play an essential role in guiding breeders’ and pet owners’ decisions regarding their pets or breeding programme and, therefore, must maintain a sound understanding of genetic testing. Ensuring continued support of credible laboratories and making recommendations based on an awareness of the benefits and limitations of genetic testing will ensure that the frequency of mutant genes reduces gradually over time, improving health outcomes for pets with no unnecessary detriment to individual animals.
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