The number of canine genetic tests available to breeders and veterinarians has increased radically over the past 10 years in the wake of new discoveries made by research groups. Following this development, several DNA testing laboratories have restructured their services to move from one-by-one single gene tests to offering multiple disorder or trait tests at once. Such services are typically offered as “combination packages”, “multiplex or panel tests”, or a “smorgasbord” where the consumer picks the desired gene tests. Understandably, this transformation of canine gene testing is raising some concern. How will breed clubs, breeders, veterinarians and kennel clubs be able to cope with the increase in information brought about by the post-genomic era? How should information from comprehensive genetic testing most appropriately be incorporated into overall breeding programs?
Towards personalized pet care through advances in diagnostics
We argue that panel testing of inherited disorders – when carried out and interpreted responsibly, carefully, and sensibly - has great advantages. It not only offers immediate benefits for the individual consumer, but also represents a tremendous leap forward for canine healthcare and genetic research through improved diagnostics and insight into the true distribution of mutations causing inherited disorders across breeds. Any breeder or veterinarian confronted with DNA-testing needs would likely prefer a cost-efficient service that simultaneously provides results for as many known breed-relevant tests as possible with one sampling, analysis and reporting. Any researcher confronted with what appears to be a novel inherited disorder for a breed would likely benefit from a comprehensive testing tool that enables exclusion of already known mutations before embarking on a laborious search for a novel one.
It is evident that some of the most common canine inherited disorders are genetically heterogeneous in nature (i.e., can be caused by any of several different gene mutations, or a combination thereof). As an example, we need multiple tests at once to understand the genetic background of progressive retinal atrophy (PRA) – across pure breeds, in a mixed breed with unknown background, or even within one breed such as the Golden Retriever. Likewise, multiple tests are needed to understand the molecular background of cystinuria, pyruvate kinase deficiency, or ataxia in the Russell Terriers. A panel test, as any DNA test, is particularly beneficial for diseases that are difficult to diagnose with certainty without a DNA analysis, and for disorders ameliorated by appropriately applied early preventive treatment.
Thus, comprehensive DNA testing is an important part of a transition towards predictive, preventive and personalized healthcare also for dogs. However, extensive DNA testing does raise a number of questions for the dog community. How should unexpected findings from panel test screening of hundreds of mutations be handled? More DNA-based results means more need for genetic counseling - whose responsibility is it? Is there a risk that breeding will become overly focused on the results of DNA tests?
Careful and collaborative follow up of unexpected panel test findings provides new insights
Based on a couple of years’ experience with panel testing, we can safely say that it does bring along some novel findings; more specifically, mutation findings in breeds in which the particular mutation had not been previously encountered. In our experience, the reasons for this are 1) shared ancestry and history of the breed with the original breed the mutation was discovered in; or 2) modern-day more recent crossbreeding (inadvertent or conscious). The former scenario is particularly true for ancient mutations such as the ones associated with hyperuricosuria or factor VII deficiency, whose distribution across breeds we are now beginning to understand more comprehensively. The latter scenario is a practical reality of dog breeding that should not be overlooked. Breeders are following the very sensible recommendation to maintain open stud books or crossbreed to maintain the breed gene pool, but at the same time unknowingly bringing in a potential new health problem. Thanks to panel testing, we have observed disorders such as lens luxation and cerebellar ataxia being transferred from one breed to another, and been able to alert breed clubs to the presence of a potential health problem.
No matter the underlying reason for an unexpected panel test finding, it needs to be appropriately handled without leaving the concerned dog owner alone with the information. We have adopted a standard operating procedure where an unexpected finding for the breed is always first confirmed by an independent genetic technology (sequencing). Subsequently, we launch a clinical research program in collaboration with breeders, vets, and researchers, aiming to conclusively demonstrate that the mutation is of clinical relevance also in the new breed (which may not always be the case). In our opinion, it is only after such convincing proof that the mutation should be deemed of relevance for breeding strategies in the new breed. Thus, comprehensive DNA testing needs to go hand in hand with high quality molecular and clinical research, and any laboratory offering a panel testing service should have the readiness for such work to be able to promote dog health most efficiently.
Readiness of multiple parties needed for sensible information management
Related to communication of panel test results, we find that another practical reality is the great variability in genetics knowledge background of the general public, breeders and veterinarians. Understandably, a layman is easily overwhelmed by extensive information presented in geneticist jargon that is often difficult to avoid when dealing with complex phenotypes or uncertain modes of inheritance. We believe in a shared responsibility of genetic counseling, where the testing laboratory certainly plays an important part in informing the consumer about the basic nature of the DNA test and the tested disorder, the immediate consequence of the result for the tested dog, and where to seek additional information. In addition, breed clubs have an overall responsibility for the health of their breed and are strongly encouraged to oversee that the relevant persons in charge have the necessary knowledge background to understand, interpret, and ultimately make recommendations based on genetic information. Finally, physicians practicing human medicine are likely faced with a transition from reactive to predictive and preventive health care in the near future, with some leading health care professionals claiming that it may even be considered malpractice to treat a patient without considering their personalized genomic data. A comparable situation may well apply to veterinarians alike, working in an environment where genetic information already today has direct consequences on who produces offspring with whom. It is highly recommended that we, the dog community, make sure that modern veterinary training provides the necessary background in genetics that is needed for practitioners not to be caught off guard by genetic information or the questions of an adept breeder.
In particular, genetic counseling provided by any party related to panel testing needs to make absolutely clear what the test is actually saying and what it is not saying. Panel testing is a demonstrated powerful diagnostics and research tool from the perspective of a vet or researcher. The regular breeder or dog owner should think of it as a convenient and cost-efficient way of getting as many test results known to be relevant for the breed as possible in one go, while simultaneously advancing breed health- and canine genetics research in a novel way. In the hands of a research-oriented DNA testing lab, a dog’s test results may lead to the discovery of, or even prevention of, a non-evident or emerging health problem. It is important to understand that a panel test is only providing the result for the particular mutations being assayed. For instance, a dog may be clear of all tested PRA mutations, or even all disorder mutations that were tested for. Does this imply the dog is completely healthy and will never ever develop PRA or any other disease? Of course not! There will always be additional unknown gene variants and environmental factors involved in determining disease risk, and no panel test is able to predict everything.
Testing for disorders is important, but do not lose track of the big picture
We should never ever lose track of the overall breeding goal and strategy. It is too easy to focus excessively on what we can measure – be it hips, eyes, or DNA tests – when in reality all of these subareas together with information from other characteristics and conditions form the holistic view we need to best promote dog health. Long before any panel testing, a “trendy test” phenomenon was observed, referring to breeders rushing to eliminate carriers of an inherited disorder from breeding as soon as a novel gene test became available for the breed. This has obvious detrimental effects on the gene pool of the breed. As has been stated by prominent scientists in canine genetics, a test result should not necessarily alter who is bred, but who one is bred to. We advocate sustainable breeding that simultaneously takes into consideration both the overall genetic diversity of the breed, and relevant inherited disorders. In this regard, a panel test provides an efficient tool helping to avoid breeding affected offspring while keeping carriers included in the breeding program. Optimally, animals that would otherwise not have been bred due to fear of a family history of an inherited disorder can be allowed to contribute to the gene pool. As us humans, no dog is clear of disease mutations. Therefore, maintaining and monitoring genetic diversity by pedigree-based statistics and modern molecular genetic measurements is likely to be the only efficient long term solution that prevents enrichment and emergence of new recessive disorders.
In conclusion, responsibly applied and interpreted panel testing of inherited disorders combined with genetic diversity measurement represents a powerful tool for canine health care and breeding. Open collaboration between breed clubs, DNA testing laboratories, veterinarians and researchers is likely to provide the optimal benefit for the health of dogs. Panel testing does raise the need for clear communication of the comprehensive results along with thorough genetic counseling. No breeding selections should be based solely on DNA, but holistically on working towards an overall breeding goal that is beneficial not only for the immediate health of the offspring, but also for the sustainability of the breed as a whole.
Novel possibilities and demands brought about by panel testing
- Cost-efficient testing of several breed-relevant disorders with one sampling
- A tool for informed breeding decisions, when properly interpreted
- Comprehensive molecular diagnostics for veterinary practice
- Discovery platform for canine genetics and breed health research
- A significant step towards predictive, preventive and personalized healthcare
- Enables simultaneous control of inherited disorders and preservation of genetic diversity
- Enables simultaneous insight into inherited traits, breed ancestry and population substructure
- Requires careful and responsible follow-up of incidental genetic findings
- Complex information management related to IT solutions, reporting, and customer communications
- Increased need for genetic counseling to ensure results are interpreted and applied correctly in breeding programs and veterinary practice
- As any DNA test, needs to be viewed as one subpart of an overall breeding decision and strategy