Pet-Specific Care for the Veterinary Team. Группа авторов
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chronic disorders, such as diabetes mellitus, osteoarthritis, atopic dermatitis, and others (see 9.4 Standards of Care and 9.6 Care Pathways). However, for many conditions, treatments are customized to the needs of a particular patient. For example, for a pregnant English bulldog, natural delivery may not be possible and cesarean section is often needed. Avermectins might be considered for the management of some conditions, but should be used only cautiously in animals with multidrug resistance (MDR1) genetic mutations.
1.3.6 Genetic Testing and Personalized Care Plans
With pet‐specific care, the goal is to be proactive and address potential issues at the earliest possible opportunity, preferably when problems are still subclinical. DNA testing can be very useful for this purpose, as it can be run very early in life, even as early as 1 day of age (see 3.4 Predicting and Eliminating Disease Traits).
Genetic testing is a useful tool as long as veterinary teams have realistic expectations. The purpose of genetic tests is not necessarily to confirm a diagnosis, but to understand risk factors that could be relevant for an individual pet, even issues that may develop much later in life [4]. So, it is extremely important that veterinary team members understand the difference between association and causation when it comes to such testing.
The vast majority of DNA tests are not absolutely predictive because any one variant detected may not actually be causing the disease in its entirety (see 11.3 Heritable Health Conditions – By Disease). Most often, they just indicate suspected “risk” based on the statistical association of a variant to clinical disease, and it is up to the veterinary team to put such risks in perspective. For example, the skin condition dermatomyositis is often described as being autosomal dominant with variable expressivity (more on this term later), and confirmation of the diagnosis in affected individuals (usually collies, Shetland sheepdogs and their crosses) is based on biopsy. There are at least three different genetic variants “associated” with dermatomyositis risk, and when considered in aggregate, pets can often be classified as high risk, moderate risk, and low risk for developing dermatomyositis. This can be extremely useful for counseling owners of at‐risk pets, even if the predictive ability is not absolute. For some conditions in which there is genetic risk, there can also be future testing indicated. For example, a pet that has a relevant glaucoma variant detectable on genetic testing (in a breed at risk for this variant) doesn't mean that the pet will necessarily develop glaucoma, but it does suggest that further glaucoma screening by periodically evaluating intraocular pressure (IOP) is warranted for consideration. Based on the breed, a personalized care plan can incorporate such testing at appropriate intervals.
In most instances, it is practical to perform genetic screening at about 12 weeks of age. At that time, the pet should be well into vaccination and parasite control protocols, and hopefully enrolled in pet health insurance. Once again, the goal is not to try to diagnose disease in a healthy puppy or kitten with such screening, but to help prepare a risk profile for the animal so that pet‐specific recommendations can be made regarding prevention and early detection programs. For example, knowing a pet's multidrug resistant (mdr1) genetic status can help inform whether certain medications might be problematic if administered. Knowing the genotypic status for vWD can prove very useful if surgical intervention is being considered (including neutering). If veterinary teams consider that the point of genetic testing is to better appreciate potential risk, they will be able to relay more appropriate information to pet owners, and determine what future screening should be taking place in the personalized care plan.
1.3.7 Putting DNA Testing in Perspective
Whether a practice decides to embrace the concept of genetic testing depends on its strategy for delivering healthcare. There is no doubt that more validation is needed in both human and pet genetic health screening, but that doesn't negate the real value in providing such a proactive resource for pet owners.
When it comes to matching DNA from an individual with the likelihood of disease development in the future, it very much depends on the specificity of the genetic variant being measured, and the individual being tested. That's why it takes a veterinary team to help interpret DNA test results, counsel pet owners accordingly (see 3.8 Genetic counseling), and develop a relevant personalized care plan.
Part of the reason that disease detection is not simple is that diseases and traits can be influenced by a variety of different genes, as well as environmental factors. Atopic dermatitis (environmental allergy), for example, is a skin condition that tends to run in families and there are definite breed predispositions, but that doesn't mean that any one DNA test developed will be able to predict onset with any certainty in all pets and all breeds. The body has a lot of redundant systems in place, so even if there is a genetic issue somewhere, it may be possible for the body to compensate through mechanisms elsewhere. Another important point to consider is that genes themselves don't cause diseases. Genes provide the blueprint for creating proteins, and it is typically defective and poorly functional proteins that lead to the clinical picture that we interpret as disease … often with significant environmental influences.
At this point in time, there are a few hundred genetic variants known to affect the health of pets, but new associations are being uncovered on a regular basis. The important thing to remember with such testing is that the most predictive tests will be for medical conditions controlled by a single gene pair (such as vWD type I in the Doberman pinscher, progressive retinal atrophy‐rcd1 in the Irish setter, or ichthyosis‐A in the golden retriever). The vast majority of diseases seen in pets (such as atopic dermatitis, heart disease, diabetes mellitus, obesity, periodontal disease, seizure disorders, etc.) actually have a more complicated pattern of inheritance, and may involve multiple genes as well as environmental influencers, and genetic tests developed for these types of conditions should be expected to be less predictive, even if they still contribute useful information [4]. Even for conditions such as hip dysplasia, heritability is important, but environmental influences often have more impact on clinical expression of the disorder than does genetics (heritability ~0.25). Genetic variants may also have some association with disease in one breed but not necessarily in others and this is not a fault of the testing, but just a reality of pet‐specific care and breed‐specific risk.
Because of the complexity of biological systems, just because there is a genetic mutation that leads to a poorly functional protein doesn't mean that the animal will definitely develop disease. We often describe this as penetrance, the likelihood that a given mutation in an animal will result in clinical disease. Not surprisingly, we don't have enough of this information for many genetic tests, nor for those tests in different breeds. Yet another form of variation is known as expressivity. This refers to the variability in clinical presentation that can be seen in individuals, with some animals with the same genotype being more severely affected, and others less so.
Part of the complexity of such testing is also a great opportunity for veterinary teams. If genetic testing didn't require any expertise or interpretation, there would be little reason for pet owners to want to work with veterinary teams to keep their pets healthy. It is this ability to counsel and coach that makes the veterinary team critical to the success of such programs, and to the evidence‐based creation of personalized care plans.
1.3.8 Putting It All Together
The personalized care plan is just a customized maintenance schedule that helps pet owners see the type of veterinary intervention that is anticipated over a pet's lifetime (see 6.4 Creating a Pet‐Specific User's Manual). Part of that schedule will be based on life stages (see 1.2 Providing a Lifetime of Care); those life stages should reflect the pet's breed or, in the case of mixed‐breed animals, their