Jerold S. Bell, DVM
Dept. of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA
As practicing veterinarians, we see genetic disease in our patients every day. The hallmark of genetic disease is its predictability, and therefore we have the opportunity to intervene and lessen its impact for our patients. The predisposition to genetic disease is life-long. Therefore, these must be treated as chronic diseases and not just with intermittent treatment during clinical episodes. The opportunity to genetically counsel our clients occurs throughout the pet's life.
On a Client Acquiring a New Pet
If a client asks about adopting or purchasing a new dog or cat, we can discuss breed or mixed-breed phenotypic and behavioral expectations and whether they fit with the client's lifestyle and home environment. Terrier and terrier-type dogs have very different behavioral characteristics than retrievers or shepherds. Long-haired versus short-haired cats and dogs have different grooming requirements.
If the client is purchasing a purebred dog or pedigreed cat, there are breed-specific pre-breeding health screening requirements for the parents. For dogs, these can be found at the OFA Canine Health Information Center (www.ofa.org/breedtests.html). Common genetic disorders and tests for cat breeds can be found on the International Cat Care website (https://icatcare.org/advice/cat-breeds).
The WSAVA Canine and Feline Hereditary Disease (DNA) Test website, hosted by the University of Pennsylvania contains information on all DNA tests available in dogs and cats. You can search by breed, disease, or laboratory. It contains links to the original published article on each disease test, as well as which laboratories run the tests: (http://research.vet.upenn.edu/WSAVALabSearch; VIN editor: link could not be accessed on 5/16/18). This site lists all identified mutations, including rare mutations that may not be present in breeding populations.
Health-conscious breeders are happy to provide official documentation of the results of health screening. In the US, the results of a puppy's parents' health screening can be looked up on the OFA website (www.ofa.org). Many other countries have searchable health testing databases; though there are more for dogs than cats.
Some breeds and mixed breeds (designer or "bred-forrescue" dogs) do not have specific pre-breeding health screening requirements. All parents of purposefully bred litters should have pre-breeding health examinations (musculoskeletal, heart, eye, etc.) and history taken for hereditary disease (allergies, seizures, etc.) to determine their suitability for breeding. Pre-breeding health evaluations should become as routine and commonplace as equine pre-purchase examinations.
In most instances, veterinarians will not be asked for advice by a client prior to a purchase or adoption. When being presented with a new purposefully bred puppy or kitten for examination, the owner should be told to bring all paperwork provided by the breeder, pet store, broker or agent. If evidence of health screening on the parents has not been provided, health test results on the parents may be looked up in online health testing databases.
If health screening results are not available, you can print out the pre-breeding health screening requirements or testable diseases and have the owner ask the breeder for health testing information on the parents. This may be the only way to educate the owner and breeder on the ethical obligation of health screening and health conscious breeding. Selective pressure is the only way to reduce the frequency of genetic disorders in purposely bred dogs and cats. Health-screened parents produce healthier kittens and puppies.
Genetic Counseling in Owned Animals
Veterinarians should be knowledgeable about common disorders with genetic tests, and in what patients they should be run. If parental documentation of genetic testing is not available, certain breeds should undergo genetic testing early in life. For example, patients from breeds with an incidence of von Willebrand's disease should be tested so that measures can be taken to prevent excessive hemorrhage during surgery or injury. Patients at risk of carrying the mdr-1 mutation should be tested before drug treatment. We counsel owners of large-breed puppies to feed lower calorie "large breed growth or puppy" foods to provide for a more uniform growth rate and better joint development. Boxers should be tested while young for the dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) gene. Carriers can be monitored for arrhythmias through life, and when they occur can be put on antiarrhythmic drugs to prevent heart failure.
The expression of some genetic disorders cannot be altered. If a genetic test is available, it should be utilized pre-purchase so that owners are not burdened with predictable genetic disease. However, for owned animals it is a personal decision whether the owner wants to know if their pet has liability of developing a non-treatable genetic condition later in life. These include polycystic kidney disease (PKD) in Persian, Himalayan and related cats, hypertrophic cardiomyopathy (HCM) in Maine Coon and Ragdoll cats, dilated cardiomyopathy (DCM) in Doberman pinschers, and the (poorly penetrant) liability gene for degenerative myelopathy (DM). These tests could also be used to rule out diagnoses in clinical patients with suspected genetic disease.
Dietary recommendations should be offered for identified genetic predispositions such as FUS/inflammatory cystitis in cats, dogs and cats with non-struvite bladder stones, and obese "pre-diabetic" cats. Behavioral counseling and early training recommendations should be offered with breeds or individuals demonstrating aberrant or pathological behaviors.
Based on different modes of inheritance, there are guidelines to preserve breeding lines and genetic diversity while reducing the risk of producing carrier or affected individuals.
In the case of a simple autosomal recessive disorder for which a direct genetic test for carriers is available, the recommendation is to test breedingquality stock, and breed normals to normals, or quality carriers to normal-testing individuals. This prevents affected offspring from being produced. Breeders should be counseled to replace carriers in a breeding program with a quality normal-testing offspring. This will maintain breed quality and diversity.
If a breeder finds that a quality individual tests carrier, many are inclined to remove it from their breeding consideration. This is the wrong decision for the breeder and the breed. The individual dog or cat was already determined to have qualities acceptable for breeding. Genetic testing should be used to increase a breeder's choices, not limit them. Eliminating all carriers of testable disease-causing genes significantly restricts breed genetic diversity. Any quality individual that would have been bred if it had tested normal should still be bred if it tests as a carrier. A genetic test for a simple autosomal recessive disorder should not change who gets bred, only who they get bred to. As each breeder tests and replaces carriers with normaltesting offspring, the problem for the breed as a whole diminishes.
A simple autosomal recessive disorder for which no carrier test exists allows the propagation and dissemination of unapparent carriers in the gene pool.
Carrier risk must be determined based on the knowledge of affected or carrier relatives. These can be visualized through vertical pedigrees on the OFA website, or other health databases. Quality carriers should be replaced with non-affected relatives, and bred to individuals with low carrier risk (depth and breadth of pedigree normalcy). High carrier risk individuals should be bred to low risk individuals. The high risk parent should be replaced in breeding with a lower risk quality offspring. To further limit the spread of the defective gene, the offspring should be used in only a limited number of carefully planned matings, and then should also be replaced with one or two representative offspring. The rest of the litter should be placed in non-breeding (pet) homes. With this mating scheme, you are maintaining the good genes of the line, reducing the carrier risk with each generation, and replacing, not adding to the overall carrier risk in the breeding population.
Autosomal dominant genetic disorders are usually easy to manage. As affected individuals have approximately 50% affected offspring, they should be replaced for breeding with normal relatives. Issues with some autosomal dominant disorders include incomplete penetrance. With these disorders the presence of the defective gene still confers risk of producing affected offspring and should be selected against.
For sex-linked (also known as X-linked) recessive defective genes, selecting a normal male for breeding loses the defective gene in one generation. High carrierrisk females should not be used, as carrier females produce 50% affected sons. Rare sex-linked dominant disorders are managed the same way as autosomal dominant disorders.
Most complex/polygenic disorders, and those with an undetermined mode of inheritance have no tests for carriers, but they do have phenotypic tests that can identify affected individuals. Controlling polygenically inherited disorders involves: 1) identifying traits for selection that more closely represent the expression of disease-causing genes, 2) the standardization of nuisance factors (such as environment) that can limit your selective pressure against the genes, and 3) selecting for breadth of pedigree as well as depth of pedigree as demonstrated by vertical pedigrees.
With polygenic disorders, a number of liability genes must combine to cross a threshold and produce an affected individual. A clinically normal individual from a litter that had one or no individuals affected with a complexly inherited disorder is expected to carry a lower amount of liability genes than an individual with a greater number of affected littermates. This is why it is important to screen both pet and breeding dogs and cats for polygenic disorders. Information on the siblings of the parents of potential breeding individuals provides additional data on which to base breeding decisions.
If an individual is diagnosed with a genetic disorder, it can be replaced with a normal sibling or parent and bred to a mate whose risk of having liability genes is low. Replace the higher-risk parent with a lower-risk offspring that equals or exceeds it in other aspects, and repeat the process.
Genetic tests are extremely useful tools to help manage genetic disorders. Even when there is no test or a known mode of inheritance, much can still be done to reduce the incidence of affected and carrier animals. The use of these guidelines can assist breeders in making objective breeding decisions for genetic-disease management while continuing their breeding lines.
It is distressing when a genetic disorder is confirmed. Veterinarians can make positive and practical genetic counseling recommendations to maintain breed lines and genetic diversity, and improve the overall health of breeds. Each breeder will have their own rate of progress depending on the frequency of the defective gene(s) in their own breeding animals, and which desirable individuals carry liability genes.
With the increasing availability of genetic tests, there is increased risk of misusing and misinterpreting them. There is also the propensity to recommend inappropriate and unnecessarily genetic testing, which can diminish our clients’ compliancy. It is our responsibility to understand the proper use and interpretation of genetic tests to provide appropriate genetic counseling recommendations to our clients.