Clinical Genetic Counseling & Control of Hereditary Diseases
ACVIM 2008
Jerold S. Bell, DVM
North Grafton, MA, USA


The new age of genetic testing and genetic counseling encompasses more than dealing with breeders and breeding animals. The hallmark of genetic disease is the ability to predict it prior to its onset. As many genetic disorders cause preventable morbidity, early diagnosis and treatment is important. As practitioners, we deal with genetic disease every day in our practice in pure-bred, cross-bred, and mixed-breed dogs and cats. The vast majority of our patients are not breeding animals, but they still require genetic counseling for inherited disorders. We counsel owners of large-breed puppies to feed lower calorie foods to provide for a more uniform growth rate and better joint development. We understand the nutritional counseling needs for FUS cats and obese "pre-diabetic" cats. When we do bacterial culture and sensitivity testing, we are genetically testing the bacteria for their antibiotic sensitivities. In the future, we may be able to test bacteria for their ability to develop specific antibiotic resistance; despite their sensitivity based on culture. We now have the ability to do immunohistochemical testing of neoplastic biopsy samples for p53, mdr, Ki67, AgNOR, kit and other genetic markers to fine-tune treatment recommendations and prognoses in individual patients. Mixed-breed DNA tests may assist veterinarians and owners to understand specific disease predispositions, and behavioral traits.

In a clinical setting, genetic tests are necessary to diagnose disorders in pet and breeding animals. Breeds with a predisposition to von Willebrand's disease should be genetically tested ( prior to any elective surgery. These include; Bernese Mountain Dog, Doberman Pinscher, Drentsche Patrijshound, German Pinscher, Kerry Blue Terrier, Manchester Terrier, Papillion, Pembroke Welsh Corgi, Poodle, Scottish Terrier, and Shetland Sheepdog. Breeds with increased frequency of the defective MDR1 gene should be tested early in life ( These include; Australian Shepherd, Collie, Old English Sheepdog, and Shetland Sheepdog.

Genetic Disorders of Pure-Bred and Mixed-Breed Cats and Dogs

It behooves us as veterinarians to become acquainted with the breed-specific hereditary disorders, their modes of inheritance, and available genetic tests. This assists us in our differential diagnoses, and our ability to properly counsel clients. As dogs and cats evolved, they brought their genetic susceptibilities with them. The most common genetic disorders occur in pure-bred, cross-bred, and mixed-breed dogs and cats. The most frequent feline genetic disorder seen in practice is sterile feline lower urinary tract disease (FLUTD), with or without inflammatory cystitis. Burmese cats have a significantly higher incidence of Type II diabetes, although random-bred cats are the most frequently diagnosed with this disorder. The most frequent single-gene feline disorder seen in practice is polycystic kidney disease (PKD), caused by an autosomal dominant gene. This defective gene is present in a high frequency (38% testing positive at the UC-Davis Veterinary Genetics Laboratory) in Persian and Himalayan cats. Due to its dominant inheritance, PKD is not a rare diagnosis in Persian and Himalayan cross-bred or random-bred cats. Other common genetic disorders in cats include autosomal dominant hypertrophic cardiomyopathy in the Maine Coon Cat, Ragdoll, and their crosses (, patellar luxation, and hip dysplasia.

The most common inherited disorders for all dog breeds according to the AKC Canine Health Foundation are: cancer, eye disease (pra, cataracts, glaucoma, etc.), epilepsy, hip dysplasia, hypothyroidism, heart disease, autoimmune disease, allergies, patellar luxation, and bloat. All of these genetic conditions are routinely seen in mixed-breed dogs. Older mixed-breed dogs with hip arthritis have no less a diagnosis of hip dysplasia than a 2 year old pure-bred brought in for hip radiographs. Testing for inherited hypothyroidism (for thyroglobulin autoantibodies at the Michigan State University DCPAH) shows 10.7% of 55,053 mixed-breed dogs to be affected. The average percentage of affected dogs for all pure breeds is 7.5%. This does not tell us that mixed-breed dogs are more prone to autoimmune thyroiditis: More mixed-breed dogs are tested based on clinical signs, versus pre-breeding testing for pure-breds. However, these results show us that this hereditary disorder is seen frequently in both pure-bred and mixed-breed dogs.

There are some defective disease-causing genes that mutated so long ago, that the mutation (and its associated disease) is found in evolutionary divergent breeds. The same ancestral autosomal recessive mutation for the progressive rod cone degeneration (prcd) form of progressive retinal atrophy (PRA) is found in the American Cocker Spaniel, American Eskimo Dog, Australian Cattle Dog, Australian Shepherd, Chesapeake Bay Retriever, Chinese Crested Dog, English Cocker Spaniel, Entelbucher Mountain Dog, Finnish Lapphund, Golden Retriever, Kuvasz, Labrador Retriever, Lapponian Herder, Nova Scotia Duck Trolling Retriever, Poodle, Portuguese Water Dog, Spanish Water Dog, Stumpy Tail Cattle Dog and Swedish Lapphund. This list continues to grow as more breeds are discovered with the same defective gene. The question is not, "Which breeds carried this defective gene during their development", but "Which breeds did not lose this defective gene during ancestral development."

It is also not surprising that prcd-PRA affected dogs (who must receive the defective gene from both parents) have been identified in Labradoodles (Labrador x Poodle crosses), and Cockapoos (Cocker Spaniel x Poodle crosses). Labradoodles are also diagnosed with hip dysplasia, elbow dysplasia, and inherited Addison's disease; all recognized disorders in both parent breeds.

With public demand for healthy pets, our responsibility as veterinary professionals is to offer advice to breeders and prospective buyers. We have no control over randomly-bred (mixed-breed) dogs and (domestic) cats. However, for purposely-bred dogs and cats (both pure-bred and designer-bred), breeders should perform genetic testing for each parent's breed-susceptible disorders. Official test results should be made available to prospective breeders, and the pet and breeding-stock purchasing public. It doesn't matter whether a breeder is a large commercial breeder, or only breeds once. In today's environment, not testing for documented breed-related hereditary disease is irresponsible breeding.

As veterinarians, we should ask for pedigrees and results of parental or early age health testing of pure-bred and cross-bred puppies and kittens on first presentation. If the test results were not provided to the owner, many can be immediately searched in on-line databases like OFA, CHIC, or CERF (see below under genetic registries). A lack of available test results shows that the puppy or kitten was not purchased from a health conscious breeder, and it may be liable to develop genetic disease. We must educate the general public to become informed "consumers" when purchasing puppies and kittens. They should spend as much time researching the purchase of what will become a member of their family for 10+ years, as they do purchasing a home appliance. Breeder health guarantees that provide for replacement of puppies and kittens with genetic disease are often worthless; as few pet owners will be willing to give up a member of their family once an emotional bond has been established.

Genetic Counseling for Breeders

Historically, genetic counseling has ranged from recommendations to not repeat a mating and outbreed, to recommendations to eliminate all relatives of affected animals from the breeding pool. Neither of these two extremes serves the best long-term interest of breeds. Outbreeding can prevent the production of affected animals, but it will propagate and further disperse detrimental recessive genes. The goal of genetic counseling is to effectively manage the spread of defective genes, while preserving the health and genetic diversity of the population.

There are no breeding recommendations that will fit every situation. There are, however, guidelines veterinarians can recommend to preserve breeding lines and genetic diversity while reducing the risk of producing carrier or affected individuals. Protocols for genetic counseling and breeding management of genetic disorders can be based on the known (or unknown) mode of inheritance, and the availability and type of genetic tests.

In the case of a simple autosomal recessive disorder for which a direct genetic test for carriers is available, the recommendation is to test breeding-quality stock, and breed quality carriers to normal-testing individuals. This prevents affected offspring from being produced. The aim is to replace the carrier breeding-animal with a normal-testing offspring that equals or exceeds it in quality. As each breeder tests and replaces carrier animals with normal-testing animals, the problem for the breed as a whole diminishes.

With a genetic test, breeders can positively determine if an individual is a carrier of a defective gene. The typical response of a breeder on finding that their animal is a carrier is to remove it from a breeding program. If a majority of breeders do this, it puts the breed's gene pool through a genetic bottleneck that can significantly limit the diversity of the breed. The goal of genetic testing is to allow the superior genes of a breeding individual to be propagated, even if the animal is a carrier. One defective gene that can be identified through a genetic test out of tens of thousands of genes, is not a reason to stop breeding. If an owner would breed an individual if it tested normal for a genetic disease, then a carrier result should not change that decision.

We know that most individuals carry some unfavorable recessive genes. The more genetic tests that are developed, the greater chance there is of identifying an undesirable gene in your patient. History has shown that breeders can be successful in reducing breed-wide genetic disease through testing and making informed breeding choices. However, there are also examples of breeds that have actually experienced more problems as a result of unwarranted culling and restriction of their gene pools. These problems include: reducing the incidence of one disease and increasing the incidence of another by repeated use of males known to be clear of the gene that causes the first condition; creating bottlenecks and diminishing diversity by eliminating all carriers of a gene from the breeding pool, instead of breeding and replacing them; and concentrating on the presence or absence of a single gene and not the quality of the whole animal. Genetic test results should be used to benefit the overall health of breeds, not to limit it.

For autosomal recessive disorders without genetic tests, breeders can still reduce the carrier risk in their matings. A quality individual that is found to be a carrier can be retired from breeding and replaced with a quality, lower-risk offspring. In this way, the carrier risk can be cut in half. By repeating this vertical mating scheme (breeding once to a low-risk mate and replacing with an offspring), 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. The problem with recessive disorders without carrier tests is the propagation and dissemination of unapparent carriers in the gene pool. Multiple offspring should not be placed in breeding homes. An open health registry that is supported by the parent club makes it easier for breeders to objectively assess the carrier risk of prospective breeding animals. By determining the average carrier-risk for the breeding population, breeders can select matings that have a projected risk that is lower than the breed average. Using relative-risk assessment as a tool, breeders should replace higher-risk breeding animals with lower-risk offspring that are equal to or better than their parents in quality. A negative aspect of pedigree analysis is that it selects against families, regardless of an individual's normal or carrier status. On the other hand, it allows for the objective risk assessment and continuation of lines that might otherwise be abandoned due to high carrier-risk. An example of an open health database and relative risk analysis program is cerebellar abiotrophy in the Scottish Terrier (

Autosomal dominant genetic disorders are usually easy to manage. Each affected animal has at least one affected parent, but it can be expected that half of the offspring of an affected animal will be free of the defective gene. With disorders that cause death or discomfort, the recommendation is to not breed affected animals. To produce the next generation of a line, a normal full-sibling of an affected animal can be used, or the parent that is normal can be used. A problem with some autosomal dominant disorders is incomplete penetrance, where some individuals with the defective gene may not show the disorder. Roughly half their offspring, however, may be affected. If a genetic test is available, this is not a problem. Otherwise, relative-risk assessment can identify which individuals are at risk of carrying incompletely penetrant dominant genes.

For sex-linked (also known as x-linked) recessive defective genes, selecting a normal male for breeding loses the defective gene in one generation, regardless of his relationship to affected and carrier relatives. Carrier, affected, or high risk females should not be used, due to the high risk of producing affected male offspring. If a male is affected, he would have received the defective gene from his carrier mother. All of his daughters will be carriers, but none of his sons. Without a test for carriers, you can use relative-risk assessment to breed him to a female that is at low risk of being a carrier. This prevents affected offspring, and a quality son can be selected for replacement. Rare sex-linked dominant disorders are managed the same way as autosomal dominant disorders. The difference is that affected males will always produce all affected daughters.

Most complexly (polygenic) inherited disorders have no tests for carriers, but do have phenotypic tests that can identify affected individuals. These disorders require knowledge of the affected or normal status of full-sibs to prospective breeding animals. Individuals whose siblings are normal and whose parents' sibs are normal have the greatest chance of carrying a low genetic load for the condition. This breadth of pedigree analysis is more important than normalcy in the depth of pedigree (parents and grandparents only.) Affected individuals can be replaced with a normal sib or parent, and bred to a low-liability mate. Breeders can replace the higher risk parent with a quality, lower risk offspring, and repeat the process. For disorders without a known mode of inheritance or carrier test, breeders should be counseled to use the same control methods as with polygenic disorders.

It is distressing to breeders when we confirm a genetic disorder. As veterinary professionals, we can offer positive and practical genetic counseling recommendations to maintain breed lines and genetic diversity, and improve the overall health of breeds. The total elimination of defective genes will probably be impossible for most breeds. The use of these guidelines can assist breeders in making objective breeding decisions for genetic disease management, while continuing their breeding lines. The individual breeder can use genetic tests to; 1) identify carriers, 2) work to breed away from the defective gene(s), and 3) ensure (through testing) that the defective gene(s) is not reintroduced in future matings. 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 are carriers.

Our Role with Genetic Registries

There are several genetic registries that have been established to assist breeders and owners with genetic disease control. The Canine Eye Registry Foundation or CERF ( is a closed database showing only normal eye examination results by ACVO boarded veterinarians. The Orthopedic Foundation for Animals (OFA: has semi-open registries for hip dysplasia & Legg-Perthes disease, elbow dysplasia, autoimmune thyroiditis, congenital cardiac disease, patella luxation, deafness, and other genetic disorders. It is only through the open reporting of affected dogs and cats that knowledge of disease risk can be identified through the test results or health status of close relatives.

It is important that as veterinarians we encourage open reporting of health results by counseling breeders to initial the boxes for open disclosure of test results on the OFA submission forms. The days of stigmatizing conscientious, health-testing breeders who have produced dogs or cats with hereditary disease are gone. No one wants to produce affected offspring from their matings, and no one should be blamed if this occurs (unless the breeder is not doing the recommended health testing).

The Canine Health Information Center or CHIC ( is a portal into the OFA health database that has been established by the AKC Canine Health Foundation and the Orthopedic Foundation for Animals. National parent clubs determine the testable genetic disorders for their breed. (For example: hip evaluation, CERF examination, and thyroid testing.) Owners and breeders can search online for dogs in the CHIC database, and view their test results. If a dog completes the recommended testing panel, it receives a CHIC number regardless of whether it passes all of the tests. CHIC is about health consciousness, not health perfection. As more testable disorders are identified, few dogs will be normal for all tests.

If a client is contemplating breeding their dog, they can look up the recommended genetic tests to perform in their breed. Veterinarians can also assist prospective breeders by looking up and discussing the genetic disorders, recommended genetic tests, and appropriate age for testing. Prospective breeding dogs (in either pure or cross-breeding) can be researched, and their genetic test results, as well as that of their close relatives can be studied.

Open registries require an atmosphere of cooperation and understanding between breeders, for the benefit of the breed. Breeding practices do not cause defective genes. If breeders are reluctant to identify affected individuals, then the usefulness of open registries will be limited.

Breeders are the custodians of their breed's past and future. "Above all, do no harm" is a primary oath of all medical professionals. Genetic tests are powerful tools, and their use can cause significant positive or negative changes. Breeders should be counseled on how to best utilize test results for the best interests of the breed. Breeders, veterinarians, and breed organizations must educate the general public of the need to check for health testing in their dog and cat purchases. As this happens, the overall genetic health of purposely-bred dogs and cats will improve.


1.  2007 Tufts' Canine & Feline Breeding and Genetics Conference

Speaker Information
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Jerold Bell, DVM
Tufts Cummings School of Veterinary Medicine
Enfield, CT

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