Responsible Breeding and Management of Genetic Disease
Jerold S. Bell, DVM
Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine
North Grafton, MA, USA
Breeders and Breeding
Breeders of dogs and cats desire to produce the best with their matings. However, breeding has become more complicated today, and more people with intact dogs and cats are becoming "breeders". Understanding breed characteristics, historical selection parameters, and the continuous evolution of health testing has not been as important in the development of today's breeders. It is up to all veterinarians, breeders, and breed associations to educate prospective breeders on these aspects to promote healthy breeding practices for dogs and cats.
Adding to the complexity of breeding is the expansion of planned cross-breedings (designer breeds) to produce offspring. Recently this has become more of a factor in dog breeding than cat breeding, but it does occur in both. Therefore, the discussion is no longer between pure-bred and cross-bred, but between purposely-bred and random-bred dogs and cats.
There is a general misconception that mixed-breed dogs and cats are inherently free of genetic disease. This may be true for rare, breed-related disorders; but the common genetic diseases that are seen across all breeds are seen with the same frequency in mixed-breeds. A mixed-breed dog with hip arthritis has no less a case of hip dysplasia than a pure-bred dog. The only difference is that conscientious breeders test and label their dogs as dysplastic prior to the onset of clinical signs. I do not see a difference between the relative frequencies of old pure-bred dogs versus old mixed-breed dogs with hip arthritis requiring arthritis pain medication.
Testing for inherited hypothyroidism (for thyroglobulin autoantibodies by Michigan State University) shows 10.7% of 55,053 tested 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. However, these results show us that this hereditary disorder is seen frequently in both pure-bred and mixed-breed dogs. To those that feel that this disorder is not genetic, we look at the historical breed predilections for the disorder. Those breeds with the highest genetic propensity for autoimmune thyroiditis remain high over the years (example: 31.4% of English Setters tested), and those breeds with the lowest propensity remain low (example: 1.1% of French Bulldogs). Selection based on thyroid testing (and in the future direct genetic tests for liability genes) should reduce the frequency of this disorder.
In cats, the most frequent genetic disorder seen in practice is feline lower urinary tract disease (FLUTD), also known as feline urological syndrome (FUS). This genetic disorder affects the metabolism of normal levels of magnesium and other minerals in the diet, causing urinary crystals, bladder and urethral irritation, and secondary infection. This disorder occurs in pedigreed and random-bred cats with equal frequency. The most frequent single-gene 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 also seen in Persian and Himalayan cross-bred or random-bred cats, and is not a rare presentation in clinical practice. Other common genetic disorders in cats include hypertrophic cardiomyopathy (where direct genetic tests are available for 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, epilepsy, hip dysplasia, hypothyroidism, heart disease, autoimmune disease, allergies, patellar luxation, and renal dysplasia. With the exception of renal dysplasia, all of these genetic conditions are routinely seen in 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 being diagnosed with hip dysplasia, elbow dysplasia, and inherited Addison's disease; all recognized disorders in both parent breeds.
So, if breeders desire to produce the best with their matings, the basic question in dog and cat breeding becomes, "Who is a reputable breeder?" For purposely-bred dogs and cats (both pure-breeding and mixed-breeding), it is those breeders who perform genetic testing for 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 diseases is irresponsible breeding.
Responsible breeding also involves knowledge of how best to use the results of genetic testing. For pure-breeds there are concerns about the breadth of the available gene pool and genetic diversity. Genetic test results should be used to benefit the overall health of breeds, not to limit it. A discussion of these issues, and breeding recommendations for genetic disorders based on different modes of inheritance are included in the 2007 Tufts' Canine & Feline Breeding and Genetics Conference poster abstract; Genetic Testing and Counseling: A Trojan Horse for Dog and Cat Breeds?.
Genetic Test Results and Genetic Registries
For direct genetic tests, official test results of the parents, and/or the offspring (tested prior to placement) should be made available to prospective breeders or purchasers of pet or breeding dogs and cats. For some breed associations, the results of genetic testing are available in on-line, publicly accessible databases.
For disorders where there is no direct genetic test available, the knowledge of phenotypic test results (for affected, or carrier status if possible) should be made available in open health database registries. For most of these 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.
The Orthopedic Foundation for Animals (OFA: http://www.offa.org/) maintains semi-open health registries for testable genetic disorders of dogs and cats. Applications for all of the hereditary disorders in their databases include a check-off to openly report ALL test results; both normal and abnormal. For many breeds of dogs tracking hip dysplasia for example, over one-third of the applicants check the box for open reporting. It is important that as breeders and veterinarians we encourage open reporting of health results. 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). It should be everyone's goal to produce healthy offspring, but this is not possible if the only available health information is about normal dogs and cats, but not abnormal dogs and cats. Once the majority of owners are initialing the box for open reporting, the OFA can change it to a check-off box for not reporting abnormal test results.
The Canine Health Information Center (CHIC: www.caninehealthinfo.org) was established by the AKC Canine Health Foundation and the OFA to assist breeds with managing breed-specific genetic disorders. The AKC national breed clubs determine the recommended testable disorders for the breed (whether tests of the phenotype or the genotype). If an owner 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 recommended genetic tests for the breed. 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.
The benefit of the CHIC system is that dogs gain CHIC certification by completing their health testing, regardless of their test results. CHIC is about health consciousness, not health perfection. As more tests for defective genes are developed, every individual is likely to carry some deleterious genes.
Veterinarians 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 to their clinics. If the test results were not provided to the owner, many can be immediately searched in on-line databases like OFA or CHIC. 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. The general public must be educated 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 home appliances. 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.
Example: Cerebellar Abiotrophy (Ataxia) in Scottish Terriers
The Scottish Terrier Club of America (STCA) has provided all of the tools necessary to determine genetic risk of carrying the defective gene causing the autosomal recessive genetic disorder cerebellar abiotrophy (CA), or for producing affected puppies. CA is a degenerative neurological disease that causes slowly progressive incoordination from several months to several years of age. The defective gene is old, and widespread in the Scottish Terrier gene pool worldwide.
The STCA has an area on their website entitled CA Central (www.stca.biz/GrandCentral/) where a list of all confirmed CA affected dogs and their pedigrees is listed. The club maintains an on-line searchable pedigree database (www.stca.biz/pedigrees/) that includes identification of all dogs with obligate CA risk. They also have a relative risk analysis calculator in CA Central that allows breeders to calculate the CA carrier and affected risk of dogs and of proposed matings.
The STCA has funded several studies to identify the autosomal recessive defective gene causing CA, and its members and breeders hope to some day have a genetic test for carriers. However, CA Central allows their breeders to minimize their current risk of producing Scottish Terriers affected with cerebellar abiotrophy, and reduce the frequency of the defective gene now, while waiting for a genetic test to be developed.
Health testing and the knowledgeable use of test results is now an important requirement for responsible breeding. 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.