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.
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with Permission |
