Tufts' Canine and Feline Breeding and Genetics Conference, 2009

Responsibility; noun. Duty, obligation, burden

What is the responsibility when someone decides to breed two cats or two dogs together to produce a litter? Everyone knows that genetic disease can occur in any animal. A dog or cat with genetic disease suffers morbidity and/or mortality. For most genetic diseases, we know how to either prevent their occurrence, or at least lessen the possibility of producing offspring with genetic disease. This can occur through the genotypic testing of the parents (identification of parents carrying liability genes for genetic disease), phenotypic testing of the parents (identification of parents affected with genetic disease), or pedigree analysis (identification of carrier risk based on the knowledge of carrier or affected relatives).

Simple Mendelian (one gene pair) disorders with a direct genetic test are absolutely preventable. All that it takes is testing the parents prior to making breeding decisions. Most genetic disorders cannot be absolutely prevented. They have complex, multi-gene inheritance, and liability genes have not been identified. However, for most of these inherited disorders, a method of diagnosing affected individuals is documented. It is also documented which breeds have a higher liability for these inherited disorders. Breeding decisions based on test results or diagnoses by health conscious breeders is a powerful tool for improved genetic health.

When informing a breeder of a diagnosis of genetic disease in a dog or cat that they have bred, you may hear several responses. A positive response would include concern, but also gratitude for the information. You cannot modify breeding practices and improve health without knowledge of the good and bad traits being produced. More negative responses include: I didn't know that was a problem in my breed. I have never produced that before. I'm not really a breeder - I just bred my own dog (or cat). I don't make money selling my kittens (or puppies). Genetic tests are so expensive. I was assured that the stud was tested negative for that disease. I didn't even know there was a test for that. That's not a genetic disease: We call them runts - it just happens. I didn't know about any of this.

Excuse; noun. An explanation offered for a release from an obligation or responsibility

Occasionally a genetic disease just appears without warning. However, most common genetic diseases are predictable. Using valid breeding strategies, these genetic diseases are for the most part preventable. It is time for us as veterinarians, breeders, AND the general public to step up to our ethical obligation and responsibility regarding the prevention of genetic disease.

Responsibilities of Veterinarians

When someone calls the veterinary hospital to make an initial appointment for a kitten or puppy, the owner should be told to bring all of the paperwork provided by the breeder or pet store. This includes not only the prior medical care, but the registration paperwork that lists the sire and dam. On receiving the paperwork, the health test requirements for the breed are identified by looking up the breed. For dogs, these are listed on the Canine Health Information Center (CHIC) website: www.caninehealthinfo.org/breeds.html. A similar listing of tests is not currently available for cats, however breed related diseases are found on the Feline Advisory Bureau (FAB-UK) website: www.fabcats.org/breeders/inherited_disorders.

For many disorders, genetic test results for individual breeding animals are available on-line. The Orthopedic Foundation for Animals maintains registries for testable genetic disorders in dogs and cats on their searchable website: www.offa.org/search.html. (Figure 1) You can type in the parent's name or registration number (from any registry; AKC, CFA, TICA, UKC, Sally's Registry, etc.), and if test information is available the animal's webpage will come up. This is Facebook for cats and dogs, with their own web pages and health test information. (Figure 2) If a dog's information does not come up on the OFA website, you should also check the Canine Eye Registry Foundation (CERF) website for eye examination results: www.vmdb.org/verify.html.

Click on the chart to see a larger view.

If test results are not available on the web-based registries, ask the owner if the breeder provided them with verification of each of the required genetic test results on the parents; i.e., a copy of the official test results from the testing agencies. For testable cat diseases there is currently no web-based registry. Persian or Himalayan cats should have polycystic kidney disease (PKD) results, and Maine Coon Cats and Ragdolls should have hypertrophic cardiomyopathy (HCM) results. A list of available genotypic tests is included in the Tufts conference proceedings: www.vin.com/tufts/2009.

Click on the chart to see a larger view.

If no verified test results are available, then the puppy or kitten was not bred by a health conscious breeder. There is no expectation of genetic health in your patient, and you and the owner can only hope for good health.

When a client tells you that they are planning on breeding a dog or cat, you can look up the pre-breeding health test requirements on the CHIC or FAB websites and print these out for them. You can provide many of the tests yourself (radiographs, thyroid profile, or cheek swab or blood samples for genetic tests). For eye examinations or heart examinations by a cardiologist, you can assist your client by providing information on local health screening clinics. These can be found on the OFA website: http://www.offa.org/clinics.html, or on an excellently maintained Cavalier King Charles Spaniel website: http://www.cavalierhealth.org/health_clinics.htm. You must emphasize the ethical responsibility of pre-breeding genetic testing, or a decision to not breed their animal. Genetic testing is a requirement, not a choice.

If a client is looking to purchase a purebred or designer-bred dog or a pedigreed cat, you should counsel them on the behavioral and genetic expectations for the selected breeds. Provide them with a list of the genetic health test requirements from the CHIC or FAB websites. Ensure they understand that they should only purchase a pet from parents that have verified results of their breed-specific required health tests. See Responsibilities of the General Public (below) for more information.

Responsibilities of Breeders

It is the ethical responsibility and obligation of all breeders to perform the available required pre-breeding genetic health tests on prospective breeding stock. A breeder is anyone that plans a mating between two dogs or cats. These include matings between two members of the same breed, or crosses between two members of different breeds (designer matings). The fallacy that mixed-breed dogs and random-bred cats have less genetic disease is disproven every day in veterinary hospitals. The most common genetic diseases of; canine hip dysplasia, valvular heart disease, patella luxation, hypothyroidism, feline diabetes, and lower urinary tract disease/inflammatory cystitis occur at similar frequencies in mixed-breed versus pure-bred populations. If two animals are purposely bred, then the breed specific genetic testing for each parent is required.

Most genetic tests only need to be done once in the prospective breeding animal's lifetime. Others (eye examinations, phenotypic heart examinations, thyroid profile, etc.) should be repeated, depending on the breed specific age of onset of the disorder, and age requirement for diagnosis.

If you are not willing or able to have the prescribed pre-breeding genetic tests performed, then you should find a different hobby or profession. Dogs and cats are living beings. It is not ethical to forgo the obligation of genetic testing.

Breed specific pre-breeding health test requirements are available on the CHIC or FAB websites (see links above). It is not necessary that your breeding stock pass all of the required health tests. Dogs become CHIC certified by completing the health requirements, regardless of the test results. This shows health consciousness. With direct genetic tests for recessive disorders, carriers can be bred to normal testing mates. This prevents affected offspring from being produced. The long-term goal is to have normal testing breeding stock. With quality carrier breeding stock, you can prevent affected offspring, and replace quality carriers with normal testing offspring for your next generation of breeding stock.

Dogs or cats affected with an autosomal dominant disease should be selected against, as half of their offspring will be affected with the genetic disorder. With polygenic or complexly inherited disorders, knowledge of the test results or affected status of the close relatives allows the breeder to recognize the risk of producing the genetic disorder. Breadth of pedigree normalcy (test results of the siblings of prospective breeding animals) gives a better indication of the genetic load of normal genes that the prospective breeding animal may carry. Breadth and depth of pedigree normalcy can be visualized in vertical pedigrees on the animal's page of the OFA website (Figure 3). For more complete breeding recommendations, see Breeding Strategies for the Management of Genetic Disorders on the Tufts conference website: www.vin.com/tufts/2009.

As stated previously, complexly inherited disease and diseases without direct tests for carriers cannot absolutely be prevented. No one wants to produce genetic disease, and we can all empathize when it does occur. If you are doing genetic testing and plan matings accordingly, you are doing your best to be health conscious and fulfilling your breeder responsibility.

Everyone loves their breed, and their own breeding stock. The more genetic tests that are developed, the greater chance there is of identifying an undesirable gene in your animal. Conscientious breeders understand that negative test results limit their breeding options. With direct gene tests, you can use carriers when bred to normal testing mates. For disorders without direct gene tests, you may have to choose a normal relative, as opposed to one you were planning on using in the next generation. We all recognize the excuse of, "Don't throw the baby out with the bath water." Matings should be planned that prevent or minimize the risk of producing genetic disease.

When your prospective breeding stock has a carrier or affected test result, please release this information to the OFA or other listing registry. (You have to mail CERF results in to release negative eye examination results.) If negative test results are not made available, then other breeders will not be able to ascertain the disease risk of their own breeding stock to make informed breeding decisions. An OFA webpage of all normal individuals is great to see, but of little value if those with negative results are not listed. As opposed to the stigma that used to be attached to the appearance of genetic disease, the stigma now rests on those that hide the occurrence of genetic disease. Dealing with genetic disorders is a community effort.

When making breeding decisions, you can search the OFA, CERF, CHIC or other websites for genetic test results on prospective mates. The OFA search page is extremely flexible and useful on search requirements (Figure 1 above). If test results are not available on dogs and cats that have already been bred, then it must be assumed that they are affected or carriers - otherwise the results would be available.

When selling a puppy or kitten, please provide your new owners with full documentation of the health test results (copies of official test results) on the parents. If early direct genetic testing was done on the puppies or kittens, these results should be provided. It is not enough to say that the testing was done. If testing was done then you have the paperwork, and it should be provided. It must be impressed upon the public that health consciousness is one of the most important considerations when getting a kitten or puppy. Health guarantees that provide for replacement of puppies or kittens with genetic defects are not a replacement for health testing. Such a guarantee is of little value, as no one wants to part with their family member once the emotional bonds have been made. This is not a toaster.

You should follow up on offspring that you have produced. Have birthday parties, or call owners on the pet's birthday to see how they are doing. Owners will value your interest in their pet's well being. If an owner's pet is discovered to have a problem, show your concern. Owners understand that a breeder cannot predict or prevent every health problem, and will appreciate your health consciousness.

Responsibilities of the General Public

When you as a consumer get a puppy or a kitten, the emotional aspect of adding a new member of your family often overwhelms the rational aspect of this important decision. Acquiring a new pet should not be an impulse decision. Your new pet will hopefully be with you for the next 10 to 15 years. You should spend as much time researching this decision as you do when you purchase a new car or a refrigerator.

You need to research whether a specific breed is suitable for you and your home. You also need to research the breed specific health testing requirements for the selected breed from the CHIC or FAB websites (links above). Both parents of kittens or puppies that you are considering should have all of their breed specific test results completed and available on official on-line registries such as the OFA and CERF (links above), or you should be provided with copies of the official test results on the parents. Whether you are purchasing from a private breeder, one you found on the internet, or a pet store, the parental health testing results should be available. If they are not available, then just walk away - regardless of how cute the puppy or kitten.
Statements of testing by the breeder, or on a breeder website are not sufficient to document health test status. If the testing has been done, the breeder will be happy to provide the official documentation that they are a health conscious breeder. All genetic disease is not preventable. A breeder that has performed the required pre-breeding health tests is doing what they can to provide a healthy pet.

Health guarantees that provide replacement for pets with genetic disease do not eliminate the need for genetic testing. If a breeder states that they do not have the health test documentation, but offer a guarantee of genetic health, walk away. They have not fulfilled their ethical responsibility and obligation of health testing.

The general public is the engine that drives the pet breeding industry. If the general public demands kittens and puppies from health tested breeding stock, then the market will change to favor health conscious breeders. If people can easily sell pets to the public on a website without any health tests being done, then there is no market force to change the situation to improve the genetic health of dogs and cats. It is your choice of where you get a puppy or kitten. It is the general public's obligation to document genetic health testing from breeders.

The frequency of genetic diseases can be significantly decreased, if not eliminated by valid testing and breeding selection in purposely bred dogs and cats. We are now at the point where the tools are available, and the information is well established. It is time to put an end to the excuse of ignorance of the breeder, veterinarian, or general public in their roles and responsibilities to improve the health of dogs and cats. It is up to all of us to educate each other about producing genetically healthy cats and dogs, and call for documentation of health testing of all breeding stock.

This article may be reproduced with the permission of the author. Jerold.Bell{at}tufts.edu

PART III

Genetic Diversity

Some breed clubs advocate codes of ethics that discourage linebreeding or inbreeding, as an attempt to increase breed genetic diversity. The types of matings utilized do not cause the loss of genes from a breed gene pool.  It occurs through selection; the use and non-use of offspring. If some breeders linebreed to certain dogs that they favor, and others linebreed to other dogs that they favor, then breed-wide genetic diversity is maintained.

In a theoretical mating with four offspring, we are dealing with four gene pairs. The sire is homozygous at 50% of his gene pairs (two out of four), while the dam is homozygous at 75% of her gene pairs. It is reasonable to assume that she is more inbred than the sire.

A basic tenet of population genetics is that gene frequencies do not change from the parental generation to the offspring. This will occur regardless of the homozygosity or heterozygosity of the parents, or whether the mating is an outbreeding, linebreeding, or inbreeding. This is the nature of genetic recombination.

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There is a lack of gene diversity at the first (olive) gene pair, so that only one type of gene combination can be produced: homozygous olive. As the sire is homozygous lime at the third gene pair, and the dam is homozygous blue, all offspring will be heterozygous at the third gene pair. Depending on the dominant or recessive nature of the blue or lime genes, all offspring will appear the same for this trait due to a uniformity of heterozygosity.

If offspring D is used as a prolific breeder, and none of the other offspring are bred to a great extent, gene frequencies in the breed will change. As dog D lacks the orange gene in the second pair and the purple gene in the fourth pair, the frequencies of these genes will diminish in the breed. They will be replaced by higher frequencies of the red and pink genes. This shifts the gene pool, and the breed's genetic diversity. Of course, dogs have more than four gene pairs, and the overuse of dog D to the exception of others can affect the gene frequency of thousands of genes. Again, it is selection (for example of dog D to the exception of others), and not the types of matings he is involved in that alters gene frequencies.

Breeders should select the best individuals from all kennel lines, so as to not create new genetic bottlenecks. There is a tendency for many breeders to breed to a male; who produced no epileptics in matings to several epileptic dams, to an OFA excellent stud, or to the top winning dog in the show ring. Regardless of the popularity of the breed, if everyone is breeding to a single studdog, (the popular sire syndrome) the gene pool will drift in that dog's direction and there will be a loss of genetic diversity. Too much breeding to one dog will give the gene pool an extraordinary dose of his genes, and also whatever detrimental recessives he may carry, to be uncovered in later generations. This can cause future breed related genetic disease through the founders effect.

Dogs who are poor examples of the breed should not be used simply to maintain diversity. Related dogs with desirable qualities will maintain diversity, and improve the breed. Breeders should concentrate on selecting toward a breed standard, based on the ideal temperament, performance, and conformation, and should select against the significant breed related health issues. Using progeny and sib-based information to select against both polygenic disorders and those without a known mode of inheritance will allow greater control.

Rare breeds with small gene pools have concerns about genetic diversity. What constitutes acceptable diversity versus too restricted diversity? The problems with genetic diversity in purebred populations concern the fixing of deleterious recessive genes, which when homozygous cause impaired health. Lethal recessives place a drain on the gene pool either prenatally, or before reproductive age. They can manifest themselves through smaller litter size, or neonatal death. Other deleterious recessives cause disease, while not affecting reproduction.

Problems with a lack of genetic diversity arise at the gene locus level. There is no specific level or percentage of inbreeding that causes impaired health or vigor. It has been shown that some inbred strains of animals thrive generation after generation, while others fail to thrive. If there is no diversity (non-variable gene pairs for a breed) but the homozygote is not detrimental, there is no effect on breed health. The characteristics that make a breed reproduce true to its standard are based on non-variable gene pairs. A genetic health problem arises for a breed when a detrimental allele increases in frequency and homozygosity.

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Genetic Conservation

The perceived problem of a limited gene pool has caused some breeds to advocate outbreeding of all dogs. Studies in genetic conservation and rare breeds have shown that this practice actually contributes to the loss of genetic diversity. By uniformly crossing all "lines" in a breed, you eliminate the differences between them, and therefore the diversity between individuals. This practice in livestock breeding has significantly reduced diversity, and caused the loss of unique rare breeds. The process of maintaining healthy "lines" or families of dogs, with many breeders crossing between lines and breeding back as they see fit maintains diversity in the gene pool. It is the varied opinion of breeders as to what constitutes the ideal dog, and their selection of breeding stock that maintains breed diversity.

The Doberman Pincher breed is large, and genetically diverse. The breed has a problem with von Willibrand's disease, an autosomal recessive bleeding disorder.  Based on genetic testing, the frequency of the defective gene is 52.5% (23% normal, 49% carriers and 28% affected). Therefore, there is diminished genetic diversity in this breed at the von Willibrand's locus.  Doberman Pincher breeders can identify carrier and affected dogs, and decrease the defective gene frequency through selection of normal-testing offspring for breeding.  By not just eliminating carriers, but replacing them with normal-testing offspring, genetic diversity will be conserved.

Dalmatians have a defective autosomal recessive purine metabolism gene that can cause urate bladder stones and crystals, and/or a skin disorder called Dalmatian Bronzing Syndrome. It is believed that all Dalmatians are homozygous recessive for the defective gene. At one time, the breed and the AKC approved a crossbreeding program to a few Pointers, to bring normal-purine metabolism genes into the gene pool. The program was abandoned by the National club for several reasons including; concern about the impact of other Pointer genes foreign to the Dalmatian gene pool, and unacceptable spotting patterns in the crossbreds. The crossbreeding program still exists, and greater than ten generations from pure pointer influence is producing properly spotted, normal-purine Dalmatians. If the breed ever allows these dogs into the gene pool, they will have to be concerned about popular sire effects and limited diversity from using the normal-purine dogs too extensively.

The Akita has several breed-related autoimmune disorders that although infrequent, occur at frequencies greater than other breeds. These include uveodermatological syndrome, pemphigus, sebaceous adenitis, juvenile arthritis, myasthenia gravis, and autoimmune thyroiditis. Research has shown that there is a lack of diversity at a major histocompatability gene in the breed, with a single allele occurring at a very high frequency. The major histocompatability complex is integral to a properly functioning immune system. The relationship of this lack of diversity to autoimmunity is being studied.

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Putting It All Together

Decisions to linebreed, inbreed or outbreed should be made based on the knowledge of an individual dog's traits and those of its ancestors. Inbreeding will quickly identify the good and bad recessive genes the parents share in the offspring. Unless you have prior knowledge of what the pups of milder linebreedings on the common ancestors were like, you may be exposing your puppies (and puppy buyers) to extraordinary risk of genetic defects. In your matings, the inbreeding coefficient should only increase because you are specifically linebreeding (increasing the percentage of blood) to selected ancestors.

Don't set too many goals in each generation, or your selective pressure for each goal will necessarily become weaker. Genetically complex or dominant traits should be addressed early in a long-range breeding plan, as they may take several generations to fix. Traits with major dominant genes become fixed more slowly, as the heterozygous (Aa) individuals in a breed will not be readily differentiated from the homozygous-dominant (AA) individuals. Desirable recessive traits can be fixed in one generation because individuals that show such characteristics are homozygous for the recessive genes. Dogs that breed true for numerous matings and generations should be preferentially selected for breeding stock. This prepotency is due to homozygosity of dominant (AA) and recessive (aa) genes.

If you linebreed and are not happy with what you have produced, breeding to a less related line immediately creates an outbred line and brings in new traits. Repeated outbreeding to attempt to dilute detrimental recessive genes is not a desirable method of genetic disease control. Recessive genes cannot be diluted; they are either present or not. Outbreeding carriers multiplies and further spreads the defective gene(s) in the gene pool. If a dog is a known carrier or has high carrier risk through pedigree analysis, it can be retired from breeding, and replaced with one or two quality offspring. Those offspring should be bred, and replaced with quality offspring of their own, with the hope of losing the defective gene.

Trying to develop your breeding program scientifically can be an arduous, but rewarding, endeavor. By taking the time to understand the types of breeding schemes available, you can concentrate on your goals towards producing a better dog.

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Further Reading:

If you are interested in learning more about these subjects, consult the following books:

• Abnormalities of Companion Animals: Analysis of Heritability
  C.W. Foley, J.F. Lasley, and G.D. Osweiler, Iowa State University Press, Ames, Iowa. 1979.
• Genetics for Dog Breeders
  F.B. Hutt, W.H. Freeman Co, San Francisco, California. 1979.
• Genetics for Dog Breeders
  R. Robinson, Pergamon Press, Oxford England. 1990.
• Genetics of the Dog (equally applicable to cats & other animals)
  M.B. Willis, Howell Book House, New York, New York. 1989.
• Veterinary Genetics
  F. W. Nicholas, Clarendon Press, Oxford England. 1987.

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PART II

Pedigree Analysis

Geneticists' and breeders' definitions of inbreeding vary. A geneticist views inbreeding as a measurable number that goes up whenever there is a common ancestor between the sire's and dam's sides of the pedigree; a breeder considers inbreeding to be close inbreeding, such as father-to-daughter or brother-to-sister matings. A common ancestor, even in the eighth generation, will increase the measurable amount of inbreeding in the pedigree.

The Inbreeding Coefficient (or Wright's coefficient) is an estimate of the percentage of all the variable gene pairs that are homozygous due to inheritance from common ancestors. It is also the average chance that any single gene pair is homozygous due to inheritance from a common ancestor. In order to determine whether a particular mating is an outbreeding or inbreeding relative to your breed, you must determine the breed's average inbreeding coefficient. The average inbreeding coefficient of a breed will vary depending on the breed's popularity or the age of its breeding population. A mating with an inbreeding coefficient of 14 percent based on a ten generation pedigree, would be considered moderate inbreeding for a Labrador Retriever (a popular breed with a low average inbreeding coefficient), but would be considered outbred for an Irish Water Spaniel (a rare breed with a higher average inbreeding coefficient).

For the calculated inbreeding coefficient of a pedigree to be accurate, it must be based on several generations. Inbreeding in the fifth and later generations (background inbreeding) often has a profound effect on the genetic makeup of the offspring represented by the pedigree. In studies conducted on dog breeds, the difference in inbreeding coefficients based on four versus eight generation pedigrees varied immensely. A four generation pedigree containing 28 unique ancestors for 30 positions in the pedigree could generate a low inbreeding coefficient, while eight generations of the same pedigree, which contained 212 unique ancestors out of 510 possible positions, had a considerably higher inbreeding coefficient. What seemed like an outbred mix of genes in a couple of generations, appeared as a linebred concentration of genes from influential ancestors in extended generations.

The process of calculating coefficients is too complex to present here. Several books that include how to compute coefficients are indicated at the end of this article; some computerized canine pedigree programs also compute coefficients. The analyses in this article were performed using CompuPed, by RCI Software.

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Pedigree of Gordon Setter: "Laurel Hill Braxfield Bilye"

(a spayed female owned by Dr. Jerold and Mrs. Candice Bell, and co-bred by Mary Poos and Laura Bedford.)