Understanding How the Genetics of Purebreds and Mixed-Breeds Affect Genetic Counseling in Practice
Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA
Genetic counseling for the individual patient is similar regardless of their purebred or mixed-breed ancestry. Common genetic disorders are caused by ancient disease liability mutations that preceded breed formation. They present at similar frequencies in purebred and mixed-breed cats and dogs. These disorders include the following: allergies, diabetes, heart disease, feline bladder disease, hereditary cancer, musculoskeletal disease, cataracts, and cruciate ligament disease.
Hereditary disease tends to present as chronic or recurrent episodic disease. Counseling to mitigate the clinical effects of hereditary disease is performed daily by veterinarians in practice. This includes diet modification in many diseases (diabetes, food allergy, urolithiasis, FLUTD, PSS, etc.), avoidance and prevention of allergic reactivity, behavioral counseling, modification of weight and activity, and other medical and surgical management. Breeding management to prevent the production of offspring with hereditary disease varies based on the purebred or random-bred background of the parents. Understanding the genetic architecture of purebred versus mixed-breed dogs and cats allows a better appreciation of appropriate genetic counseling recommendations.
All dog and cat breeds originate from a small population of either related individuals or individuals who share a common conformational, behavioral, or working phenotype. Through selection, a breed standard is developed. Individual cats and dogs that do not adhere to the standard or who demonstrate deleterious traits or disorders are purged from breeding. Those individuals who demonstrate and propagate desirable characteristics will have an increasing influence on the gene pool through multiple generations of descendants. Once breed characteristics are fixed in the population, it can go through an expansion stage where the population grows.
Pedigree of a typical purebred dog or cat (individual at the left). Breed founders appear at the right. Each breed goes through a purging stage, and then expansion stage.
All breeds will have several influential ancestors that appear far back in pedigrees but pass on a high percentage of their genes to every individual in the breed. For example, all Burmese cats share on average 22.9% of genes with founder Wong Mau (close to the contribution of a grandparent), and 77.9% of his genes have been retained in the breed population. He does not appear on average until the 19th generation but appears over 1.5 billion times in every Burmese pedigree. Bailie of Bothkennar was born in the 1940s and contributes 32.6% of his genes to every modern bearded collie. This process of breed evolution causes a loss of genetic diversity through the purging of undesirable individuals and the concentration and homozygosity of genes of high-quality influential ancestors. This is an expected consequence of breed evolution and is not detrimental to the breed.
Deleterious genes can originate from a random mutation and be propagated through breed ancestors. Conversely, genes causing genetic disorders can be linked to a selected trait on a shared chromosome (e.g., hyperuricosuria and dalmatian spotting), or genetic disorders can be caused by direct selection for disease-causing phenotypic traits (e.g., feline and canine brachycephalic syndrome). The specific genes causing many common breed-specific genetic disorders have already been dispersed in breed gene pools. Therefore, the chance of breeding two carriers together is based on the frequency of the deleterious gene(s) in the population, and not necessarily the type (outbreeding or linebreeding) of mating. In order to have selective pressure for positive traits and against negative traits or disorders, there must be variation and genetic differences between individuals in the gene pool. This requires distinct family lines. Pure breeds evolved in a different era when dedicated breeders judiciously selected against individuals that were unhealthy, could not thrive, could not excel at working tasks (for working dog breeds), or did not conform to a healthy breed “standard.” These early breeders purged unhealthy animals and their genes from the breed gene pools. Somewhere along the way, the responsibility to select for health and produce healthy offspring disappeared from dog and cat breeding. People just breed and expect healthy offspring. People decide which cats and dogs get bred, and which get bred to each other. This is the difference between natural selection and artificial selection. If artificial selection does not select for health, then there can be no expectation of genetic health. If artificial selection selects for breed characteristics that impair health, then breed-related disease is the natural outcome. Breeding is all about selection.
Mixed-breed dogs and cats usually mate randomly and whelp without human intervention. Therefore, there is some natural selection involved if an individual fails to thrive. With the advent of mixed-breed DNA testing we are able to understand that some individuals go back to recent purebreds. However, in many instances mixed-breed individuals have chromosomal DNA segments identifying ancestral relationships to many different breeds—or to predecessors of breed founders. The occurrence of common genetic diseases in mixed-breed individuals occurs randomly due to dispersed ancient liability genes. Uncommon and breed-specific recessive or complexly inherited disease is far less likely in mixed-breed individuals. If an individual inherits a disease liability gene for such complexly inherited diseases, it is less likely that the individual will inherit the other breed-specific liability genes necessary for clinical disease.
Conservation geneticists versed in rare and endangered species have designed species survival plans (SSPs) that call for outbreeding; mating together animals that are least related to each other. The purpose of SSPs is to increase heterozygosity and randomize genes in the population to prevent the homozygous expression of deleterious recessive genes. However, natural species and artificially selected breeds have completely different, and in many instances completely opposite selection pressures and desired outcomes. SSPs call for using all available individuals in breeding and only outbreeding.
Cat and dog breeding call for selection, which requires differences between prospective mates and therefore genetic diversity between individuals. Outbreeding homogenizes the population by removing the genetic difference between individuals in the breed and making everyone “alike.” If two unrelated parents are bred together, the offspring make the two lines related. If an offspring is then outbred to a further unrelated line, their offspring make all of the lines related. Outbreeding is a self-limiting process as there will eventually be no unrelated individuals. Thus, the basic conceptual point is, “What constitutes genetic diversity? Is it the diversity within each individual (heterozygosity through outbreeding)? Or is it the diversity between each individual (maintaining diverse family lines)? These two concepts are diametrically opposed to each other and are the basic difference between random and purebred breeding. The only way to select against specific genetic disorders is to specifically select against the causative or liability genes through direct genetic testing or phenotypic genetic screening.
Counseling for Health-Conscious Breeding
In the planning of any proposed canine or feline mating, the selection of healthy parents is paramount to the health of the offspring. A pre-breeding health examination includes phenotypic examination of the major organ systems for; musculoskeletal, cardiac, ophthalmologic, gastrointestinal, pulmonary, dermatologic and behavioral abnormalities. Medical history should be examined for episodic inherited disease that cannot be identified on examination (i.e., allergies, seizures, bloat, inflammatory cystitis, urolithiasis, etc.). Individuals demonstrating hereditary disease should be selected against for breeding.
Pure breeds can also have breed-specific genetic disease due to more recent mutations. For many of these there are genetic tests that can identify causative or disease liability genes. Many breed, kennel, and cat clubs list breed-specific, pre-breeding genetic screening and testing requirements or recommendations. The advent of multiplex genetic panel testing (Canine and Feline Wisdom Health, Embark, etc.) provides genetic test results for over 180 canine and 60 feline traits and disorders. Unfortunately, most of the disease liability genes tested for in these panels are breed specific. Unless the gene(s) have been validated to cause clinical disease in other breeds or mixed breeds, the test result may not have any significance in your patient. In addition, the panel tests utilize SNPs (single nucleotide changes) instead of testing for a mutation; so false positives and negatives can occur. Breeding decisions regarding breed-validated liability genes should be based on direct mutation testing.
Typical genetic counseling recommendations utilize the breeding of carriers to non-carrier individuals and replacing the carrier parent with a quality non-carrier offspring. In this way breeding lines (and breed genetic diversity) are not abandoned and testable disease liability genes can be lost in one generation. A more in-depth discussion of genetic counseling can be found in the 2017 WSAVA Congress proceedings, “Genetic Counseling by Practicing Veterinarians”.
The public embrace of “adopt, don’t shop” and cat and dog rescue has created a demand for mixed-breed and random-bred dogs and cats that exceeds their availability. This has created the “bred-for-rescue” industry that utilizes the same breeding and transportation networks that previously supplied pet stores. The bottom line is that if any purebred or mixed-breed mating is being planned, health conscious breeding through pre-breeding health examination, genetic screening and genetic testing should be performed. This is the only way to improve the genetic health of all cats and dogs. All dogs and cats deserve to live healthy lives.