worse than having no test at all.
The expression of some genetic disorders cannot be altered. If a genetic test is available, it should be utilized prepurchase so that owners are not burdened with predictable genetic disease. However, for owned animals, it is a personal decision whether the owner wants to know if their pet is likely to develop a nontreatable genetic condition later in life. These include polycystic kidney disease (PKD) in Persian, Himalayan and related cats, lysosomal storage diseases, and the (poorly penetrant) liability gene for DM in susceptible breeds. These genetic tests can also assist with ruling out diagnoses in clinical patients with suspected genetic disease.
Dietary recommendations should be offered for identified genetic predispositions such as feline lower urinary tract disease in cats, dogs and cats with nonstruvite bladder stones or “crystals,” and obese “prediabetic” cats. Behavioral counseling and early training recommendations should be offered for breeds or individuals demonstrating aberrant or pathological behaviors.
Owners may also bring results of direct‐to‐consumer genetic tests or tests of ancestral breed background for interpretation (see 3.6 Genetic Testing).
3.8.5 Breeding Recommendations
As stated above, prebreeding health evaluations should be performed on all prospective breeding cats or dogs, whether for purebred or mixed‐breed planned matings. Breed‐specific genetic screening requirements should be performed, as well as a medical history review and thorough examination for hereditary disease. Dogs and cats affected with genetic disease where no genetic tests for liability genes occur should be selected against for breeding.
As stated above, the results of individual DNA tests should be evaluated to ensure that the genetic disease exists as a clinical entity in the breed and that the genetic test has been validated in the country's breed population. Some genetic tests were developed in one country but the DNA variation is not associated with the disease in all breed populations around the world. Genetic counseling and breeding decisions based on genetic test results need to be validated in each breed population.
Based on different modes of inheritance, there are guidelines to preserve breeding lines and genetic diversity while reducing the risk of producing carrier or affected individuals.
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 clear to clear or, if necessary to preserve genetic diversity, clear to quality carrier. This prevents affected offspring from being produced. Breeders should be counseled to replace carriers in a breeding program with a quality normal‐testing offspring once it is possible to do so. This will maintain breed quality and diversity. Other offspring determined to be carriers should be placed in nonbreeding pet homes. The breed frequency of disease‐causing genes is usually less than the 50% produced from normal to carrier matings. It is desirable not to increase the frequency of carriers in the population.
If a breeder finds that a quality individual is a carrier, many are inclined to remove it from their breeding consideration. This is the wrong decision for the breeder and the breed. The individual dog or cat was already determined to have qualities acceptable for breeding. Genetic testing should be used to increase a breeder's choices, not limit them. Eliminating all carriers of testable disease‐causing genes significantly restricts breed genetic diversity. Any quality individual that would have been bred if it had tested normal should still be bred if it tests as a carrier, at least until enough quality clear individuals are available for the breeding program. A genetic test for a simple autosomal recessive disorder should not change who gets bred, only who they get bred to. As each breeder tests and replaces carriers with normal‐testing offspring, the problem for the breed as a whole diminishes.
A simple autosomal recessive disorder for which no carrier test exists allows the propagation and dissemination of inapparent carriers in the gene pool. Carrier risk must be determined based on the knowledge of affected or carrier relatives. These can be visualized through vertical pedigrees on the OFA website, or other health databases (see 3.7 Genetic Health Registries and Research Organizations). Quality carriers should be replaced with nonaffected relatives and bred to individuals with low carrier risk. This can be assessed through examination of parents and grandparents (depth of pedigree normalcy), siblings and siblings to the parents (breadth of pedigree normalcy). High carrier‐risk individuals should only be bred to low‐risk individuals. The high‐risk parent should be replaced for breeding with a lower risk quality offspring. To further limit the spread of the defective gene, the offspring should be used in only a limited number of carefully planned matings, and then should also be replaced with one or two quality offspring. The rest of the litter should be placed in nonbreeding (pet) homes. With this mating scheme, the breeder is 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.
Autosomal dominant genetic disorders are usually easy to manage. As affected individuals produce approximately 50% affected offspring, they should be replaced for breeding with normal relatives. Issues with some autosomal dominant disorders include incomplete penetrance. With these disorders, the presence of the defective gene still confers risk of producing affected offspring and should be selected against.
For sex‐linked (also known as X‐linked) recessive defective genes, selecting a normal male for breeding loses the defective gene in one generation. High carrier‐risk females should not be used, as carrier females produce 50% affected sons. Rare sex‐linked dominant disorders are managed the same way as autosomal dominant disorders.
Most complex/polygenic disorders and those with an undetermined mode of inheritance have no tests for carriers, but they do have phenotypic tests that can identify affected individuals. Controlling complexly inherited disorders involves (i) identifying traits for selection that more closely represent the expression of disease‐causing genes, (ii) the standardization of nuisance factors (such as environment) that can limit selective pressure against the genes, and (iii) selecting for breadth as well as depth of pedigree normalcy as demonstrated by vertical pedigrees.
With polygenic disorders, a number of liability genes must combine to cross a threshold and produce an affected individual. A clinically normal individual from a litter that had one or no individuals affected with a complexly inherited disorder is expected to carry a lower amount of liability genes than an individual with a greater number of affected littermates. This is why it is important to screen both pet and breeding dogs and cats for complexly inherited disorders. Information on the siblings of the parents of potential breeding individuals provides additional data on which to base breeding decisions. The patient's own results represent its phenotype, but the relative's results are more representative of the patient's genotype.
If an individual is diagnosed with a genetic disorder, it can be replaced with a normal sibling or parent and bred to a mate whose risk of having liability genes is low. Replace the higher‐risk parent with a lower‐risk offspring that equals or exceeds it in other aspects, and repeat the process.
Genetic testing companies are increasingly providing genetic diversity measurements to breeders for individual dogs or cats and their proposed matings. As discussed in the chapter on genetic testing (see 3.6), all breeds by definition have high homozygosity which allows them to breed true. Homozygosity does not cause genetic disease. It is the presence of disease‐causing mutations that cause disease, and genetic counseling recommendations should be specifically directed against specific diseases. Genetic diversity has to do with maintaining unique breeding lines in a breed. It is the genetic differences between individuals in a breed that provide breed genetic diversity, not within‐individual homozygosity. It is only in rare
