World of Cats & Dogs

Autosomal Recessive Disorders

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 normals to normals, or carriers to normal-testing individuals. This prevents affected offspring from being produced.

Breeders are the custodians of their breed’s past and future. “Above all, do no harm” is a primary oath of all medical professionals. Genetic tests are powerful tools, and their use can cause significant positive or negative changes to breed gene pools. Once a genetic test is developed that allows breeders to determine if an animal is a carrier of a defective gene, many owners are likely to simply eliminate carriers from breeding. Although doing so is human nature, this temptation must be overcome. If an owner would breed an individual if it tested normal for a genetic disease, then a carrier result should not change that decision. A direct genetic test should not alter WHO gets bred, only WHO THEY GET BRED TO. One defective gene that can be identified through a genetic test out of tens of thousands of genes is not a reason to stop breeding. A genetic test that should be used to help maintain breed quality and diversity should not result in limiting it.

We know that most individuals carry some unfavorable recessive genes. The more genetic tests that are developed, the greater chance there is of identifying an undesirable gene in a breeding animal. History has shown that breeders can be successful in reducing breed-wide genetic disease through testing and making informed breeding choices. However, there are also examples of breeds that have actually experienced more problems as a result of unwarranted culling and restriction of their gene pools. These problems include: 1) Reducing the incidence of one disease and increasing the incidence of another by repeated use of males known to be clear of the gene that causes the first condition. 2) Creating bottlenecks and diminishing diversity by eliminating all carriers of a gene from the breeding pool, instead of breeding and replacing them. 3) Concentrating on the presence or absence of a single gene and not the quality of the whole animal.

The aim is to replace the carrier breeding-animal with a normal-testing offspring that equals or exceeds it in quality. Additional carrier testing offspring should not be placed in breeding homes; as the goal is to reduce the frequency of the defective gene in the population. As each breeder tests and replaces carrier animals with normal-testing offspring, the problem for the breed as a whole diminishes, while not restricting gene pool diversity.

The problem with a simple autosomal recessive disorder for which no carrier test exists is the propagation and dissemination of unapparent carriers in the gene pool. A quality individual that is found to be a carrier of a recessive gene can be retired from breeding and replaced with a quality relative or prior-born offspring. The genes of the retired individual can thus be preserved through the selected relative, but the carrier risk can be cut in half. 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 representative offspring. The rest of the litter should be placed in non-breeding (pet) homes. With this mating scheme, you are 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.

Breeders must assess the carrier risk of each individual animal in their breeding program. An open health registry that is supported by the parent club makes it easier for breeders to objectively assess these matters. An example is the genetic disease control program for cerebellar abiotrophy by the Scottish Terrier Club of America (www.stca.biz/health-registries/ca-registry). By determining the average carrier-risk for the breeding population, breeders can select matings that have a projected risk that is lower than the breed average. Relative risk assessments only take into account the identified carrier and affected individuals in the pedigree. Therefore, these estimates determine the minimum risk based on the information available. If additional affected relatives to the pedigree are diagnosed, the computed risk will rise. The relative risk pedigree calculator on the Scottish Terrier website can be used for any breed to compute carrier and affected risk for any simple autosomal recessive disorder.

If a quality breeding animal is at high risk of being a carrier, the best advice is to breed to an individual that has a low risk. Using relative-risk assessment as a tool, breeders should replace higher-risk breeding animals with lower-risk offspring that are equal to or better than their parents in quality. A negative aspect of pedigree analysis is that it selects against families, regardless of an individual’s normal or carrier status. On the other hand, it allows for the objective risk assessment and continuation of lines that might otherwise be abandoned due to high carrier-risk.