Jerold S. Bell, DVM
Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton, MA, USA
Genetic tests are power tools, whose use can have a significant positive or negative impact on a breed's gene pool. As with all power tools, they should come with an instruction manual on safety and their proper use.
The quantity and commercial availability of genetic tests offered for making breeding decisions are rapidly increasing. Breeders must understand the types of genetic tests that are available (phenotypic diagnostic tests, direct mutation DNA tests, linked marker-based DNA tests, susceptibility allele tests for complexly inherited disorders, pedigree and molecular genetic coefficients, EBVs and GBVs, etc.), and specifically what these tests tell them about the cats and dogs being tested. Along with the types of tests available, breeders must understand their proper use. Many of these issues are discussed in the article, "Maneuvering the Maze of Genetic Test: Interpretation and Utilization."
The fact that a genetic test exists does not automatically qualify it for global utilization. With the plethora of genetic tests and their commercialization comes a realization that breeds can be tested into oblivion with selection that often has no bearing on health or quality. There are historical records of how improper use of genetic tests have reduced breed genetic diversity as well as increased the frequency of other deleterious genes.
Selection is what created breeds, and selection is what will maintain breeds and improve their genetic health. Selection should be directed toward specific goals that directly improve the breed. Positive selection toward breed standards should ensure that they are not linked to disease liability. These may be conformational, behavioral, and/or working standards. Selection against disease liability should have a goal of preventing genetic disease without significantly eliminating breeding lines or restricting breed genetic diversity.
Genetic tests, pedigree and molecular genetic coefficients, and mating practices are tools that can allow the breeder to achieve defined breeding goals. When breeders begin to use these tools as the goals themselves, positive selective pressure is reduced, and breed gene pools will drift. Breeders must not lose sight of the fact that they are breeding entire individuals and not a heart, an eye, a hip, or a coefficient number.
When evaluating an individual for breeding, the breeder must objectively assess the positive and negative traits and disorders displayed. Knowledge of the common hereditary disorders in the breed is important, as is their available genetic screening tests. For most dog breeds, these are listed in their breed page on the Canine Health Information Center website (www.caninehealthinfo.org/breeds.html). (VIN editor: This link was modified as of 9-10-13.) A similar website for cat breeds does not exist; however, the Feline Advisory Bureau has a website detailing genetic disorders of cat breeds (www.fabcats.org/breeders/inherited_disorders).
Traits requiring selection in a mating should be listed and prioritized. Disorders that cause morbidity or mortality should have a high priority in selection. Traits and disorders caused by simple Mendelian genes can be changed and eliminated in a single generation. However, breeders should recognize that undesirable genes can be eliminated without eliminating breeding lines and affecting breed genetic diversity.
With testable simple Mendelian recessive genes causing genetic disorders, quality carriers can be bred to normal-testing mates and never produce the disorder. Quality normal-testing offspring should replace the carrier parent for breeding in the next generation to continue the breeding line. In this way, you lose the single testable gene but continue the breeding line. Genetic tests should increase the options for breeding and not limit them.
The typical response of a breeder on being informed of a carrier genetic test result is to remove the prospective breeding individual from a breeding program. If a majority of breeders do this, it can significantly limit the gene pool diversity of the breed. 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 for a simple recessive trait does not alter who gets bred, only who they get bred to (Henthorn P, personal communication).
Aside from preventing the production of affected individuals, breeders should select against placing new carrier-testing offspring into breeding homes. Carrier to normal matings produce, on average, 50% carriers and 50% normal-testing offspring - a much higher carrier frequency than most breed-related disease liability genes. It is important to progressively decrease the frequency of deleterious genes in a breed, to increase breeding choices. This becomes especially important when there are several testable genes in a breed. With high carrier frequencies, selection can become more of an effort to prevent disease than to create the most desirable breed representative.
Complexly inherited traits will usually require more than one generation of selection to alter the genetic load of liability genes. Genetic selection should rely on genetic tests or phenotypic evaluations that are reflective and associated with causative genes. With complexly inherited traits (and with simple recessive traits that have no test for carriers), the phenotype of first-degree relatives (siblings, parents, and siblings of parents) best represent the range of liability genes that may be carried by the prospective breeding individual. This "breadth of pedigree" analysis can be evaluated through estimated breeding values (EBVs), or vertical pedigrees on the OFA website (www.offa.org).
Prospective mates should be listed and rated for the traits and disorders, in order to see which individuals might provide the greatest selective pressure for the most important traits. If an individual is highly desirable due to its traits and ability to pass them on, but also has several deleterious genes identified through genetic testing, then a parent, sibling, or prior-born offspring may provide the desired combination of traits and genetic test results.
Once a breeder has prioritized the traits and disorders that could undergo selection, (s)he must decide which will undergo selection in the next mating. The more traits that are undergoing selection, the less selective pressure that can be applied to any single trait.
As selection pressure is diminished by selection for test results that do not affect individual health and fitness, these should be avoided. Some commercial companies counsel to use genetic tests or coefficients as breeding goals. These include manipulation of MHC (major histocompatibility complex) haplotypes, or whole-breed outbreeding recommendations.
Certain specific MHC haplotypes are found to be linked to susceptibility for specific genetic disorders. However, general individual homozygosity or breed haplotype frequencies of the MHC loci by themselves have not been linked to disease or impaired health. In a study of semi-feral village dogs from around the world, it was found that 1) they share many of the same MHC haplotypes with purebred dogs; 2) they have many unique haplotypes that are not found in purebred dogs; and 3) purebred dogs also have many unique haplotypes that are not shared with village dogs. Purebred dogs do show increased homozygosity of MHC loci consistent with their large haplotype blocks and long linkage disequilibrium; however, their predicted genetic depletion versus village dogs was not found (Kennedy LJ, et al. Do village dogs retain more major histocompatibility complex diversity compared to pedigree breed dogs? Poster presentation at the 7th International Conference on Advances in Canine and Feline Genomics and Inherited Disease; Cambridge, MA).
There is a movement to recommend generalized outbreeding programs for breeds to ostensibly retain genetic diversity. However, the types of matings used (linebreeding versus outbreeding) do not change gene frequencies. It is the selection of breeding animals that alters gene frequencies. The lecture notes, "Inbreeding, Outbreeding and Breed Evolution," in the 6th Tufts Canine & Feline Breeding and Genetics Conference proceedings provide further depth to this issue.
Breeders must be wary of commercial offerings of genetic tests for genes that have not been proven to cause disease in their breed. This includes testing panels of collections of identified disease liability genes. Just because a gene is linked to disease in one breed does not automatically mean that it is linked to disease in all breeds. Causality or liability must be validated in each breed. If causality cannot be documented, then unwarranted selection just puts unnecessary pressure on the breed gene pool and reduces the selective pressure on traits that are actually important to the breed.
Selection should be directed for specific desirable traits and against disease liability genes. Efforts should be made to avoid the loss of quality breeding lines and genetic diversity in mating decisions. The most important aspect of maintaining breed genetic diversity is avoidance of the popular sire syndrome. Expanding or large, stable breeding populations are the best buffer against gene loss. Genetic tests provide excellent tools for breed improvement, and their proper utilization will allow breeders to see continued improvement in health and quality.