Genetic Gamble - courtesy of Purina, Boxer Underground and Today's Breeder

The Genetic Gamble

"Defective genes were not created by breeders. They are due to mutations, bottlenecking and founders effects in the development of breeds." Jerold Bell, D.V.M., Canine Genetic Counsellor, Enfield, Conn.

When a breeder learns a top brood bitch is a carrier of a genetic disease, it can be devastating to a breeding program. The breeder’s first thought might be to stop breeding the bitch -- and sacrifice a superior bloodline -- for fear of producing offspring carriers.

A canine genetic counsellor might advise otherwise. Genetic counsellors advocate using sound genetic principles in assessing breeding risks. If a bitch is a carrier of a recessive genetic disorder, a breeder has options that can reduce the propagation of the defective gene, and eliminate the loss of desirable traits.

Advances in canine genetic research have resulted in more diagnostic tests to help breeders identify carriers of genetic disease and determine safe breeding practices. Breakthroughs are possible because breeders and owners of purebred dogs spend millions annually to diagnose and correct genetic disease in their breeds.

Many breed clubs have become active educators about genetic disease. Cathy Lewis of Elkhorn, Wis., a member of Purina Pro Club and the English Springer Spaniel Field Trial Association, says the group includes an educational program each year at its annual meeting. Information from a 1998 program on genetics was printed in ESSFTA’s "The Springer Spotlight" newsletter and was posted on the group’s Web site at http://www.essfta.org . Links to breed-related health and genetic topics also are featured on the Web site.

Jerold Bell, D.V.M., a canine genetic counsellor and course director for clinical veterinary genetics at Tufts University School of Veterinary Medicine in North Grafton, Mass., presented the ESSFTA program on "The Proper Use of Genetic Tests in Making Breeding Decisions."

"Defective genes were not created by breeders," Bell says. "They are due to mutations, bottlenecking and founders effects in the development of breeds." A genetic bottleneck occurs when a breed is reduced to a limited number of breeding stock from which to repopulate, he says. Bottlenecking most often occurs when a breed is imported or introduced to another country and a limited genetic pool is available.

While the pedigree of the breed may remain large, the ancestral genes are limited to those carried by the imported dogs. This process also can cause a rare gene in the original population to be widely propagated in the new population, which is called the founders effect.

Founders effect also can occur through the overuse of a breeding dog in a population. Called popular sire syndrome, this effect can cause genetic drift, which is a shifting and loss of genes in the gene pool, and can propagate previously rare genes and establish breed-related genetic disorders.

Bell’s talk covered modes of inheritance and genetic diseases in English springer spaniels, such as hip dysplasia and a congenital heart defect called ventricular septal defect. He also discussed how genetic tests can help control desired traits and genetic diseases but cautioned breeders to be aware of the dynamics of the breeding population, characteristics of the genetic disease and limitations of genetic tests.

For example, a recent mutation may only affect a small portion of the breeding population, but genetic disease control may have to be more stringent to prevent the defective gene from spreading further in the breed gene pool. "If a defective gene is found to be rare in the population and restricted to a recent mutation, we need to be more severe in our breeding so we do not disperse it into the whole gene pool," Bell says.

On the other hand, if a small-population breed has a widespread defective gene, breeders must be careful to use test results so they do not automatically spay and neuter carriers and significantly restrict the diversity in an already restricted gene pool. "In these cases, we want to breed carriers with normals and gradually replace carrier breeding stock with normal-testing offspring," says Bell.

Characteristics of Genetic Disease

The character of a genetic disease includes its severity and age of onset. Diseases that cause death or significant discomfort or those that are not treatable should have a high priority in genetic disease control. Disorders with a late-age onset are more difficult to control because genetically affected dogs can be bred before becoming clinically affected.

Bell, who is frequently asked to give talks about genetics to breed clubs, says unlike many other veterinary specialties, there is no board-certification subspecialty in genetics. "A limited number of individuals have genetic counselling expertise," he says. "The idea is to counsel breeders and dog owners to decrease carrier frequency, without affecting genetic diversity."

George Padgett, D.V.M., professor of pathology at Michigan State University in East Lansing and an authority on canine genetic disease, says, "A veterinarian’s advice to a breeder who couldn’t determine the cause of an undesirable trait was, ‘Don’t worry about it, outcross, and even if it is genetic, it will go away.’"

"This advice has messed up breeds of dogs from the beginning of time," Padgett says. "Instead of controlling a trait when there are one or two dogs, or one or two families involved, we outcross the dogs and spread the trait throughout the breed."

Greg Acland, B.V. Sc., of The James A. Baker Institute for Animal Health at Cornell University in Ithaca, N.Y., a contributor to discovery of the genes causing progressive retinal atrophy and congenital stationary night blindness, says, "For a lot of disorders, until a test is developed, the best method of breeding is a scientific evaluation to prevent carrier-to-carrier matings and eliminate affected individuals."

"Breeding decisions are not black and white," Bell says. "The best plan is to stay informed about genetic disease and be a concerned breeder for the health and welfare of the breed -- for your dogs and for the dogs you pass on to other owners."

Modes of Inheritance

A dog is the product of its genotype, or genes, acting in a specific environment. Its phenotype is an expression of both the genotype and the environment. Four modes of inheritance cause most genetic defects in dogs: autosomal recessive or simple recessive; autosomal dominant; sex-linked recessive; and polygenic.

An autosomal or simple recessive trait results when a matched pair of genes is present on any of 38 pairs of autosomes. An autosome is a nonsex chromosome. Both parents of an affected puppy are carriers of the abnormal gene, but generally do not show the trait.

An autosomal dominant trait results when a trait is expressed even though the pair of genes causing the trait are not matched. Dominant traits are expressed in the heterozygous state, which means only one parent must have a defective gene for the disorder to cause the trait to occur among the offspring.

"Canine hip dysplasia is an example of a polygenic disorder. Most breeders have attempted to control hip dysplasia by selecting for pedigree depth of normal hips. With polygenic disorders, however, the breadth of the pedigree is as important an indicator as the depth of the pedigree. The phenotype of the full siblings provides a better reflection of the genes carried by the breeding individual than the phenotype of the parents. It is expected that the phenotypically normal dog with only one dysplastic littermate would carry fewer genes for dysplasia than the phenotypically normal dog whose littermates all had hip dysplasia. If a preponderance of the siblings of the parent and grandparents are phenotypically normal, there is a greater chance of producing normal offspring." Jerold Bell, D.V.M.

Sex-linked genes can be either dominant or recessive and always appear on the X-chromosome, making females carriers. The same distinctions between autosomal dominant and recessive traits also apply to sex-linked traits. For example, the dominant gene hides the recessive gene in the female since the female has two X chromosomes. In the male, with only one X chromosome, the single recessive gene that is part of that chromosome expresses itself, causing the same trait that seems to require two genes in the female.

Polygenic traits are controlled by a number of genes, each of which adds in increments to the total phenotype. These are called complex traits because multiple genes are involved. Polygenic traits also are called complex traits because environmental factors are involved.

Genetic Testing

When trying to lower the frequency of a particular mutation, Bell says, the key is to remember there are many good genes to keep, so you don’t want to immediately eradicate all carriers from the gene pool. Genetic tests present an opportunity to focus on producing quality, genetically normal dogs by replacing carriers with normal testing offspring.

There are two types of genetic tests: linkage tests and gene-specific tests or DNA diagnostic tests. Linkage tests, in which a linked marker signifies a genetic marker and a disease gene that are close together on one chromosome, are expected to become more common as the canine genome map evolves. "If linkage tests are not appropriately interpreted, the potential exists for incorrectly assessing the relative risk of carrier status," Bell says.

Problems with linkage-based tests sometimes happen during crossover of the dog’s and bitch’s chromosomes during reproduction. This trading of chromosomal DNA is why entire chromosomes are not passed from one generation to another and why there is genetic diversity. If a crossover occurs between the genetic marker and defective gene, recombination occurs, meaning the marker might suggest there is a defective gene although the defective gene may no longer be present.

Another error occurs when a linkage test for a genetic marker recognizes a false allele that is not linked to the disease gene. Two genes at the same position on matched chromosomes are called alleles. In this instance, some dogs that look affected on the test may be carriers, while others may be homozygous normal. There is no way to differentiate the true linked marker from the false allele.

Though there are fewer gene-specific or DNA diagnostic tests, they are 100 percent accurate, matching the defective gene to the exact mutation site on the chromosome. DNA tests can be taken from blood, saliva or hair samples.

"Once there is a reliable genetic test for carriers, the procedure is to test your own dogs, request test results on the dogs you are looking to breed, and to use that information in your breeding program," Bell says. "With good tests and good breeding practices, we can greatly reduce genetic diseases."

Tips for Breed Clubs On Ways to
Control Genetic Disease

Here are some tips for breed clubs on ways to educate members about genetic disease and improve their breed. These suggestions are excerpted from the book Control of Canine Genetic Disease by George A. Padgett, D.V.M., professor of pathology at Michigan State University.

Generate a list of genetic defects in the breed by surveying members and owners, and make the list available to members and breeders. Include the mode of inheritance of each trait if it is known.

Form committees to assess the impact of each breed trait.

Advocate registration of dogs and bitches affected with genetic defects and those known to carry genes for these traits in an open registry.

Advocate registration of dogs and bitches known to be free of genes for undesirable traits.

Develop a list of dogs known to be affected or that carry genes for a given trait that are available for test matings. The list should be made freely available to breeders and members.

Determine which defects should be attacked on a breed-wide basis.

Develop a brochure describing the diseases that occur in the breed, giving clinical signs, methods of diagnosis and prognosis. This brochure should be readily available to club members, breeders and owners of breed dogs.

Develop a brochure discussing various systems that can be used to control disease and how to handle carriers and potential carriers of various traits.