Pedigree Analysis - Part 3 - Alaskan Malamute Health

The Ins and Outs of Pedigree Analysis, Genetic
Diversity, and Genetic Disease Control

by: Jerold S. Bell, DVM

PART III

Anchor Jump Menu:
Genetic Diversity	Genetic Conservation		Putting It All Together	Further Reading

Genetic Diversity

Some breed clubs advocate codes of ethics that discourage linebreeding or inbreeding, as an attempt to increase breed genetic diversity. The types of matings utilized do not cause the loss of genes from a breed gene pool. It occurs through selection; the use and non-use of offspring. If some breeders linebreed to certain dogs that they favor, and others linebreed to other dogs that they favor, then breed-wide genetic diversity is maintained.

In a theoretical mating with four offspring, we are dealing with four gene pairs. The sire is homozygous at 50% of his gene pairs (two out of four), while the dam is homozygous at 75% of her gene pairs. It is reasonable to assume that she is more inbred than the sire.

A basic tenet of population genetics is that gene frequencies do not change from the parental generation to the offspring. This will occur regardless of the homozygosity or heterozygosity of the parents, or whether the mating is an outbreeding, linebreeding, or inbreeding. This is the nature of genetic recombination.

There is a lack of gene diversity at the first (olive) gene pair, so that only one type of gene combination can be produced: homozygous olive. As the sire is homozygous lime at the third gene pair, and the dam is homozygous blue, all offspring will be heterozygous at the third gene pair. Depending on the dominant or recessive nature of the blue or lime genes, all offspring will appear the same for this trait due to a uniformity of heterozygosity.

If offspring D is used as a prolific breeder, and none of the other offspring are bred to a great extent, gene frequencies in the breed will change. As dog D lacks the orange gene in the second pair and the purple gene in the fourth pair, the frequencies of these genes will diminish in the breed. They will be replaced by higher frequencies of the red and pink genes. This shifts the gene pool, and the breed's genetic diversity. Of course, dogs have more than four gene pairs, and the overuse of dog D to the exception of others can affect the gene frequency of thousands of genes. Again, it is selection (for example of dog D to the exception of others), and not the types of matings he is involved in that alters gene frequencies.

Breeders should select the best individuals from all kennel lines, so as to not create new genetic bottlenecks. There is a tendency for many breeders to breed to a male; who produced no epileptics in matings to several epileptic dams, to an OFA excellent stud, or to the top winning dog in the show ring. Regardless of the popularity of the breed, if everyone is breeding to a single studdog, (the popular sire syndrome) the gene pool will drift in that dog's direction and there will be a loss of genetic diversity. Too much breeding to one dog will give the gene pool an extraordinary dose of his genes, and also whatever detrimental recessives he may carry, to be uncovered in later generations. This can cause future breed related genetic disease through the founders effect.

Dogs who are poor examples of the breed should not be used simply to maintain diversity. Related dogs with desirable qualities will maintain diversity, and improve the breed. Breeders should concentrate on selecting toward a breed standard, based on the ideal temperament, performance, and conformation, and should select against the significant breed related health issues. Using progeny and sib-based information to select against both polygenic disorders and those without a known mode of inheritance will allow greater control.

Rare breeds with small gene pools have concerns about genetic diversity. What constitutes acceptable diversity versus too restricted diversity? The problems with genetic diversity in purebred populations concern the fixing of deleterious recessive genes, which when homozygous cause impaired health. Lethal recessives place a drain on the gene pool either prenatally, or before reproductive age. They can manifest themselves through smaller litter size, or neonatal death. Other deleterious recessives cause disease, while not affecting reproduction.

Problems with a lack of genetic diversity arise at the gene locus level. There is no specific level or percentage of inbreeding that causes impaired health or vigor. It has been shown that some inbred strains of animals thrive generation after generation, while others fail to thrive. If there is no diversity (non-variable gene pairs for a breed) but the homozygote is not detrimental, there is no effect on breed health. The characteristics that make a breed reproduce true to its standard are based on non-variable gene pairs. A genetic health problem arises for a breed when a detrimental allele increases in frequency and homozygosity.

Genetic Conservation

The perceived problem of a limited gene pool has caused some breeds to advocate outbreeding of all dogs. Studies in genetic conservation and rare breeds have shown that this practice actually contributes to the loss of genetic diversity. By uniformly crossing all "lines" in a breed, you eliminate the differences between them, and therefore the diversity between individuals. This practice in livestock breeding has significantly reduced diversity, and caused the loss of unique rare breeds. The process of maintaining healthy "lines" or families of dogs, with many breeders crossing between lines and breeding back as they see fit maintains diversity in the gene pool. It is the varied opinion of breeders as to what constitutes the ideal dog, and their selection of breeding stock that maintains breed diversity.

The Doberman Pincher breed is large, and genetically diverse. The breed has a problem with von Willibrand's disease, an autosomal recessive bleeding disorder. Based on genetic testing, the frequency of the defective gene is 52.5% (23% normal, 49% carriers and 28% affected). Therefore, there is diminished genetic diversity in this breed at the von Willibrand's locus. Doberman Pincher breeders can identify carrier and affected dogs, and decrease the defective gene frequency through selection of normal-testing offspring for breeding. By not just eliminating carriers, but replacing them with normal-testing offspring, genetic diversity will be conserved.

Dalmatians have a defective autosomal recessive purine metabolism gene that can cause urate bladder stones and crystals, and/or a skin disorder called Dalmatian Bronzing Syndrome. It is believed that all Dalmatians are homozygous recessive for the defective gene. At one time, the breed and the AKC approved a crossbreeding program to a few Pointers, to bring normal-purine metabolism genes into the gene pool. The program was abandoned by the National club for several reasons including; concern about the impact of other Pointer genes foreign to the Dalmatian gene pool, and unacceptable spotting patterns in the crossbreds. The crossbreeding program still exists, and greater than ten generations from pure pointer influence is producing properly spotted, normal-purine Dalmatians. If the breed ever allows these dogs into the gene pool, they will have to be concerned about popular sire effects and limited diversity from using the normal-purine dogs too extensively.

The Akita has several breed-related autoimmune disorders that although infrequent, occur at frequencies greater than other breeds. These include uveodermatological syndrome, pemphigus, sebaceous adenitis, juvenile arthritis, myasthenia gravis, and autoimmune thyroiditis. Research has shown that there is a lack of diversity at a major histocompatability gene in the breed, with a single allele occurring at a very high frequency. The major histocompatability complex is integral to a properly functioning immune system. The relationship of this lack of diversity to autoimmunity is being studied.

Putting It All Together

Decisions to linebreed, inbreed or outbreed should be made based on the knowledge of an individual dog's traits and those of its ancestors. Inbreeding will quickly identify the good and bad recessive genes the parents share in the offspring. Unless you have prior knowledge of what the pups of milder linebreedings on the common ancestors were like, you may be exposing your puppies (and puppy buyers) to extraordinary risk of genetic defects. In your matings, the inbreeding coefficient should only increase because you are specifically linebreeding (increasing the percentage of blood) to selected ancestors.

Don't set too many goals in each generation, or your selective pressure for each goal will necessarily become weaker. Genetically complex or dominant traits should be addressed early in a long-range breeding plan, as they may take several generations to fix. Traits with major dominant genes become fixed more slowly, as the heterozygous (Aa) individuals in a breed will not be readily differentiated from the homozygous-dominant (AA) individuals. Desirable recessive traits can be fixed in one generation because individuals that show such characteristics are homozygous for the recessive genes. Dogs that breed true for numerous matings and generations should be preferentially selected for breeding stock. This prepotency is due to homozygosity of dominant (AA) and recessive (aa) genes.

If you linebreed and are not happy with what you have produced, breeding to a less related line immediately creates an outbred line and brings in new traits. Repeated outbreeding to attempt to dilute detrimental recessive genes is not a desirable method of genetic disease control. Recessive genes cannot be diluted; they are either present or not. Outbreeding carriers multiplies and further spreads the defective gene(s) in the gene pool. If a dog is a known carrier or has high carrier risk through pedigree analysis, it can be retired from breeding, and replaced with one or two quality offspring. Those offspring should be bred, and replaced with quality offspring of their own, with the hope of losing the defective gene.

Trying to develop your breeding program scientifically can be an arduous, but rewarding, endeavor. By taking the time to understand the types of breeding schemes available, you can concentrate on your goals towards producing a better dog.