The Effects of Genetic Testing: Constructive or Destructive?
By Jerold S. Bell, DVM, Tufts University School of Veterinary Medicine
(This article originally appeared in the June, 2001 issue of the AKC Gazette)
Jerold.Bell@tufts.edu

Every breed has genetic disorders. Finding tests that identify carriers of the genes which cause these disorders is a goal in all breeds. Once a genetic test is found, however, it is a double-edged sword: Its use can enable breeders to improve a breed or devastate it.

Without genetic tests, the number of dogs that can be identified as carriers is low, even though many dogs may be suspected of being carriers because they have relatives that are known to be affected. Without tests, though, genetic-disease control involves breeding higher-risk dogs to lower-risk dogs.  Dog breeds have closed gene pools; in other words, the diversity of genes in a given breed is fixed. The number of dogs removed from consideration for breeding based on concerns regarding a specific genetic disease is usually low, and therefore does not greatly alter the breed’s gene pool, or diversity.

However, once a genetic test is developed that allows breeders to positively determine if a dog is a carrier of a defective gene, many owners are likely to remove carrier dogs from their breeding stock. Although doing so is human nature, this temptation must be overcome. Any quality dog that you would have bred if it had tested normal should still be bred if it tests as a carrier. 

In such circumstances, carriers should be bred to normal-testing dogs. This ensures that affected offspring will not be produced. Carrier breeding stock should be subsequently replaced with normal-testing offspring that exceeds it in quality.  If the only quality offspring is also a carrier, then use that offspring to replace your original carrier. You have improved the quality of your breeding stock, even though the defective gene remains in this generation. It is certainly true, though, that the health of the breed does depend on diminishing the carrier frequency and not increasing it. You should therefore limit the number of carrier-testing offspring that you place in breeding homes.  This does not mean, however, that you should prevent all of them from being bred. It is important to carry on lines. A test that should be used to help maintain breed diversity should not result in limiting it.

Consider All Aspects

We know that most dogs carry some unfavorable recessive genes. The more genetic tests that are developed, the greater chance there is of identifying an undesirable gene in your dog. Remember, however, that your dog is not a single gene, an eye, a hip, or a heart. Your dog carries tens of thousands of genes, and each dog is a part of the breed's gene pool. When considering a breeding, you must consider all aspects of the dog - such as health issues, conformation, temperament and performance - and weigh the pros and cons. When a good-quality dog is found to carry a testable defective gene, there is a better option than removing that dog from your breeding program. That option is to breed it, so that you can keep its good qualities in the gene pool, and then replace it in your program with a normal-testing dog.

There are breeders who contend that no more than 10 percent of carrier dogs should be removed from breeding in each generation. Otherwise, they say, the net loss to the gene pool would be too great. In fact, less than 10 percent of all dogs in a breed are ever used for breeding. Dog breeds do not propagate according to what is known as the Hardy-Weinberg equilibrium, where all members of a group reproduce and pass on their genes to the next generation. Breeders already place tremendous pressure on their gene pools through selective breeding decisions. Indeed, breeders who focus their selective pressure on the more elusive traits in their dogs, rather than on testable and predictable single-gene conditions, are right to do so.

The Dangers

It is important that breed clubs educate their owners on how genetic tests should be properly interpreted and used. History has shown that breeders can be successful in reducing breed-wide genetic disease through testing and making informed breeding choices. You should remember, however, that 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: reducing the incidence of one disease and increasing the incidence of another by repeated use of stud dogs known to be clear of the gene that causes the first condition; creating bottlenecks and diminishing diversity by eliminating all carriers of a gene from the pool, instead of breeding and replacing them; and concentrating on the presence or absence of a single gene and not the quality of the whole dog.

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. Breeders should be counseled on how to utilize test results for the best interests of the breed.

Breeding Strategies for the Management of Genetic Disorders
Jerold S Bell, DVM, Tufts University School of Veterinary Medicine, N. Grafton, MA
Jerold.Bell@tufts.edu

With each new generation of dogs, breeders ask, “How can I continue my line and improve it?” Aside from selecting for conformation, behavior and ability, breeders must consider how they are going to reduce the incidence of whichever genetic disorders are present in their breed. There are no answers that will fit every situation. There are, however, guidelines you can follow to preserve breeding lines and genetic diversity while reducing the risk of producing dogs that carry defective genes, or are affected with genetic defects.

Autosomal Recessive Disorders

In the case of a simple autosomal recessive disorder (in other words, a disorder caused by a single, recessive gene that is not sex-linked) for which a test for carriers is available, the recommendation is to test your breeding-quality stock, and breed carriers to normal-testing dogs. The aim is to replace the carrier breeding-animal with a normal-testing offspring that equals or exceeds it in quality. You don’t want to diminish breed diversity by eliminating quality dogs from the gene pool because they are carriers. As each breeder tests and replaces carrier dogs with normal-testing dogs, the problem for the breed as a whole diminishes. (See “The Effects of Genetic Testing: Constructive or Destructive?” in the “Healthy Dog” section of the June 2001 AKC Gazette.)

For some disorders there are tests known as linkage-based carrier tests, which can generate a small percentage of false positive and negative results. When using these tests to make breeding decisions, it’s advisable to first determine whether the results correlate with the test results and the known genotypes of relatives.

When dealing with a simple autosomal recessive disorder for which no carrier test exists, breeders must assess whether each individual dog in their breeding program is at high risk of being a carrier. This requires knowledge of the carrier or affected status of close relatives in the pedigree. An open health registry that is supported by the parent club makes it easier for breeders to objectively assess these matters. By determining the average carrier-risk for the breeding population, breeders can select matings that have a projected risk which is lower than the breed average.

If breeding a dog that is at high risk of being a carrier, the best advice is to breed to a dog that has a low risk. This will significantly diminish the likelihood that affected dogs will be produced, and can reduce by up to half the risk that there will be carriers among the offspring. Using relative-risk assessment as a tool, breeders should replace higher-risk breeding dogs with lower-risk offspring that are equal to or better than their parents in quality. Relative-risk assessment allows for the continuation of lines that might otherwise be abandoned due to high carrier risk.

Breeding a dog only once and replacing it with an offspring allows breeders to improve their chances of moving away from defective genes and also limits the dissemination of defective genes. When dealing with disorders for which carriers cannot be identified, the number of offspring placed in breeding homes should be kept to a minimum.

Autosomal Dominant Disorders

Autosomal dominant genetic disorders are usually easy to manage. Each affected dog has at least one affected parent, but it can be expected that half of the offspring of an affected dog will be free of the defective gene. With disorders that cause death or discomfort, the recommendation is to not breed affected dogs. To produce the next generation of a line, a normal full sibling of an affected dog can be used, or the parent that is normal can be used.

A problem with some autosomal dominant disorders is incomplete penetrance. In other words, some dogs with the defective gene may not show the disorder. Roughly half their offspring, however, may be affected. If a genetic test is available, this is not a problem. Otherwise, relative-risk assessment can identify which dogs are at risk of carrying incompletely penetrant dominant genes.

Sex-Linked Disorders

For sex-linked (also known as x-linked) recessive defective genes for which carrier tests exist, breeders should follow the same “breed and replace” recommendations as are outlined above in the discussion of autosomal recessive disorders. If there is no test, the defective gene can be traced through the pedigree. If a male is affected, he would have received the defective gene from his carrier mother. All of his daughters will be carriers, but none of his sons. By using relative-risk assessment to breed him to a female that is at low risk of being a carrier, you can prevent affected offspring, and select a quality son for replacement. 

There are rare instances in which a female is affected with a sex-linked disorder. In such cases, she would have received the defective gene from both parents; specifically, an affected father and a mother who is either a carrier or is affected herself. If an affected female is bred, all the sons will be affected, and all the daughters would be carriers, so affected females clearly should not be bred. A normal male that is a littermate to an affected female, however, would be able to carry on the line without propagating the defective gene.

Sex-linked dominant disorders are managed the same way as autosomal dominant disorders are. The difference is that affected males will always produce all affected daughters.

Polygenic disorders

Polygenic disorders are those caused by more than one pair of genes. Most polygenic disorders have no tests for carriers, but they do have phenotypic tests that can identify affected dogs. (For a detailed discussion of polygenic disease management, see “Choosing Wisely” in the August 2000 AKC Gazette.)

With polygenic disorders, a number of genes must combine to cross a threshold and produce an affected dog. These are known as liability genes.  In identifying a dog’s liability for carrying defective genes for a polygenic disorder, the breadth of the pedigree (that is, consideration of all siblings of individuals in the pedigree) is more important than the depth of the pedigree (consideration only of parent-offspring relationships.) A clinically normal dog from a litter that had one or no individuals affected with hip dysplasia (which is a polygenic disorder) is expected to carry a lower amount of liability genes than a dog with a greater number of affected littermates. This is why it is important to screen both pet and breeding dogs from your litters for polygenic disorders. Information on the siblings of the parents of potential breeding dogs provides additional data on which to base your breeding decisions.

Genetic disorders without a known mode of inheritance should be managed in the same way as polygenic disorders. If there are multiple generations of normalcy in the breadth of the pedigree, then you can have some confidence that there is less risk that liability genes are being carried. If a dog 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 tests are extremely useful tools to help manage genetic disorders. Even when there is no test, or a known mode of inheritance, much can still be done to reduce the incidence of affected and carrier animals. The use of these guidelines can assist breeders in making objective breeding decisions for genetic-disease management, while continuing their breeding lines.

Genetic Testing and Genetic Counseling in Pet and Breeding Animals
Jerold S. Bell, DVM, Tufts University School of Veterinary Medicine
Jerold.Bell@tufts.edu

Genetic testing and genetic counseling are not just for breeding animals. They include; testing for the bleeding disorder von Willebrand’s disease before performing surgery on susceptible breeds, altering diets for pets that are prone to developing bladder stones or crystals, and switching from rapid growth puppy food to lower calorie foods in young, large breed dogs, so that joint tissues can develop at a more uniform rate.

The hallmark of genetic disease is the ability to predict disease before its onset. This allows the possibility of medical or surgical intervention in order to prevent later suffering. Knowledge of breed-related genetic disease and the tests that are available permit early diagnosis and treatment.

Breeders and veterinarians have been utilizing genetic tests since the beginning of domestic animal breeding. Most genetic tests measure the phenotype of an animal, or what you can see. These include radiographs, blood values, eye examinations, skin biopsies, urinalysis for crystals or metabolites, observations on structure or behavior, and ausculting for heart murmurs. Most tests of the phenotype only identify affected individuals, and not carriers. These may, or may not directly relate to the genotype, or the genes regulating the defect.

A test of the genotype is one that assesses the DNA of the animal. These tests can be run at any age, regardless of the age of onset of the disorder. Utilizing polymerase chain reaction (PCR) technology, affected, carrier, and normal individuals can be identified. As the majority of genetic disorders are recessive or have a major recessive component, the identification of carriers is important for effective management.

As additional DNA tests are developed for disorders, the role of genetic counseling becomes more important. Without these tests, the number of individuals that can be identified as carriers is low, even though many may be suspect due to having affected relatives. Breeds have closed gene pools; in other words, the diversity of genes in a given breed is fixed. The number of individuals removed from consideration for breeding based on concerns regarding a specific genetic disease is usually low. While this has slowed the management of genetic disease, it has also prevented genetic drift and diversity problems for pure breeds.

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: 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, creating bottlenecks and diminishing diversity by eliminating all carriers of a gene from the breeding pool, instead of breeding and replacing them, and concentrating on the presence or absence of a single gene and not the quality of the whole animal.

DNA tests have to be developed specifically for each breed (or group of related breeds that share an ancestral mutation). There are two different types of tests of the genotype; direct gene tests and linkage-based tests. Direct gene tests check for a specific mutation in a defective gene. The animal either carries the defective gene, or does not.

Linkage-based DNA tests can be developed even if the defective gene causing a disorder has not been identified. Genome research has identified thousands of genetic markers, or “marker-DNA” that are spread across the chromosomes of the species. A linked-marker is a piece of DNA that lies close to the defective gene on a chromosome. 

Breeders can use linkage-based genetic tests the same way direct genetic tests are used. The only difference is that you are not directly testing for the defective gene, only an associated marker; so false-positive and false-negative test results can occur.

A genetic crossover between paired chromosomes mixes the genes that an individual receives from its sire and dam. This occurs on a regular basis during the formation of eggs and sperm. As a defective gene and the linked marker are different areas of DNA that lie close together on a chromosome, it is possible that a genetic crossover can occur between them. This would separate the marker from the defective gene and create false positive (testing for the marker without the defective gene), or false negative (testing as normal, but having the defective gene) results. Depending on the relative distance between the marker and the defective gene on the chromosome, researchers can predict the frequency of false results for a linkage-based test; for example: 1 in 100.

If an individual’s linkage-based test for the defective gene is producing false-positive or false-negative results, all of its descendents that inherit this portion of the chromosome will also have false test results. This has been documented with families of Bedlington Terriers tested for the autosomal recessive copper toxicosis gene.

It is obvious that direct gene tests are better than linkage-based tests. However, a test with 90% or 95% confidence is better than no test at all. As genomic research progresses, researchers can identify the defective genes responsible for disorders, and can develop direct gene tests to replace linkage-based tests. The defective gene for copper toxicosis in the Bedlington Terrier has now been identified, and a direct gene test is now possible.

Based on the mode of inheritance of a disorder, and the availability of genotypic or phenotypic genetic tests, breeding management recommendations can be used to prevent or reduce the frequency of carrier or affected offspring. See the article “Breeding Strategies for the Management of Genetic Disorders” in the proceedings for specific recommendations.

Once a genetic test is developed, it allows breeders to positively determine if an individual is a carrier of a defective gene. The typical response of a breeder on finding that their animal is a carrier is to remove it from a breeding program. If a majority of breeders do this, it puts the breed’s gene pool through a genetic bottleneck that can significantly limit the diversity of the breed. The goal of genetic testing is to allow the superior genes of a breeding individual to be propagated, even if the animal is a carrier. 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. If an owner would breed an individual if it tested normal for a genetic disease, then a carrier result should not change that decision.

Owners of carrier animals who are of breeding quality in other health, temperament, performance and conformation aspects should be bred to normal testing mates. This prevents the production of affected offspring. The breeder should be counseled to test the offspring prior to placement; to determine whether a pet or breeding home is appropriate. The goal is to replace the carrier parent with a quality, normal testing offspring that carries on the lineage of the breeding program. 

If the only quality offspring is also a carrier, then breeders can use that offspring to replace the original carrier. The breeder has improved the quality of the breeding stock, even though the defective gene remains in the next generation. The health of the breed does depend on diminishing the carrier frequency and not increasing it. Breeders should therefore limit the number of carrier-testing offspring placed in breeding homes.  It is important to carry on lines. A test that should be used to help maintain breed diversity should not result in limiting it.

By breeding and not selecting against carriers, breeders are selecting for a carrier frequency of fifty-percent; higher than most breed averages. Each breeder must assess the frequency of the defective gene in their own breeding stock and determine their own rate of progress. As each breeder reduces the number of carrier breeding stock, the frequency of the defective gene for the breed will decrease.

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. Remember, however, that an animal is not a single gene, an eye, a hip, or a heart. Each individual carries tens of thousands of genes, and each is a part of the breed's gene pool. When considering a mating, breeders must consider all aspects - such as health issues, conformation, temperament and performance - and weigh the pros and cons.

Without tests, the management of genetic disease involves breeding higher-risk animals to lower-risk animals. Occasionally, a breeding male is determined to not carry a defective gene for which there is no carrier test. The tendency is for everyone to breed to this male, as a guarantee against the disorder. Any major shift in the breeding choices to a limited number of males will restrict genetic diversity, and increase the possibility of propogating additional undetected defective recessive genes in a breeding population. Such genes have become widespread even in populous breeds due to prolific breeding of popular sires.

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. Breeders should be counseled on how to utilize test results for the best interests of the breed.

Pedigree Analysis, and How Breeding Decisions Affect Genes
Jerold S. Bell, DVM, Tufts University School of Veterinary Medicine
Jerold.Bell@tufts.edu

To some breeders, determining which traits will appear in the offspring of a mating is like rolling the dice a combination of luck and chance. For others, producing certain traits involves more skill than luck the result of careful study and planning. As breeders, you must understand how matings manipulate genes within your breeding stock to produce the kinds of offspring you desire. First comes understanding dogs and cats as species, then as genetic individuals.

There is little similarity between a Chihuahua and a Saint Bernard, or between a Himalayan and a Sphynx. However, we must understand that while established breeds are separate entities among themselves, they all are genetically the same species. While a mating within a breed may be considered outbred, it still must be viewed as part of the whole genetic picture: a mating within an isolated, closely related, interbred population. Each breed was developed by close breeding and inbreeding among a small group of founding ancestors, either through a long period of genetic selection or by intensely inbreeding a smaller number of generations. This process established the breed's characteristics and made the individuals in it breed true.

Pure-breeds have closed stud books. This means that the diversity of genes in the breed is fixed. Genes cannot be gained through breeding, only lost. In some cat breeds, cats who meet the phenotypic standard of the breed may be introduced into the gene pool. This, of course is an added source of genetic diversity for the breed.

When evaluating your breeding program, remember that most traits you're seeking cannot be changed, fixed or created in a single generation. The more information you can obtain on how certain traits have been transmitted by your animal's ancestors, the better you can prioritize your breeding goals. Tens of thousands of genes interact to produce a single individual. All individuals inherit pairs of chromosomes; one from the mother, and one from the father. On the chromosomes are genes; so all genes come in pairs. If both genes in a gene pair are the same gene (for instance, “aa” or “AA”) the gene pair is called homozygous. If the two genes in a gene pair are unlike (for instance, “Aa”) the gene pair is called heterozygous. Fortunately, the gene pairs that make a cat a cat and not a dog are always homozygous. Similarly, the gene pairs that make a certain breed always breed true are also homozygous. Therefore, a large proportion of homozygous non-variable pairs - those that give a breed its specific standard - exist within each breed. It is the variable gene pairs, like those that control color, size and angulation that produce variations within a breed.

There are ways to measure the genetic diversity of a population. One method is to measure the average inbreeding coefficient (or Wright’s coefficient) for a breed. The inbreeding coefficient is a measurement of the genetic relatedness of the sire and dam. If an ancestor appears on both the sire and dam’s side of the pedigree, it increases the inbreeding coefficient. The inbreeding coefficient gives a measurement of the total percentage of variable gene pairs that are expected to be homozygous due to inheritance from ancestors common to the sire and dam. It also gives the chance that any single gene pair can be homozygous.

The types of matings that you choose for your breeding animals will manipulate their genes in the offspring, affecting their expression. Linebreeding is breeding individuals more closely related (a higher inbreeding coefficient) than the average of the breed. Outbreeding involves breeding individuals less related than the average of the breed. Linebreeding tends to increase homozygosity. Outbreeding tends to increase heterozygosity. Linebreeding and inbreeding can expose deleterious recessive genes through pairing-up, while outbreeding can hide these recessives, while propagating them in the carrier state. 

Most outbreeding tends to produce more variation within a litter. An exception would be if the parents are so dissimilar that they create a uniformity of heterozygosity. This is what usually occurs in a mismating between two breeds, or a hybrid, like a Cockapoo. The resultant litter tends to be uniform, but demonstrates "halfway points" between the dissimilar traits of the parents. Such litters may be phenotypically uniform, but will rarely breed true due to the mix of dissimilar genes.

One reason to outbreed would be to bring in new traits that your breeding stock does not possess. While the parents may be genetically dissimilar, you should choose a mate that corrects your breeding animal's faults but phenotypically complements its good traits. It is not unusual to produce an excellent quality individual from an outbred litter. The abundance of genetic variability can place all the right pieces in one individual. Many topwinning show animals are outbred. Consequently, however, they may have low inbreeding coefficients and may lack the ability to uniformly pass on their good traits to their offspring. After an outbreeding, breeders may want to breed back to individuals related to their original stock, to attempt to solidify newly acquired traits.

Linebreeding attempts to concentrate the genes of specific ancestors through their appearance multiple times in a pedigree. It is better for linebred ancestors to appear on both the sire's and the dam's sides of the pedigree. That way their genes have a better chance of pairing back up in the resultant offspring. Genes from common ancestors have a greater chance of expression when paired with each other than when paired with genes from other individuals, which may mask or alter their effects.

Linebreeding on an individual may not reproduce an outbred ancestor. If an ancestor is outbred and generally heterozygous (Aa), increasing homozygosity will produce more AA and aa. The way to reproduce an outbred ancestor is to mate two individuals that mimic the appearance and pedigree of the ancestor's parents.

Geneticists' and breeders' definitions of inbreeding vary. A geneticist views inbreeding as a measurable number that goes up whenever there is a common ancestor between the sire's and dam's sides of the pedigree; a breeder considers inbreeding to be close inbreeding, such as fathertodaughter or brothertosister matings. A common ancestor, even in the eighth generation, will increase the measurable amount of inbreeding in the pedigree.

Inbreeding significantly increases homozygosity, and increases the expression of both desirable and deleterious recessive genes through pairing up. If a recessive gene (a) is rare in the population, it will almost always be masked by a dominant gene (A). Through inbreeding, a rare recessive gene (a) can be passed from a heterozygous (Aa) common ancestor through both the sire and dam, creating a homozygous recessive (aa) offspring. 

To visualize some of these concepts, the pedigree of a Gordon Setter, Laurel Hill Braxfield Bilye will be used. The paternal grandsire, CH Loch Adair Foxfire, and the maternal grandam, CH Loch Adair Firefly WD, are full siblings, making this a firstcousin mating. The inbreeding coefficient for a first cousin mating is 6.25%, which is considered a mild level of inbreeding.

In Bilye’s pedigree, an inbreeding coefficient based on four generations computes to 7.81%. This is not significantly different from the estimate based on the firstcousin mating alone. Inbreeding coefficients based on increasing numbers of generations are as follows: five generations, 13.34%; six generations, 18.19%; seven generations, 22.78%; eight generations, 24.01%; ten generations, 28.63%; and twelve generations, 30.81%. The inbreeding coefficient of 30.81 percent is more than what you would find in a parenttooffspring mating (25%). 

The total inbreeding coefficient is the sum of the inbreeding from the close relatives (first cousin mating), and the background inbreeding from common ancestors deep in the pedigree. Such founding ancestors established the pedigree base for the breed. The background inbreeding has far more influence on the total inbreeding coefficient than the firstcousin mating, which only appears to be its strongest influence.

Knowledge of the degree of inbreeding in a pedigree does not necessarily help you unless you know whose genes are being concentrated. The relationship coefficient, which can also be approximated by what is called the percent blood coefficient, represents the probable genetic likeness between the individual whose pedigree is being studied, and a particular ancestor. It is a measurement of the average percentage of genes the individual and the ancestor should have in common.

We know that a parent passes on an average of 50% of its genes, while a grandparent passes on 25%, a greatgrandparent 12.5%, and so on. For every time the ancestor appears in the pedigree, its percentage of passedon genes can be added up and its "percentage of blood" estimated. In many breeds, an influential individual may not appear until later generations, but then will appear so many times that it necessarily contributes a large proportion of genes to the pedigree. This can occur in breeds, due either prolific ancestors (usually males), or a small population of animals originating the breed. Based on a twenty-five generation pedigree of Bilye, there are only 852 unique ancestors who appear a total of over twenty-million times.

In Bilye’s pedigree, CH Afternod Drambuie has the highest genetic contribution of all of the linebred ancestors. He appears 33 times between the sixth and eighth generations. One appearance in the sixth generation contributes 1.56% of the genes to the pedigree. His total contribution is 33.2% of Bilye’s genes, second only to the parents. Therefore, in this pedigree, the most influential ancestor doesn't even appear in a five-generation pedigree. His dam, CH Afternod Sue, appears 61 times between the seventh and tenth generations, and contributes more genes to the pedigree than a grandparent.

Foundation dogs that formed the Gordon Setter breed also play a great role in the genetic makeup of today’s dogs. Heather Grouse appears over one million times between the sixteenth and twenty-fifth generations, and almost doubles those appearances beyond the twenty-fifth generation. He contributes over ten percent of the genes to Bilye’s pedigree. This example shows that the depth of the pedigree is very important in estimating the genetic makeup of an individual. Any detrimental recessive genes carried by Heather Grouse or other founding dogs, would be expected to be widespread in the breed.

The average inbreeding coefficient of a breed is a measurement of the breed’s genetic diversity. When computing inbreeding coefficients, you have to look at a deep pedigree to get accurate numbers. An inbreeding coefficient based on 10-generation pedigrees is standardly used, but requires a computerized pedigree database to compute.

The average inbreeding coefficient for a breed will be based on the age and genetic background of the breed. A mating with an inbreeding coefficient of 14 percent based on a ten generation pedigree, would be considered moderate inbreeding for a Labrador Retriever (a popular breed with a low average inbreeding coefficient), but would be considered outbred for an Irish Water Spaniel (a rare breed with a higher average inbreeding coefficient).

Looking at the historical pedigrees of Bull Terrier breeding dogs (males and females that have five or more registered offspring), we find that for dogs born in the decade 1970-1979, the average ten generation inbreeding coefficient was 23.11% +/- 6.04%. For Bull Terriers born 1980-1989, this number is 21.54% +/- 5.69%. For 1990-1999, the average inbreeding coefficient is 19.01% +/- 6.23. It is obvious that the 10 generation inbreeding coefficient of the Bull Terrier breed is going down with each decade. This shows that the breeders are utilizing the diversity of the gene pool, and not breeding themselves into a corner with popular sires.

Of course, the actual diversity of genes and inbreeding in the breed is not going down It is just that the earlier ancestors producing background inbreeding are falling beyond the 10^th generation, and are no longer included in the computation. As long as the health and vitality of the breed is being maintained, and there is no epidemic of breed-related disease from detrimental recessives, this pure-bred population should be able to be maintained.

Most breeds start from a small founding population, and consequently have a high average inbreeding coefficient. If the breed is healthy and prolific, the breadth of the gene pool increases, and the average inbreeding coefficient can go down over time. Some dog breeds were established on a working phenotype, and not on appearance. These breeds usually start with low inbreeding coefficients due to the dissimilar backgrounds of the founders. As certain individuals are linebred on to create a uniform physical phenotype, the average inbreeding coefficient can increase.

There is no specific level or percentage of inbreeding that causes impaired health or vigor. 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. There are pure-bred populations where smaller litter sizes, shorter life expectancies, increased immune-mediated disease, and breed-related genetic disease are plaguing the population. In these instances, prolific ancestors have passed on detrimental recessive genes that have increased in frequency and homozygosity. With this type of documented inbreeding depression, it is possible that an outbreeding scheme could stabilize the population. However, it is also probable that the breed will not thrive without an influx of new genes; either from a distantly related (imported) population, a natural landrace population, or crossbreeding.

Fortunately, most breeds do not find themselves in the position of this amount of limited diversity and inbreeding depression. However, the perceived problem of a limited gene pool has caused some breeders to advocate outbreeding of all individuals. 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. Eventually, there will not be any “unrelated line” to be found. Everyone will have a mixture of everyone else’s genes. This practice in livestock breeding has significantly reduced diversity, and caused the loss of unique rare breeds.

A fallacy of using outbreeding to maintain genetic diversity is the belief that the diversity of a breed must be maintained in every single animal. Breeders must concentrate on the specific goals of breeding (selecting for the health and quality of the breed), versus the tools used to get there (outbreeding, linebreeding, etc.) Selecting breeding stock simply to produce the lowest possible inbreeding coefficient is not a goal that will guarantee a quality animal. Animals who are poor examples of the breed should not be used simply to maintain diversity. Related individuals with desirable qualities will maintain diversity, and improve the breed. 

The process of maintaining healthy “lines” or families of animals, with many breeders crossing between lines (outbreeding) and breeding back (linebreeding) as they see fit maintains diversity in the gene pool. It is the varied opinion of breeders as to what constitutes the ideal representative of the breed, and their selection of breeding stock that maintains breed diversity. 

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. Selection, and not the types of matings used affect gene frequencies and breed genetic diversity.

If two parents are both heterozygous (both Aa) for a gene pair, on the average, they would produce 25% AA, 50% Aa, and 25% aa. (These are averages when many litters are combined. In reality, any variety of pairing up can occur in a single litter.) If a prolific male comes out of this litter, and he is homozygous aa, then the frequency of the “a” gene will increase in the population, and the frequency of the “A” gene will decrease. This is known as the popular sire syndrome. Of course, each individual has thousands of genes that vary in the breed, and everyone carries some deleterious recessive genes. The overuse of individual breeding animals contributes the most to decreased diversity (population bottlenecks), and the increased spread of deleterious recessive genes (the founders effect). Again, it is selection (use of this stud 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 lines, so as to not create new genetic bottlenecks.

Decisions to linebreed, inbreed or outbreed should be made based on the knowledge of an individual's traits and those of its ancestors. Inbreeding will quickly identify the good and bad recessive genes the parents share, based on their expression in the offspring. Unless you have prior knowledge of what the offspring of milder linebreedings on the common ancestors were like, you may be exposing your litters (and 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 longrange 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 homozygousdominant (AA) individuals. Desirable recessive traits can be fixed in one generation because individuals that show such characteristics are homozygous for the recessive genes. Individuals that pass on desirable traits 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. However, these individuals should not be overused, to avoid the popular sire syndrome.

Breeders should plan their matings based 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 for desirable traits, and against detrimental traits will allow greater control.