Jerold S. Bell, DVM
Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA
In order to understand the genetic consequences of breed formation, one must understand the population dynamics involved in the evolution of species, and then the artificial selection that creates breeds.
Species develop through natural selection. Any genetic changes that occur within a population that improve the chance of survival and ability to reproduce in the populated environment will drive evolution. Lines that do not evolve and become disadvantaged will diminish in influence and often die out.
The development and proliferation of "specialists" who are more capable of living and reproducing through natural selection result in a loss of genetic diversity through the disadvantaged. Any selection, whether natural or artificial, will cause a loss of genetic diversity.1,2 This loss is not detrimental to the population, as it is directly related to increasing its superiority.
Canis familiaris developed to live alongside man with a plasticity of behavior and morphology to perform various tasks. These behaviors involved honing their natural abilities at hunting, guarding, hearing, scenting, and protection. Through artificial selection of individuals that were best at performing the associated task, lines of dogs developed that differentiated themselves from others. Morphological features that improved these abilities increased the physical difference between lines such as the speed and ability of hunting dogs versus the strength and durability of dogs of war (mastiff breeds).3 The later separation of task-associated groups into breeds occurred with further restrictions along conformational and behavioral standards.
Felis catus developed to live alongside man for its ability at rodent control and companionship. The development of breeds occurred through natural selection for body type, color, coat type, behavior, and other conformational aspects.4
Dog and cat lines that did not perform, adhere to an artificial standard, or that were at a selective disadvantage were abandoned along with their unique genetic backgrounds. As lines became more specialized and stud books closed, genetic diversity became more restricted.
Some feel that any loss of genetic diversity is detrimental to any population. This view is diametrically opposed to the continued sustainability of artificial breeds. Breeds do not have the same population dynamics of natural populations. With breed populations, a much smaller percentage of individuals reproduce to create the next generation. When selection is done properly, those that reproduce have identifiable qualities over those that do not. The rest of the population is lost to the gene pool. There will always be a loss of genes and genetic diversity.
The health and vitality of a breed depend on its ability to live, reproduce, and perform the expected function determined by man, unbridled by genetic disease. It is important that breed standards and selection practices specifically avoid selection for extreme phenotypes and disease liability.
Population dynamics must allow that the individuals chosen for breeding represent the quality traits of the breed, and that these quality traits are not lost through genetic drift or abandonment of quality lines. Studies show that genetic health is not correlated to the genetic diversity of the breed, the population size, or inbreeding, but to the presence of specific disease liability genes.1,5-7
Population expansion is an important aspect of breed development and maintenance. It allows the creation of new "family lines" and within-breed diversity. Population contraction is detrimental to breed maintenance due to the loss of quality breeding lines and genetic diversity. Healthy breed gene pools require expanding, or large stable populations.
Diseases and Disorders - The Dark Side of Breed Development
Deleterious genes can increase in frequency with natural as well as artificial selection. More "lines" of naturally occurring species have died off due to genetic disorders or diminished fitness compared to those that have survived. All individuals carry some deleterious mutations. As individuals who carry quality traits propagate, they will also propagate their deleterious mutations. Through the founder's effect, these mutations can become breed-related disease if they are disseminated and increase in frequency.
Studies show that some breeds have more issues of specific genetic diseases with homozygosity and others do not.1,8-10 This depends on the genetic load of deleterious recessive genes in the gene pool. A molecular genetic study of lymphoma susceptibility in Golden Retrievers showed that liability is individual and not just a breed risk.11 Some breeds may show decreased litter size, increased neonatal mortality, or shorter average life spans due to the homozygous expression of specific deleterious genes that cause specific disease. The genetic health of dog and cat breeds is not a direct function of homozygosity or heterozygosity, but of the accumulation and propagation of specific disease liability genes.
Selection for positive breed traits will always precede selection against deleterious recessive genes, as these will not become apparent until they are exposed through homozygosity. Artificial selection to maintain breeds requires active selection against deleterious genes. For dominant and additive genes - where the genotype is represented in the phenotype - this is an expected component of selection. For recessive deleterious genes, selection involves the development and use of genetic tests that reveal the carrier state or the discrimination of lines with carrier risk. Breed propagation must always include active monitoring and selection against genetic disease. Without this selection, the genetic health of the breed will decline.
Pedigree Analysis of Populations
When deep pedigree databases of dog and cat breeds are analyzed, it is found that ancestral family lines during breed formation are often abandoned due to the expression of deleterious or undesirable traits. It is only the lines that produce the desired characteristics and thrive through matings and generations of breeding that become the mainstream ancestral "founders" of a breed. All breeds go through this growth and purging process.
Modern breed population statistics show high total population inbreeding coefficients, low effective population size, and high average relationship coefficients to influential ancestors whose generations of descendants have epitomized the breed.12 These influential ancestors will appear deep in the pedigree of every member of the breed, but will appear so many times that their genetic contribution will often equal those in the second (~ 25%) or third (~ 12.5%) generation.
For example in the Burmese breed, all cats have an average relationship coefficient (gene sharing) to: the breed founder Wong Mau of 30.71%, to Antonica Pamphula of Mizpah (1956) of 25.07%, to Gerstdale Sealskin Jacket (1947) of 22.30%, and to three others with average relationship coefficients over 20%. In the Cavalier King Charles Spaniel, all dogs have an average relationship coefficient to: Daywell Roger (1945) of 32.52%, to Cannonhill Richey (1941) of 30.42%, to Ann's Son (1927) of 26.27%, and to three others with average relationship coefficients over 20%.
Modern breeds of cats and dogs are in various stages of expanding their population and gene pools. Some breeds may have smaller effective population sizes and higher generational inbreeding coefficients. However, if their offspring are generally healthy their population can grow and expand. They are at stages of breed development where more populous breeds were earlier in their development.
With an expanding breed population, ten generation inbreeding coefficients usually decrease as the average genetic relationship between mates becomes less than in the previous generation. The exception to this is when breeders are concentrating on popular sires or sire lines. In these situations, other quality male lines are abandoned and (genetic diversity) lost to the breed gene pool in exchange for a rapidly increasing influence of the popular sire.13 The popular sire syndrome is the single most influential factor in restricting breed gene pool diversity.
There is a difference between a popular sire gaining significant average relationship to the breed population and that of an influential ancestor. The influential ancestor's contribution is continually evaluated with each generation of their descendants for the presence of quality and absence of defect. Each generational descendent must demonstrate their superiority over other individuals to maintain breeding status. A popular sire's genetic influence can only be evaluated after its genes have been widely disseminated; when its recessive influences are exposed. If there are issues with quality or defect, it is more difficult to reverse a popular sire's influence. Purging a popular sire's lines also results in the loss of influence of the assorted quality dam lines he was bred to.
Molecular Genetic Analysis of Breeds
The process of breed formation creates "selective sweeps" where large chromosomal segments surrounding breed-defining genes become homozygous and fixed in the population. These include selected genes controlling phenotypes for size, coat color and texture, behavior, skeletal morphology, and other breed-specific characteristics.14-16 Similar selective sweeps are found in cattle breeds.17,18
Molecular genetic studies of the chromosomal structure of breeds shows these large haplotype blocks (identical sections of chromosomes) and linkage disequilibrium (LD) representing the results of inbreeding and purging during breed development.19,20 Studies of dog breeds estimate that they lose on average 35% of their genetic diversity through breed formation.21
Molecular genetic studies of breeds document the homozygosity that mirrors the pedigree-based total inbreeding coefficients and common ancestral relationship coefficients. These changes occur due to selection and are an expected prerequisite and consequence of breed formation. Homozygosity is not inherently correlated to impaired genetic health nor does it need to be artificially controlled.
Expanding populations with different breeders undertaking different types of matings and selecting on different lines, while monitoring and selecting against genetic disease provides for a healthy, diverse breed gene pool.
Some advocates more versed in endangered species preservation call for outbreeding programs in an effort to "rescue" breeds. Genetic diversity involves breeding representatives from diverse areas of the gene pool, but not necessarily the types of matings (outbreeding versus linebreeding) that they are involved in. Outbreeding will not diminish the expression of breed-related genetic disease, as the causative genes are already dispersed in the population.
Some call for programs to increase minor allele frequencies. However, it is just as likely that genetic selection for quality and against undesirable traits is what reduced the frequency of these alleles in the first place. Blindly selecting for them without knowing their effect could significantly reverse selection-based breed improvement. This has been shown in cattle breeds.22
Some call for programs to increase diversity of MHC haplotypes to improve the immune system of breeds. In no breeds has general limited diversity or random homozygosity of MHC haplotypes shown to impair an individual's immunity. All molecular genetic studies of autoimmune disease, immune deficiency or pathogen susceptibility identify specific disease-related genes or MHC haplotypes, and not necessarily the MHC diversity or homozygosity of any random haplotype.23 Some disease-associated MHC haplotypes require homozygosity, and some require only one copy of the haplotype to confer disease risk.24,25 Other immune-mediated diseases are linked to specific genes outside the MHC complex.26,27
Most cat and dog breeds show adequate diversity and do not show signs of genetic depletion requiring rescue protocols. Breed maintenance requires:
A large or expanding breed population
Avoidance of extreme phenotypes that can produce disease liability
Monitoring of health issues in the breed
Avoidance of the popular sire syndrome
Constant selection for quality and health
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