Jerold S. Bell, DVM
Dept. of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, N. Grafton, MA, USA
Pure-bred dog and pedigreed cat breeds developed through distinct selective pressures. Some breeds began as inbred populations from limited founders that expanded their gene pools over time. Others began as outbred populations with a working or conformational phenotype. Regardless of the background of the founders, high inbreeding coefficients and low effective population size occur early in breed development. The "background inbreeding" on the founders establishes the basis for the breed, and its positive and negative genetic contributions. As the population expands within a closed gene pool, mating choices allow matings between individuals who are less closely-related than prior generations. With a progressively smaller percentage of the population reproducing, the chance for genetic drift and within-breed stratification increases.
When studying Wright's inbreeding coefficients (IC) of populations, a set number of generations (for example 10) should be used to compute the IC. In this way, generations can be compared to see whether the breed is utilizing the breadth of its gene pool, or narrowing its diversity into a small subpopulation.
The popular sire effect is the most important factor in changing allele frequencies, genetic diversity, and disease propagation in dog and cat breeds. The overuse of prolific sires truncates the gene pool (population bottlenecks) to major lines of descent. The popular sire is a proliferator of both positive and deleterious alleles, thus increasing their frequency in the population. The insidious effect of the popular sire syndrome is that it diminishes the contribution of other worthy males, thus reducing diversity and the effective population size.
Studies of dog and cat populations focus on the inbreeding that established the breeds, and the presence of breed-related genetic disease. Breed-related genetic disease is due to ancestral deleterious alleles in founders or more recent mutations dispersed through popular sires. Different mating types (inbreeding, linebreeding, outbreeding) are responsible for the expression of alleles in gene pairs, but not in allele propagation. Selection of breeding stock for the next generation, and their fecundity is what alters allele frequencies. A mix of breeding individuals from different lines within the breed maintains allelic polymorphism.
The Nova Scotia Duck Tolling Retriever breed developed based on a working phenotype from diverse founder breeds in the early 1900s. Ten generation inbreeding coefficients peaked in the 1980s. Twenty-five ancestors contributed to the present day population, with two founders explaining 50% of the variation in the breed. Unfortunately, founding individuals passed on several anciently mutated disease-causing genes including: collie eye anomaly/choroidal hypoplasia (2% affected, 16% carrier), the prcd form of progressive retinal atrophy (6% affected, 45% carrier), and hereditary Addison's disease (hypoadrenocorticism; 1.4% affected). To maintain genetic diversity, breeders must breed quality carriers to normals, and replace carriers with normal testing offspring.
The American Burmese cat breed originated in the early 1930s based on inbreeding on a single female. Ten generation inbreeding coefficients peaked in the 1960s. In the 1970s, a line of Burmese with rounded heads was linebred on to create what is called the "contemporary" (versus traditional) head type. Unfortunately, the contemporary "round" head is due to the heterozygous expression of an incompletely dominant gene that causes a lethal cranial-facial defect in the homozygous state. Other breeds whose head structure is similar to the contemporary Burmese head type do not carry the gene for the head deformity (genocopies). It is possible that over decades of selection for the contemporary head type, breeders have selected for genocopies that are not related to the head deformity gene. A genetic test will be useful for breeders to determine who carries the defective gene. Both the overuse of contemporary type Burmese without the defective gene (popular sire effect) and wide scale elimination of quality lines with the defective gene will significantly limit the Burmese gene pool, and significantly impact the genetic diversity of the breed.
The Cavalier King Charles Spaniel was "recreated" in the late 1920s from the short-nosed King Charles Spaniel to restore its ancestral head conformation. Ten generation inbreeding coefficients peaked in the 1980s. Chiari-like (occipital bone) malformation occurs in 95% of the breed. Approximately 50% of the breed can develop MRI signs of syringomyelia - a fluid filled cavity in the cervical spinal cord. Approximately 17.5% of the breed can develop pain and neurological signs from SM. Mitral valvular heart disease develops in 56% of the breed by age 4, and in 98% of the breed by age 10. Breed improvement depends on genetic screening for the disorders.
The genetic health of dog and cat breeds is not a direct function of homozygosity or heterozygosity; but of the accumulation and propagation of disease causing genes. Only a limited number of individuals are selected to reproduce in a non-random manner to create the next generation. This results in linkage disequilibrium and the propensity for significant rapid changes in allele frequencies. Any efforts to manage breed-related genetic disease must focus on genetic testing and selection. Genetic counseling recommendations should include considerations of how individual breeding decisions will affect the overall gene pool of breeds.