Jerold S. Bell, DVM
Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton, MA, USA
(This article is based on a poster presented at the 7th International Conference on Advances in Canine and Feline Genomics and Inherited Diseases, Sweden, 2012. It can be reproduced with the permission of the author.)
Breed Gene Dynamics
Each dog and cat breed has its own evolutionary history of founders, accumulated deleterious genes, population bottlenecks, popular sires, and geographical fragmentation. Some studies of dog and cat breeds focus on the inbreeding coefficients of individuals, and the effective population size of breeds as a measurement of their genetic vitality and ability to maintain themselves as pure breeds (Calboli et al. Genetics. 2008;179:593–601).
Most breeds started from a limited number of founders. As the population expands within a closed gene pool, it allows mating choices between individuals that are less closely related than the previous generation. This is shown by evaluating average 10 generation inbreeding coefficients (Mean 10 Gen IC). Early in breed development, inbreeding coefficients can be high due to inbreeding on a small founder population (as seen in the Borzoi and Burmese breeds), or breeding with a more diverse founder population (as seen in the Siberian Husky, Gordon Setter, and Cavalier King Charles Spaniel breeds).
As generational pedigrees extend beyond 10 generations, the IC Mean 10 Gen can decrease as populations utilize the breadth of their gene pool and the number of unique ancestors increase. When the Mean 10 Gen IC increases, it is usually because breeders are concentrating on popular sires. The Mean All Gen IC (homozygosity) necessarily goes up over time as a function of breed evolution. (The Mean All Gen IC of Burmese goes down in this example due to importation of Burmese with incomplete pedigrees.) 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 liability genes.
Several researchers have found that dog breed genetic diversity is not a function of population size or average inbreeding levels (James. Vet J. 2011;189:211–213; Bjornerfeld et al. BMC Evol Biol. 2008;8:28). Shariflou et al. (Vet J. 2011;189:203–210) found that genetic diversity is not related to the size of the breed, but to breeding practices and the even contribution of founding lines. The popular sire syndrome is the single most influential factor in restricting breed gene pool diversity.
Molecular genetic studies of cattle show limited genetic diversity in evolutionary founder populations (Bollongino et al. Mol Biol Evol. 2012;29(9):2101–2104; The Bovine HapMap Consortium. Science. 2009;324(5926):528–532). In spite of this, cattle breeds have propagated and are second only to dogs in mammalian genetic diversity.
Breed genetic health does not have to do with existing breed inbreeding coefficients, homozygosity, estimated number of founders, or other statistics. It has to do with reproductive ability and accumulated disease liability genes. Breed genetic health should be judged based on current breed health surveys.
Some organizations have embraced the belief that close breeding is the cause of impaired breed health. They have adopted programs that restrict close breeding and promote outbreeding to the least-related individuals. This involves lowering mean inbreeding coefficients and/or increasing heterozygosity of SNPs or haplotypes.
Outbreeding programs are akin to a species survival plan (SSP) that is utilized when attempting to "rescue" an endangered species. The vast majority of dog and cat breeds do not show evidence of genetic depletion such as low reproductive success and increased stillborn and neonatal mortality.
Recommendations to outbreed (only breed to those least related) homogenizes breeds and erases the genetic difference between individuals. It is a self-limiting process that requires matings be done between individuals who are genetically different from each other. Eventually, there will be no more "lines" with differences. Everyone will be in the center and no one at the periphery.
By erasing the genetic difference between individuals, this averts selective pressure for improvement. Breed gene pool diversity requires distinct lines in order to create selective pressure. A mix of breeding individuals from different lines within the breed maintains allelic polymorphism.
Breeders strive to select for healthy conformational, behavioral, and working standards for their breeds. Selection over time allows more individuals to conform to a standard.
Attempts to create heterozygosity for SNPs and haplotypes that have no defined positive or negative gene effect have as much a chance of reversing selection-based improvements as they have for being beneficial to a breed's genetic health.
This has been shown in cattle breeds: Prioritization based on neutral genetic diversity may fail to conserve important characteristics in cattle breeds (Hall et al. J Anim Breed Genet. 2012;129(3):218–225).
Prudent breeding practices allow some linebreeding, some outbreeding, and even occasional inbreeding, with different breeders maintaining breeding lines or crossing lines as they see fit. It is the different opinion and breeding actions of breeders that maintain breed diversity.
We see increased genetic disease in purebred and crossbred animals due to a lack of genetic testing and selection of breeding animals, and an associated increase in disease liability genes. 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.
Genetic homozygosity is a function of speciation and breed formation. It is only detrimental if related to disease liability genes or impaired health. We must ensure that our selection recommendations improve breeds and do not impede breeder efforts for progress in breed health, conformation, and function.