Holistic Management of Genetic Traits
Tufts' Canine and Feline Breeding and Genetics Conference, 2013
Anita Oberbauer, PhD
Department of Animal Science, University of California, Davis, CA, USA

In breeding any species, first and foremost there should be goals and objectives. Breeders have different goals (improve the breed, optimize performance characteristics, win, financial remuneration), and some may view their goals as being more noble than the goals of others. Regardless, in any breeding endeavor, one must strive for that specific goal(s) and in doing so make concessions. The hallmarks of a successful breeder include making progress toward the overall objective while minimizing the negative impact of tradeoffs.

Above, several possible breeding objectives were listed. An animal in a breeding pool is a composite of numerous elements that include desired type, health, performance, reproductive efficiency, structure, and temperament. When selecting breeding animals, these elements must be prioritized and their relative importance to one another weighed. For example, a dog or cat that is ideal in every category but lacks fertility fails to reach a breeding objective. A highly fertile dog or cat that lacks desired type likewise fails to meet a breeding goal. Thus, in any breeding program, one must achieve a balance blending often conflicting aspects.

Unfortunately, rather than looking at the long view and complexities of achieving breeding goals, the majority of claims against concerted breeding programs (purebred dog or cat, for example) center on a perceived lack of concern by breeders to reduce harmful genetic conditions in order to win, make money, satisfy ego, or (fill in the blank). Yet when breeders and owners are asked to define "health" in relationship to dogs (or cats), definitions are many and varied. Definitions can be pragmatic (not needing visits to the veterinarian), focused solely on physical health, or focused solely on mental health; most commonly cited attributes of "health" are absence of disease or injury concomitant with the ability to perform normal/expected body functions and abilities. Most breeders or owners focus on the individual when considering health. In contrast, livestock producers also include population health (so-called "herd health") as a significant component of their concept of "health." Herd health is especially critical for large numbers of animals and/or densely populated animal groupings. Stepping back and considering health in a broader perspective, herd health is definitely applicable to the dog population as a whole or to a particular breed. One can consider genetic health of the population as underpinning all the elements a breeder needs to attain a breeding goal.

An individual's qualities (health, temperament, type, etc.) are a reflection of the population's genetic potential. When selecting an individual for breeding, the breeder should balance the individual's needs (a certain dog may need a mate who has a better shoulder assembly) with that of the population as a whole (excessive use of a popular sire can reduce the genetic diversity for future generations). Further, the breeder must make compromises. Even if the absolute perfect breed specimen is produced, to perpetuate that individual, one must breed to a mate that has faults. What qualities should be emphasized in the less-than-perfect mate? One breeder will say type (and that includes every attribute ranging from eye color, muzzle shape, ear placement, length of back, to bend of stifle and beyond!), whereas a second breeder will insist that temperament is most critical (and temperament also has a spectrum of qualifiers). Yet a third breeder will insist upon health (as discussed above, health means different things to different people). Despite the varied opinions, each breeder should have a prioritized and weighted view to a breeding program. Even then, the suite of traits that comprises the general element (type, performance, etc.) in each needs to be prioritized and weighted. While no breeder would knowingly breed genetic defects, should one trade less-than-ideal eye color for better eye shape?

The domestication of the dog and cat reflected selection on traits that favored successful cohabitation with the human population. The inherent genetic diversity of the ancestral wolf permitted the expression of many traits that favored domestication. Yet the domestication process reduced some genetic diversity that was present in its ancestor; that is, bottlenecks in which limited numbers of individuals established a relationship with humans created subpopulations. Genetic diversity is critical to compensate for current and future challenges. For example, the restricted genetic diversity in the endangered black-tailed prairie dog has resulted in their susceptibility to an exotic, introduced pathogen that causes plague. Maintaining genetic diversity maintains the health of the population. Thus, the founding dog population represented a subset of the ancestral wolf, and therefore dogs began with a smaller gene pool. The establishment of breeds within the dog population as a whole further reduced the gene pools for each breed.

The challenge in breeding is to fix the desirable traits while maintaining genetic diversity. Loss of genetic variety within a unique population (read "breed") is considered highly detrimental to the overall genetic health of a breed. A population may begin with a limited gene pool. Developing a new breed and then closing the registry for that breed equates to a small gene pool. Using inbreeding schemes to fix desirable traits reduces genetic diversity by increasing the genetic homozygosity, that is, making both copies of a gene identical. Increased homozygosity ensures that a particular desirable trait will be expressed; it also potentiates the expression of genetic disorders that are recessively inherited. Furthermore, loss of heterozygosity is statistically correlated with greater autoimmune concerns. Taken together, although inbreeding enhances uniformity within litters and fixes characteristic, breed-defining traits, it also has unintended consequences such as loss of rare alleles, increased homozygosity enabling expression of recessive disorders, and reducing effective population size. Thus, inbreeding has been the subject of much debate concerning the welfare and health of purebred dogs.

Similarly, extensive use of a popular sire also reduces heterozygosity, effectively reducing the population size. The use of a popular sire also proves to be more effective at dispersing deleterious alleles within a breed than inbreeding (Leroy, Baumung 2010), making disorders that occur in a popular sire (or one for which he carries the mutant alleles) more difficult to manage in the future. In humans, the mutation rate resulting in random errors in DNA is one mutation in every 100 million base pairs equaling ~ 60 new mutations per generation, and more mutations arise from the male (Conrad et al. 2011). Each human is estimated to carry approximately 1,000 deleterious mutations (Sunyaev et al. 2001). Also in humans, it has been demonstrated (Chun, Fay 2011) that natural selection to eliminate some deleterious alleles may increase the frequency of others; a deleterious allele may hitchhike along with a desirable allele due to genetic linkage. In one review, all top 50 breeds that the study evaluated had at least one genetic disorder associated with the conformation demanded by the standard (Asher et al. 2009). Deleterious mutations are difficult to eliminate from small populations and are likely to accumulate.

The association of deleterious with desirable traits has implications for proponents mandating only individuals clear of deleterious alleles be permitted to breed. When considering genetic health of an individual in relation to the population health, no single individual is free from all genetic mutation. A dog - any dog - when all genetic diseases have been characterized will fail at least one genetic test. Limiting breeding to those clear will further restrict the gene pool and introduce unintended health consequences. That does not mean that genetic testing is unwarranted. As Dr. Jerry Bell states, "breeding without genetic testing is irresponsible, and unethical." Using available test results in a holistic approach is key to maintaining the overall genetic health of a breed.

In some cases the genetic test may indicate a risk, but not guarantee, of expression of a disease (for example, degenerative myelopathy - Chang et al. 2013). Utilizing that information to inform breeding decisions is critical, but eliminating all dogs having a risk from the breeding population is unwise. In other cases, the presence of an allele may be viewed as deleterious or an asset. A particular allele for a behavioral trait is associated with highly productive working dogs, although owners should emphasize nonconfrontational training methods to achieve optimal performance; yet there is significant association between spontaneous episodic aggressive behaviors in dogs with that allele (Lit et al. 2013). Maintaining that diversity within the gene pool permits breeders to attain their individual goals.

A comment on crowd sourcing of health information: popular beliefs can be very wrong even if commonly held. An example from history: It was universally believed that the world was flat; even though there was consensus, it did not make that view factual. Just because "everyone" says it's true does not make it so, and sensible caution should be applied to health statements. Much is made of "healthy" mixed breeds; domesticated dogs carry deleterious mutations dating back to the original domestication step. Thus, there are health conditions that will be present in a dog, any dog - be it a purebred or mixed-breed dog.

Concerted breeding to reduce unwanted traits is the only means to eliminate particular conditions. Wisdom and stewardship of a breed are essential. The genetic health of a breed depends upon wise sire and dam selection.

References

1.  Asher L, Diesel G, Summers JF, McGreevy PD, Collins LM. Inherited defects in pedigree dogs. Part 1: disorders related to breed standards. Vet J. 2009;182:402–411.

2.  Calboli FCF, Sampson J, Fretwell N, Balding DJ. Population structure and inbreeding from pedigree analysis of purebred dogs. Genetics. 2008;179:593–601.

3.  Chang HS, Kamishina H, Mizukami K, Momoi Y, Katayama M, Rahman MM, Uddin MM, Yabuki A, Kohyama M, Yamato O. Genotyping assays for the canine degenerative myelopathy-associated c.118G>A (p.E40K) mutation of the SOD1 gene using conventional and real-time PCR methods: a high prevalence in the Pembroke Welsh corgi breed in Japan. J Vet Med Sci. 2013;75:795–798.

4.  Chun S, Fay JC. Evidence for hitchhiking of deleterious mutations within the human genome. PLoS Genet. 2011;7(8):e1002240. www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002240

5.  Conrad, et al. For the 1000 Genomes Project. Variation in genome-wide mutation rates within and between human families. Nat Genet. 2011;43:712–714.

6.  Leroy G, Baumung R. Mating practices and the dissemination of genetic disorders in domestic animals, based on the example of dog breeding. Anim Genet. 2011;42(1):66–74. doi 10.1111/j.1365-2052.2010.02079.x.

7.  Lit L, Belanger JM, Boehm D, Lybarger N, Haverbeke A, Diederich C, Oberbauer AM. Characterization of a dopamine transporter polymorphism and behavior in Belgian Malinois. BMC Genet. 2013;14:45. www.biomedcentral.com/1471-2156/14/45

8.  Sunyaev S, Ramensky V, Koch I, Lathe W, Kondrashov A, et al. Prediction of deleterious human alleles. Hum Mol Genet. 2001;10:591–597.

9.  OMIA (Online Medelian Inheritance in Animals). Reprogen. Faculty of Veterinary Science, University of Sydney. December 2010. http://omia.angis.org.au

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Anita Oberbauer, PhD
Department of Animal Science
University of California
Davis, CA, USA


MAIN : Lectures : Holistic Management
Powered By VIN
SAID=27