DNA testing and domestic dogs - Cathryn Mellersh

The domestic dog, inherited disease, and DNA testing

Excerpt...

"Intense selection, high levels of inbreeding, the extensive use of a limited number of sires, and genetic isolation are all hallmarks of modern breeds of domestic dog. It is widely agreed that part of the collateral damage from these practices is that purebred dogs have a greater risk of suffering from genetically simple inherited disorders than their cross-breed cousins. Intense media interest continues to apply pressure on both dog breeders and the veterinary profession to improve the health of purebred dogs, the result being that these stakeholders are turning increasingly to DNA tests to assist with both breeding decisions and also the diagnostic process. Some dog breeders are exceptionally well informed when it comes to genetics and possess a very good understanding of the inherited disorders that affect their breed(s). But many are not, and they rely on their general practice veterinarian for information, who also may not have a good knowledge of the majority of inherited conditions that affect all the different breeds they encounter.

It is, therefore, ultimately the responsibility of the scientists who identify genetic variants associated with canine inherited disorders to exercise prudence when they make DNA tests available. Purebred dog populations, by definition, are genetically compromised, with many having an unequivocal need to maximise diversity. Breeders are increasingly using DNA tests to shape their breeding decisions, with the need to reduce the frequency of deleterious mutations being balanced with the need to maintain genetic diversity. There is a critical need, therefore, for full and transparent information, written in lay terms, explaining (1) the mode of inheritance and penetrance of specific mutations, (2) the risk of disease associated with specific genotypes, (3) the frequency of each mutation within different breed populations, and (4) the breeds that are genuinely at risk, so that dogs are not unnecessarily eliminated from the breeding population. The existence of phenocopies within the breed, if known, should also be documented.

DNA testing of companion animals is unregulated, and so one of the few ways in which potential “customers” can judge the merit of any DNA test is if a description of the mutation on which the test is based has been accepted by a peer-reviewed scientific publication. However, the data that establish a genetic variant as a provocative candidate for downstream, comparative studies (and therefore worthy of publication) is not always the same information that a dog owner needs to discern whether they should use the DNA test and what decisions to make in light of the results. It is therefore not sufficient for a DNA test provider merely to provide a hyperlink to a peer-reviewed publication without backing it up with some layman-friendly explanation.

It is worth noting that once a mutation has been reported in the scientific literature there is little stopping private, for-profit organisations from offering a genetic test based on a published finding, irrespective of the opinion of the scientists who made the discovery. Therefore, suggesting that researchers have absolute control over which DNA tests are offered might be an oversimplification in some cases. Nevertheless, scientists should certainly be encouraged to offer “user-friendly” advice on how to use genetic tests and to work with dog breed clubs and organisations to disseminate this advice. Perhaps they should also be willing to suggest when consideration of a particular disease-associated variant to shape breeding decisions is inappropriate."

Summary

"Genetic tools available with which to dissect the canine genome are becoming increasingly sophisticated, and the number of disease-associated genetic variants that will be identified over the next few years will undoubtedly increase dramatically. These mutations will form the basis of extremely valuable tools that dog owners and breeders will clamour to use to eliminate both Mendelian and complex inherited conditions from their beloved breeds. If the public is to maintain confidence in these new tools, scientists must be responsible custodians of their findings, and make DNA tests commercially available only if they can be accompanied by straightforward, transparent, user-friendly advice on how they should be used to reduce the frequency of disease without reducing genetic diversity unnecessarily."