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Deconstructing the Gene Pool

MN: The herding breeds, whose origins were in Great Britain, all shared the mutation, indicating that they had common ancestors. This implies that these types of dogs were mixing, presumably before registries were established. If the mutation was shared by these breeds, there probably are many other genes also shared. Great Britain in the 1800s appears to have been a real melting pot for dog genes, and this has been substantiated by subsequent work in our laboratory.

JB: Why is it important to know the history of a genetic mutation?

MN: Because the information may tell us something about the distribution of the mutated gene, and key us into where we might look to find additional affected breeds. For instance, if this particular mutation had been ancient, we would have predicted that many more breeds would have had it. Given all the breeds that exist worldwide, and that only a small fraction of these were affected by the mutation, we can infer that the mutation is relatively young. The mutation probably arose in the mid-1800s, but this is speculative. Reconstructing history, genetic or otherwise, always involves an incomplete data set—you never know what’s been lost.

JB: Should breeders genetically test their breeding stock, and if so, how should they apply the test results?

MN: Breeders have it hard—when they make decisions, they have to consider what’s good for the breed, their bloodline and individual dogs. If the mutation frequency is high in the breed, like it is with Collies and Long-haired Whippets, testing and selective breeding is certainly worthwhile to reduce the frequency and decrease the breed’s risk of drug sensitivity. In a breed where the mutation is relatively rare, such as the Old English Sheepdog, the owner might test only those dogs that are scheduled for treatment with one of the interacting drugs. But it gets complicated when a single breeder’s bloodline is heavily affected; breeders cannot give up their entire breeding stock, so a more gradual approach must be taken. What a breeder should do really depends on the specific situation.

I certainly believe that eliminating mutations from gene pools requires greater debate. Many scientists have suggested that a mutation should be removed from a gene pool gradually so as to preserve genetic diversity in the breed. I think ulterior motives are sometimes at work, as this is most strenuously advocated by service laboratories that offer these kinds of tests. DNA tests should be targeted for obsolescence—ultimately, a mutation should be eliminated from the gene pool, which of course renders the test meaningless. Don’t get me wrong—there is enormous value in preserving genetic diversity across breeds, but most of the diversity in one breed exists in related breeds, so conservation genetics within a breed is not a critical issue. I’m certain that far more genetic diversity is lost from “popular sire” effects and line breeding than from adherence to DNA testing.

JB: When I think of conservation genetics, I think of bringing a species back from the brink of collapse, or more generally, the practice of making a species healthy again. Do you mean that preserving genetic diversity in dog breeds is not critical because the way you create a breed in the first place is by eliminating diversity?

MN:
That’s right. The normal rules of conservation genetics don’t apply to artificially selected populations. For instance, there appears to be an advantage in nature for individuals to have a lot of genetic variation in at least one region of the genome—the MHC—that arms the body’s self-defense. It appears that individuals may actually select mates in part based on being genetically different for genes at the MHC. In dogs, we have obliterated this selection because dogs don’t get to choose their mates.

There is an enormous difference between a species that breeds and evolves naturally and one whose breeding and evolution are controlled by humans. The irrefutable fact of closing a gene pool by enlisting dogs to a closed registry to suspend change in a breed is that diversity is being lost, and there’s little or no opportunity to create new diversity. Mutations are incredibly rare, at least those that have effect, and there isn’t any new blood coming into these populations.

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