FEATURE ARTICLE
Genetics and the Shape of Dogs
Studying the new sequence of the canine genome shows how tiny genetic changes can create enormous variation within a single species
Elaine A. Ostrander
A Faster Dog
Studies such as those described above are well designed for understanding complex or multigenic traits. But there remains some "low-hanging fruit" to be harvested in the study of canine morphology—other cases where apparently single genes contribute to major traits of interest. An example is provided by my research group's study of the whippet and a mutation in the gene coding for myostatin, a growth factor that limits the buildup of muscle tissue. In this study we found a new mutation in the myostatin gene, MSTN, and observed that it results in a double-muscled phenotype known as the "bully" whippet.
The typical whippet, a medium-sized sight hound, is similar in appearance to dogs of the greyhound breed and weighs about nine kilograms. Whippets are characterized by a slim build, long neck, small head and pointed snout. Bully whippets, however, have broad chests and an unusually well-developed leg and neck musculature that makes them unattractive to fanciers of the breed.
Using a candidate gene approach, we showed that individuals with the bully phenotype carry two copies of a two-base-pair deletion in the third exon (a gene region that is transcribed to make portions of proteins) of MSTN, with the result that a truncated or mutant protein is produced. These findings were somewhat expected, as the double-muscle phenotype observed in the whippet is reminiscent of what has been reported in mice, cattle and sheep and in a single case in humans, each of which was caused by a mutation in the myostatin gene. The specifics for dogs, however, were useful to the whippet dog community, which is seeking to develop a genetic test that will reduce the number of dogs produced with the bully phenotype.
Interestingly, we also found that individuals carrying only one copy of the mutation are, on average, more muscular than wild-type individuals, as measured by their neck and chest girth as well as mass-to-height ratio. Indeed, we estimated that mutations in myostatin explain approximately 60 percent of the variation in both the ratio of height to weight and neck girth, and 31 percent of the variation in chest size. In addition to the statistically significant differences between dogs that were bully and wild types, dogs who carried one copy of the variant allele were more heavily muscled then their wild-type counterparts, although not nearly as heavily muscled as the bully dogs.
This observation caused us to ask whether dogs that carried one copy of the mutation were faster racers—a success that would likely lead them to be bred more, which in turn could produce bully dogs if two recessive-gene individuals were paired. Careful analysis revealed an association between individuals carrying one copy of the MSTN mutation and racing speed. Dogs that were the faster racers (class A) were more likely to carry the mutation then were dogs that were slower racers (classes B, C and D). Least likely to carry the mutation were dogs that had never raced and were primarily show dogs.
We considered the possibility that the result could be explained solely by the fact that A racers tended to be mated more often to A racers as opposed to B, C, D or nonracing dogs. This tendency would predict a significant amount of population substructure among A racing dogs. Although we demonstrated that some population substructure exists, we were able to show that it did not fully account for the observation that an excess of A racing dogs carried the myostatin mutation compared to dogs that either did not race or were class B, C or D. Indeed, 50 percent of the A racers tested carried the mutation. We did not find the variant in greyhounds or any of the heavily muscled mastiff breeds such as the bulldog.
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