By Kevin E. Noonan ---
Single nucleotide polymorphisms (SNPs) have been detected since the beginning of the third revolution in genetics characterized by cloning, sequencing, and the various organismal genome projects (rediscovery of Mendel's laws being the first and Watson and Crick's elucidation of the structure of DNA being the second). SNPs were first associated with restriction length fragment polymorphisms, a technique developed for chromosomal gene mapping (particularly for disease genes) and disease trait genealogy in the days before the entire human genome had been sequenced. One well-known use of the technique was Mary Clare King's identification of Central American death squad victims from their remains found in mass graves, and the existence of SNPs has been predicted to be the key to the new world of personalized medicine.
One of the more interesting SNPs, and one having global consequences, was reported in Science last week. Nathan Sutter and his colleagues at the National Human Genome Research Institute (a part of the National Institutes of Health) and several other university and corporate research centers reported that a SNP in the insulin-like growth factor 1 gene (IGF-1) in dogs is responsible for the vast differences in size between different breeds. Using both traditional genetic tools and the products of the dog genome project, these workers found an SNP shared by all "miniature" dog breeds and absent from all larger breeds. The group's work was facilitated by the great range in size between breeds (the largest among terrestrial vertebrates), the well-established delineation of breeds and maintenance of breed standards by international dog breeding societies, and the completion of the dog genome project. The genetic results were supported by biochemical studies showing lower IGF-1 levels in blood serum from small dogs than large dogs.
Since all domestic dogs are descendants of the common grey wolf found throughout Eurasia, the existence of this trait is the consequence of at least 15,000 years of human selective breeding (although the great majority of dog breeds have been developed over the past few hundred years). It is readily apparent why this trait was selected for during domestication, producing breeds that are smaller than the wolf, and thus less of a threat to man, as well as improving characteristics of domesticated breeds such as reduced food (and water) requirements. The persistence of the mutation in the almost 15,000 years between initial domestication and active human selection for miniature dog breeds suggests that the variant gene containing the SNP is important for inter alia maintaining the tendency for dog breeds smaller than the size of the original grey wolf stock.
Interestingly, until the publication of these results, there was no consensus on the genetic causes of the great diversity in breed size, with researchers positing such variables as increased mutation or recombination rates, distribution of short repeat sequences in the dog genome, differences in regulatory genes, and readily-altered developmental programming.
The implications for human development are unclear, but suggest that human size variation may also be influenced by such polymorphisms. Dissection of SNP variant frequency in humans or other mammalian species at IGF-1 can be expected in view of the Sutter team's results.
Sutter et al., 2007, Science 316(5821): 112-115 (April 6, 2007)
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