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Gene Makes Small Dogs Small

Small breeds share a gene variant that limits their growth
big dog and small dog



© DEANNE FITZMAURICE
In big news for small dogs everywhere, researchers have found a tie that binds the small breeds, from Chihuahua to Pomeranian to Pekingese: they all share the same version of a gene for a growth hormone called insulin-like growth factor 1 (IGF1). A group gathered DNA samples from thousands of dogs representing more than 100 breeds, looking for common genetic denominators amongst the great variety of shapes and sizes. Small breeds, it turns out, all have a piece of DNA that seems to repress the IGF1 gene and hence stunts their growth, researchers report.

Dogs vary in size more than any other land animal and come in 155 breeds in the U.S. alone, according to the American Kennel Club. The new finding, however, suggests that relatively few genes may separate dogs as different as tiny toy poodles and massive Saint Bernards, says geneticist Elaine Ostrander of the National Human Genome Research Institute, who led the new study. "When you look at their appearance you're struck by the amazing amount of variation," she says. "You just expected it to be a more complicated story."

A team at the University of Utah had been analyzing small genetic differences in Portuguese water dogs, a breed that ranges in size from 25 to 75 pounds. The researchers observed that the smaller members of the breed had an identical piece of DNA near the IGF1 gene on dog chromosome 15. The IGF1 protein is crucial for the growth of mammals, including mice and humans, so Ostrander's group and other collaborators began collecting DNA from additional breeds to see if they also shared the same gene variant.

The researchers took doggy cheek swabs and blood samples at dog shows, dog parks and contests for obedience and agility—anywhere pooches could be found, Ostrander says. They eventually obtained samples from 3,241 dogs of 143 breeds, ranging in size from the two-kilogram (4-pound) Chihuahua to the 82-kilogram (180-pound) mastiff.

Using a series of genetic landmarks, Nathan Sutter, a researcher in Ostrander's laboratory (and the owner of a chocolate lab named "Maddie") homed in on a short region near IGF1 that comes in more than a dozen slightly different forms.

"We found one very specific signature in all the dogs from small breeds," Ostrander says. Among 549 dogs from 14 breeds that average less than nine kilograms (20 pounds), 510 carried the same form of IGF1, the group reports in this week's Science. Of dogs heavier than 31 kilograms (68 pounds), fewer than 10 percent possessed the same variant; instead, most of them had one of two other variants.

"To us that was really amazing," Ostranders says, "because it was telling us this gene is really a master regulator." The small breed variant probably represses IGF1 and other genes that cause larger breeds to grow, she says, adding that smaller dogs have less IGF1 in their blood.

That does not mean that breeders could create a 200-pound Chihuahua by swapping the small IGF1 variant for another, she says, because multiple genes work together to shape a breed's traits, including its size. Some smaller dogs have IGF1 variants found in larger breeds and vice versa, the researchers report. Rottweilers, for example, carry the small breed variant.

It makes sense that only a few genes would suffice to determine a trait such as body size, Ostrander says, because all dog breeds belong to the same species, Canis familiaris, and most have taken shape in the last three centuries.

Ostrander says that by identifying other dog genes for body size and for traits such as leg length and head shape, researchers may learn more about growth and its disorders—especially cancer—in humans and their best friends. People with certain forms of IGF1 are more susceptible to prostate cancer, she notes. "We don't know all the things it does yet."

The researchers say that because some of the breeds they studied are relatively unrelated, IGF1 has probably played a role in dog size for a long time. The domestic dog descended from the gray wolf at least 15,000 years ago. Teams have uncovered 14,000- to 15,000-year-old remains of Great Dane–like dogs from eastern Russia. Remains from the Middle East and Europe, dating back 10,000- to 12,000 years, resemble small terriers, suggesting to the researchers that a primitive version of the small-breed variant existed back then.

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