A single gene makes some poodles purse-sized while allowing a Great Dane to look a pony in the eye, US scientists reported on Thursday in a finding that may shed light on human size differences and diseases.
Dogs vary dramatically in size, more so than any other mammal. The key to those differences appears to lie in a variant of the IGF1 growth gene, the researchers reported in this week's issue of the journal Science.
"We found that IGF1 is a master regulator for determining body size in domestic dogs," said Nathan Sutter of the National Human Genome Research Institute, one of the National Institutes of Health, who helped lead the study.
All small dogs in the study shared a short bit of DNA that reduced the output of the IGF1 gene, the team of 21 researchers found. Medium-sized and large dogs did not.
The discovery is important because IGF1 -- insulin-like growth factor 1 -- is found in all dogs and other species, including humans.
"For many genes that we look at in the human, there is a counterpart gene in the dog," Sutter said.
By learning how genes control body size in dogs, the researchers believe they can gain an understanding about skeletal size in humans. It may also lead to a greater knowledge of the role genes play in diseases like cancer, in which the ability of regulate cell growth is lost.
If we can build a vocabulary for body size determination in the dog, we are setting ourselves along the road toward understanding complex diseases not only in the dog, but also in the human," Sutter said.
Domestic dogs have come a long way since they branched off from the gray wolf more than 15,000 years ago. Years of selective breeding have produced giants like the mastiff, which can exceed 200 pounds (91 kg), all the way down to the Chihuahua, weighing in at no more than 6 pounds (2.7 kg).
Love that dog
The research got its start through a pet named Georgie, a Portuguese water dog owned by University of Utah researcher K Gordon Lark, one of the study's co-authors.
When Georgie died of an autoimmune disorder, Lark sought out a replacement and discovered the breed was ideal for a genetic study because it has a wide diversity of size but very few founders.
Lark and others began "The Georgie Project," looking for DNA that made the breed range in size from 25 to 75 pounds (11 to 35 kg).
He and Utah colleague Kevin Chase enlisted DNA samples and body size measurements from more than 500 Portuguese water dogs. They suspected IGF1 because it produces a growth factor.
Using those findings, Sutter and his colleagues isolated a stretch of DNA, home to the IGF1 gene, which also strongly correlated with size in the breed.
"The IGF1 gene is an amazing gene. It pops up all over the place. Differences in this gene's sequence account for different risks in a person getting prostate cancer," Sutter said.
To confirm the link to size, researchers at NIH expanded the study to include 526 dogs from 14 small breeds, ranging from Chihuahua, Pomeranian, Yorkshire terrier and Japanese chin, to nine giant breeds such as the mastiff, Saint Bernard and Irish wolfhound.
Ultimately, they looked at DNA in more than 3,000 dogs from 143 breeds.
"The same gene variant is present in each of the small dog breeds," Sutter said.