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Researchers find gene that determines dog size
« on: April 11, 2007, 05:44:44 AM »
Researchers find gene that determines dog size
Canines' regulatory DNA could have human corollary

Thomas H. Maugh II, Los Angeles Times
Friday, April 6, 2007

Researchers have finally solved one of the great canine mysteries: Why are small dogs small?

As it turns out, small dogs all bear a tiny piece of regulatory DNA that shuts off the gene that produces a powerful growth factor.

The gene regulator was probably inherited from a miniature wolf about 15,000 years ago a -- though it has since disappeared from the wolf population -- and has spread rapidly throughout the dog world by human intervention.

"All dogs under 20 pounds have this -- all of them," said biologist K. Gordon Lark of the University of Utah, one of the authors of the paper published today in the journal Science. "That's extraordinary."

The discovery helps explain the great diversity in size among dog breeds, the greatest diversity among any mammalian species. It also may have implications for humans.

"By learning how genes control body size in dogs, we are apt to learn something about how skeletal size is genetically programmed in humans," said geneticist Elaine Ostrander of the National Human Genome Research Institute, who led the study.

The gene in question, IGF-1, is the blueprint for a protein called insulinlike growth factor, which not only plays a role in human growth but also is implicated in cancer and certain skeletal diseases.

Learning how it is controlled will have many applications in humans, said Jeff Sossamon of the American Kennel Club's Canine Health Foundation, who was not involved in the research. "The canine model is perfect for human research, because we share 85 percent of our genetic makeup with dogs," he said. "And we share 300 common diseases."

The study was triggered by Lark, who began studying the genetics of soybeans. Along the way, he adopted a stray dog called Georgie, who turned out to be a Portuguese water dog. When Georgie died in 1996, Lark contacted Karen Miller, a breeder in New York state, for a replacement.

When she found out Lark studied genetics, she began pestering him to study dog genetics and sent him an expensive Portuguese water dog -- Mopsa, who is now 10 years old. Within three months, she also sent him 5,000 pedigrees -- the genetic histories of individual dogs.

Lark and his colleague, biologist Kevin Chase, soon realized that the Portuguese water dogs were ideal for genetic studies because they all descended from a small number of "founders." They also are permitted an unusually large range of sizes for a purebred dog, ranging from 25 to 75 pounds.

Lark and Chase began collecting X-rays -- to document body size -- and DNA samples from owners of other Portuguese water dogs, eventually accumulating more than 500 samples. They initially concluded that a segment of chromosome 15 containing IGF-1 and about 100 other genes was strongly correlated with size in the animals.

They focused on IGF-1 because a defective form of the gene previously had been associated with small mice and an unusual case of a tiny person. The gene itself was fine, but they found genetic changes in a regulatory sequence sitting next to it.

The study was then expanded to look at other dogs. Ostrander and colleagues traveled to dog shows around the United States, collecting DNA samples from various breeds.

Eventually, they accumulated and analyzed genetic samples from 3,241 dogs from 143 breeds. All the small dogs had the same altered regulatory sequence.

So, too, did the occasional big dog, such as a Rottweiler and a mastiff.

"There is something funny going on with Rottweilers," Ostrander said. "That told us right away that that the whole story isn't IGF-1. There are other genes that interact, and we are going after them right now."

The team also is looking for the genes that control leg length and width.

Because the regulatory variant is found in small dogs that are only distantly related and in widely dispersed locales, the team concluded that the variant must have originated about the time wolves were domesticated by humans.

Lark speculated that small dogs arose because "a small wolf couldn't survive in nature, but it could survive in company with humans," or because an early human "wanted to domesticate a wolf and they didn't want to adopt a big sucker."


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Re: Researchers find gene that determines dog size
« Reply #1 on: April 11, 2007, 12:39:28 PM »

The Canine Spectrum

by Beth Novey

Danka Kordak Slovakia, a long-haired Chihuahua, was the world's smallest dog until his death in September 2006. He was 5.4 inches tall. AFP/Getty Images, April 5, 2007 Danka Kordak Slovakia, a long-haired Chihuahua from Revuca, Slovakia, held the record of world's smallest dog until his death in September 2006. Danka was 5.4 inches tall and 7.4 inches long. Weighing just 27 ounces, he ate 2.5 ounces of dog food a day. Since his death, no one has put forth a paw to claim the title of world's smallest dog.

While Danka was the tiniest dog in terms of height, Heaven Sent Brandy, a female Chihuahua from Florida, currently holds the record lengthwise; she is 6 inches from her nose to the tip of her tail. She is not allowed on her owner's couch, for fear that she will injure herself jumping off.

On the other end of the spectrum, the tallest living dog is Gibson, a harlequin Great Dane, who is 43 inches tall. He weighs in at 170 pounds and is over 7 feet tall when standing on his hind legs. Gibson has been measured against several professional basketball players. He lives with his owner, Sandy Hall, in Grass Valley, Calif.

Gibson, a harlequin Great Dane, is currently the tallest dog in the world. When standing on his hind legs, he is over 7 feet tall.  Courtesy of Sandy Hall

Though the Guinness Book of World Records does not currently list the world's heaviest dog, as of 2001, the heaviest living dog was a 284-pound English mastiff named Hercules. According to his owner, he eats a pound of dry dog food each day.

On average, small dogs (8 inches and under) tend to live longer than large dogs (24 inches and up). Small dogs usually live 12 to 15 years, while large dogs have a life expectancy of eight to 10 years.

Sources: The Guinness Book of World Records; CNN; St. Petersburg Times; Paul Jones; and Sandy Hall.


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Re: Researchers find gene that determines dog size
« Reply #2 on: April 11, 2007, 12:42:01 PM »
You don't find people the size of insects or giraffes; humans are all roughly the same size. The same is true of most species. There isn't a huge difference between the biggest and the smallest.

One exception to the rule may be lying at your feet right now: the dog. There are very, very big dogs and teeny, tiny dogs.

Modern dogs are the offspring of the offspring of the offspring of gray wolves the ancestry goes back thousands of years. But while there are many kinds of wolves, they're all approximately the same size. So why are dogs different?

Scientists have been taking canine cheek swabs to find out. Their report appears this week in the journal Science.

Nathan Sutter is a geneticist at the National Institutes of Health. He says the largest dog ever seen was an Irish wolfhound named Merlin.

"[He] won at Westminster," Sutter says. "He's enormous. He's the size of a horse."

Sutter says the smallest dog ever might have been a Chihuahua named Frenchie, just two pounds as an adult. Merlin is some 80 times heavier than little Frenchie.

To find out how the dog genome generates such large and small animals, Sutter and other researchers studied the Portuguese water dog.

Elaine Ostrander runs the genetics lab at NIH that performed some of the analysis.

"[Portuguese water dogs] were actually used by the fisherman to send messages between boats," Ostrander says. "They would herd the fish into nets. They could retrieve fish or articles from the water. They were also used to guard the fishing boats, and they could be used to help bring in the nets."

Portuguese water dogs come in both big and small sizes. Today, most dogs bred for competition have to fall into narrow size ranges, but the rules for Portuguese water dogs happen to be looser.

The researchers analyzed Portuguese water dog DNA and found a single gene what Ostrander calls a master regulator that seems to account for a big part of the size difference. Small Portuguese water dogs had one version, while larger Portuguese water dogs had different versions.

But was this just the case with the Portuguese water dog?

For two years, the researchers went to dog shows and anywhere they could find dogs to collect dog DNA. They took blood samples from Chihuahuas, Pekingese, Mastiffs, Great Danes many blood samples and cheek swabs.

Were dogs happy to offer a cheek swab?

"They didn't care," Ostrander says, "especially if they were going to get a treat or if there was a tennis ball in our other hand."

The results came in. And just as with the Portuguese water dogs, the small breeds had one variant of the gene, while big dogs had different variants.

Ostrander says it is surprising that a single gene plays such a prominent role in all dogs.

"When you look at the different dog breeds," Ostrander says, "and you look at their histories, and they've come from all over world, and they've been bred to do such different things it just seemed to us that the story had to be more complex."

But it wasn't more complex. So you have to wonder, why and when did these variants evolve? You can see why big dogs might thrive, but what evolutionary force made it beneficial to be tiny?

One possibility is that humans were the evolutionary force. There is no evidence that wolves had the genetic variant for small size. It is possible that when humans started to domesticate dogs, a bit of DNA didn't get copied right, and a small dog appeared in a litter.

We kept it, protected it, bred it. Maybe we thought it was cute, or more likely, useful.

"We really, really don't know," says Paul Jones from the Waltham Pet Center, in England, who worked on the project.

"It was just a very, very lucky event," Jones says. "And it's probably lucky for man as well. When you think about humans, when they actually first started farming barley, wheat and everything, they actually started gathering those food stores together. As you know, you need to protect those food stores from mice and rats and the ideal dog to do that is a small, terrier-like dog."

Jones hopes study of dog genomes may lead to healthier pets. Dog may be man's best friend, but there's this sad truth: Humans can live 80 years, but dogs, barely 15.


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Re: Researchers find gene that determines dog size
« Reply #3 on: April 11, 2007, 02:24:20 PM »