Scientists track down the gene that turns Great Dane into a chihuahua

[cezene]

A gene that makes small dogs small, explaining the difference in size between breeds such as the St Bernard and the chihuahua, has been discovered by scientists. Their research could also point to a genetic influence on human height.
Variations in a section of DNA that controls production of a critical growth hormone appear to determine whether dogs will develop the fearsome proportions of a mastiff or the dainty, toy-like dimensions of a pekinese.

Almost all the small dogs examined for the genetic study, including chihuahuas, toy terriers and pomeranians, share a mutated sequence of DNA that lies close to the gene for insulin-like growth factor, 1 (IGF-1).

This protein is known to play an important role in bone and muscle development and in ultimate body size, and the section of DNA next door to it, known as a regulatory sequence, appears to limit production at critical points of a dog’s growth.

Large breeds such as Irish wolfhounds, Great Danes and St Bernards, by contrast, do not have the same regulatory sequence next to the IGF-1 gene, removing restrictions to their growth.

The findings, which are published in the journal Science, offer a surprisingly simple explanation for the remarkable variation in size among dogs.

Because of intense selective breeding since the animals were first domesticated from wolves about 15,000 years ago, the species boasts the widest variation in body size of any mammal.

While scientists have always known that these differences must be explained by genes, they did not expect to find that the same sequence of DNA seems to be universally responsible for a small body size.

“All dogs under 20lb have this. All of them,” said Gordon Lark, of the University of Utah, one of the leaders of the study. “That’s extraordinary.”

It is not known, however, whether the genetic mutation also influences other behaviours typical of small dogs. “Yappy, we didn’t study,” said Kevin Chase, his colleague at Utah.

There is one strange anomaly in the findings: rottweilers also have the small-dog mutation, and the researchers believe that they must have other gene variants to make them so big.

The IGF-1 gene is also thought to influence growth patterns in other mammals, including human beings. A similar regulatory sequence could explain differences in human stature, as well as offering insights into diseases in which IGF-1 can be involved, such as cancer.

Elaine Ostrander, scientific director of the US National Human Genome Research Institute, said: “By learning how genes control body size in dogs, we are apt to learn something about how skeletal body size is genetically programmed in humans. We also will increase our data set of genes likely to play a role in diseases such as cancer, in which regulation of cell growth has been lost.”

The research team began investigating the genes that influence dog size by studying Portuguese water dogs, the breed that shows the greatest variation in size. Dr Lark said: “By studying the Portuguese water dog, which has threefold range of sizes — from 25lb to 75lb — we realized that IGF-1 was a big player.”

Dr Lark was drawn to study dog genetics, and Portuguese water dogs in particular, by chance. In 1986, when he was working on soya bean genetics, he adopted a stray dog he named Georgie, which he later discovered was a Portuguese water dog. In 1996, when Georgie died, he contacted Karen Miller, a breeder in New York State, to buy a replacement. On hearing that he studied genetics, Ms Miller suggested he look at dog genetics and gave him an expensive Portuguese water dog, Mopsa, as well as 5,000 pedigrees.

The researchers said that the selective breeding of small dogs was probably the result of human attraction to small, cute things.

Dr Chase, who owns two 4lb toy poodle-maltese mixes, said: “Everybody treats their dogs like their babies, so it’s not surprising they would select tiny dogs. Tiny dogs are not particularly functional. They don’t hunt with you. They don’t protect your house. They don’t pull carts. They’re just small and sweet.”