From Nature:
A single gene may explain the vast size difference between that tiny terrier yapping in the park and the massive mastiff ignoring the din. Nate Sutter, a geneticist at the National Human Genome Research Institute in Bethesda, Maryland, wanted to know the reason why big dogs, such as Irish wolfhounds, can grow up to 50 times larger than other members of their own species, such as chihuahuas. So he started out looking at large and small dogs of one breed — the Portuguese water dog.
Scientists on the team took X-rays of 500 Portuguese water dogs and made 91 measurements of their skeletons. Based on these data, the researchers classified the water dogs as either big or small for their own breed. They then looked for differences in DNA between the large and small water dogs. This is a relatively easy job: a consortium of scientists including Sutter published the DNA sequence of the dog genome last December, and have mapped out the places where there is a lot of variation between individuals in a given breed. There are fewer of these places of variation in purebred dogs than there are in humans.
The team found that one of the few differences in these Portuguese water dogs occurred in a gene called ‘insulin-like growth factor 1’, or Igf-1.
More here.