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Genetic Origin of Short Legs in Dogs

A single genetic event (a DNA insertion) is responsible for the origin of short, curved legs in dachshunds, corgis, basset hounds, and at least 16 other breeds of dogs. Researchers from the National Human Genome Research Institute, and collaborators, reported this finding online in Science on July 16. Specifically, the researchers found that, in contrast to other dog breeds, all short-legged dog breeds have an extra copy of the gene that codes for a growth-promoting protein called fibroblast growth factor 4 (FGF4). Although functional, the extra gene lacks certain parts of the DNA code, called introns, found in normal genes. These characteristics led researchers to conclude that the extra gene is a so-called “retrogene” that was inserted into the dog genome some time after the ancestor of modern dog breeds diverged from wolves. In the case of short-legged dogs, the inserted retrogene results in the overproduction of the FGF4 protein, which researchers hypothesized might turn on key growth receptors at the wrong times during fetal development. Veterinary researchers already know that in certain dog breeds the development of long bones is curtailed due to calcification of growth plates, resulting in short legs with a curved appearance. The trait, called disproportional dwarfism, or chondrodysplasia, is an American Kennel Club standard for more than a dozen domestic dog breeds, including the dachshund, corgi, Pekingese, and basset hound. This trait is distinct from the uniformly miniature size of toy breeds, such as the toy poodle. "Our findings suggest that retrogenes may play a larger role in evolution than has been previously thought, especially as a source of diversity within species," said the study's first author, Dr. Heidi Parker. "We were surprised to find that just one retrogene inserted at one point during the evolution of a species could yield such a dramatic physical trait that has been conserved over time." The findings also may have implications for understanding human biology and disease. Researchers noted that some people are affected by a similar appearing growth disorder, called hypochondroplasia, which belongs to a group of conditions commonly referred to as dwarfism. While about two-thirds of cases of human hypochondroplasia have been linked to a different gene, the cause of the other one-third remains a mystery. "This study points to a new gene that should be investigated for its possible role in human hypochondroplasia," said Dr. Elaine Ostrander, the study's senior author. "Our findings may prove valuable to scientists studying other aspects of human growth and development. The work also underscores the value of canine studies for uncovering new biological mechanisms that are likely relevant to human disease." [Press release] [Science abstract]