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Short dogs and dwarfism

Certain breeds of dogs may have developed distinctively short legs following a single change to the genetic code during their evolution, according to a finding that may also help explain a type of human dwarfism.

Researchers with the National Human Genome Research Institute (NHGRI) found that about 20 short-legged dog breeds, including dachshunds, corgis and basset hounds, have two copies of a gene that play a role in production of the protein fibroblast growth factor 4 (FGF4). The copies are not identical, though, as one lacks some essential parts of the DNA code, according to the study published July 16 in the online edition of Science.

"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," study first author Heidi G. Parker, of NHGRI, said in a news release from the U.S. National Institutes of Health. "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."

Retrogenes occur when a transcription error in the creation of DNA code causes a functional, but imperfect duplicate of a gene to be inserted into the code. A type of virus, called a retrovirus, often causes the error to occur. The team theorizes that this one-time mutation may have occurred early in the breeds' transformation from wild to domesticated animals.

The retrogene in the short-legged dogs produces too much of the FGF4 growth protein, which the team believes may cause growth receptors to be switched on at the wrong time during foetal development. This may be behind the known calcification of growth plates that prevents these breeds' legs from growing, a condition known as disproportional dwarfism, or chondrodysplasia, that is distinctive to these breeds.

Humans can have a similar condition called hypochondroplasia, one of several conditions generally referred to as dwarfism. Researchers have linked two-thirds of the human cases to a different gene, but the cause of the remaining third is unknown.

"This study points to a new gene that should be investigated for its possible role in human hypochondroplasia," study author Elaine Ostrander, a senior investigator in NHGRIs Division of Intramural Research, said in the same news release. "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." - (HealthDay News, July 2009)

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