Scientists have found a second genetic link to Parkinson's disease (PD). The discovery, described in the March Nature Genetics, strengthens the theory that genes play a role in the neurodegenerative disease and may help researchers track down the causes behind the disorder, which afflicts between 500,000 and 1 million people in the United States alone.
For many years, researchers had debated whether genes could be blamed for Parkinson's, as most patients have no obvious family history of the disease. But last June, a team identified the first gene that seems to cause a familial form of PD (Science, 27 June 1997, p. 1973). That gene's influence turned out to be limited: Not all afflicted families carry defects in the gene, and it has yet to be linked to any of the much larger number of "sporadic" cases, so called because they don't seem to have a hereditary component. In addition, the disease caused by the mutation is unusual in that it begins at an especially early age.
In contrast, Thomas Gasser of the University of Munich and Bertram Müller-Myhsok of the Bernhard-Nocht Institute for Tropical Medicine in Hamburg and their colleagues have studied families in the United States, Canada, and Europe whose affected members resemble typical sporadic cases. Using computer programs to search the genomes of family members for genetic markers that are more common in disease sufferers than in their unaffected relatives, the researchers located a region on chromosome 2 that seems to be linked to the disease.
The team has not yet fingered a specific gene among the 100 or so present in the suspect region, but at least one candidate, Gasser says, "would almost seem too good to be true." It codes for a protein called transforming growth factor-a (TGF-a), which has been shown in cell cultures to promote growth of dopaminergic neurons--the cells that are damaged in PD. A shortage of TGF-a, the researchers speculate, might leave the neurons vulnerable to damage by environmental factors that might also contribute to the disease. Gasser says he and his colleagues are testing their patients for mutations in the TGF-a gene.
The researchers caution that their link may turn out to be as limited as the first one, but Michael Polymeropoulos of the National Human Genome Research Institute in Bethesda, Maryland, a member of the team that found the first gene, says the new work is "spectacular" and will help scientists figure out what goes wrong in brain cells to cause the disease.