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Human Genome News, January 1998; 9:(1-2)
For the first time, scientists have identified a gene abnormality that causes some cases of Parkinson's disease. The finding, reported in Science [276, 2045-47 (June 27, 1997)], confirms a previous report that a predisposition to at least one form of Parkinson's is inherited and that a gene on the long arm of chromosome 4 is involved. Researchers have now implicated a single base-pair mutation in this alpha synuclein gene, which plays a role in the function of nerve cells.
Parkinson's disease afflicts about 500,000 people in the United States, initially causing shaking or trembling limbs, and in later stages a slow, shuffling walk and stooped posture. It results from loss of nerve cells in a brain region that controls movement, thus creating a shortage of the brain-signaling chemical dopamine. The recent finding gives researchers a powerful new tool for understanding cellular abnormalities in Parkinson's and demonstrates a connection with research into other neurological disorders such as Alzheimer's disease.
Using information generated by the Human Genome Project, researchers rapidly located the mutation in a region containing about 100 genes, including the alpha synuclein gene. This gene was an excellent candidate for Parkinson's involvement because its potential role in neurodegenerative diseases already had been demonstrated when fragments of alpha synuclein protein were found in the characteristic amyloid plaques in the brains of Alzheimer's patients. Researchers hypothesize that the alpha synuclein protein mutation causes it to aggregate, thus attracting other proteins to form a deposit that damages cells. A common mechanism may be operating in both these neurodegenerative diseases.
Researchers suspect that the abnormal gene is responsible for a significant portion of familial Parkinson's disease with onset generally before age 60. Scientists are searching for mutations in other synuclein genes among Parkinson's patients who do not have the alpha synuclein mutation.
The paper's senior author, Robert Nussbaum (NHGRI), cautioned that, "For people with Parkinson's disease, this is a small but important step in a very long journey. . . . It is important to stress that at this point there is no direct therapeutic result from this finding." A test based on this gene abnormality would provide limited information for most people. In high-risk families, one application for such a test would be to facilitate research into possible stabilizing or preventive measures.
Discovery of the mutant alpha synuclein genes raises genetic-testing issues similar to those for such other late-onset diseases as Alzheimer's disease and Huntington's disease. Notes Francis Collins (NHGRI), "As more gene sites are identified, it will become almost routine for disease-gene hunters to find an already characterized gene waiting for them when they arrive at the neighborhood they know is involved in a disease. But this discovery, which raises the possibility of identifying healthy individuals at future risk for illness, also underlines again how crucial it is to provide legislative protections against misuse of the information, especially in health insurance and employment."
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Human Genome Program, U.S. Department of Energy, Human Genome News (v9n1).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.