Duke U. researchers discover genetic link to Parkinson's October 11, 2000 By Matt Brumm - The Chronicle Duke U. (U-WIRE) DURHAM, N.C. -- Combing through mounds of genetic data collected from more than 100 families nationwide, Medical Center researchers recently became the first to discover a genetic mutation associated with late-onset Parkinson's disease. Parkinson's is a degenerative neurological disorder that leads to the gradual loss of muscle control. A separate mutation in the same gene -- named Parkin by the Japanese scientists who discovered it -- had already been known to be affiliated with the less common early-onset form of the disease, but Duke scientists established that the gene also could be responsible for Parkinson's in older patients. "We have evidence for the first particular mutation that seems to be associated with later age of onset (of Parkinson's disease)," said Jeffery Vance, associate professor of neurology. Vance and his colleagues studied more than 800 individuals from 174 families from across the United States, looking for areas of variation in the human genome that appeared to be passed on faithfully in families with a history of Parkinson's disease. They noticed that the Parkin gene contained the most solid marker of the areas they studied. Upon further analysis, the researchers found a common but previously unknown deletion of 40 DNA base-pairs that prevents a protein from being manufactured correctly. "No one has found this particular deletion, and it's found in families from all over the U.S.," Vance said. "It's very common in our population; we don't know why." Vance emphasized that the population examined by the Duke team was much more diverse than those looked at previously by the Japanese and other scientists exploring Parkinson's disease. Margaret Pericak-Vance, professor of medical genetics and director of the Center for Human Genetics, said gene linkages such as this one show that instead of being caused entirely by environmental factors, Parkinson's also has a genetic basis. "The susceptibility gene interacts with environmental (causes); it's not an independent thing," Pericak-Vance said. "It's clear that the genome plays a significant role." Although the exact function of the protein coded by the Parkin gene is not yet known, researchers think it may function in protein destruction. Vance said the Parkin protein has elements that are very similar to a protein called ubiquitin, which he described as being similar to "an angel of death" for the other proteins it encounters. Cells use ubiquitin to mark proteins scheduled to be eliminated; once ubiquitin is attached, other proteins recognize this indicator and disassemble the targeted molecule. William Scott, an assistant research professor of medical genetics who worked on the project, said Parkin may attach ubiquitin to proteins so they can be degraded in the cell. "It has long been thought that Parkinson's disease is caused at least in part by problems in the ubiquitin pathway," Scott said. Pericak-Vance likened this latest breakthrough to "another piece of the orange peeled" in the effort to understand the complex genetic and physiological interactions related to the disorder. While investigators may still be far from illuminating the darkest mysteries of Parkinson's disease, they can still speculate on how research such as this could be beneficial for pharmaceutical development. "If you can figure out the important proteins involved in complex diseases, then that will either give you a target for a drug, or, more likely, put you in the biological pathway and tell you what are important targets for drugs," Vance said. (C) 2000 The Chronicle via U-WIRE Copyright © 2000 At Home Corporation. All rights reserved. -- Judith Richards, London, Ontario, Canada [log in to unmask] Today’s Research... Tomorrow’s Cure