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
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