Newly identified gene mutation linked to Parkinson's: Single 'spelling mistake' affects mechanism for converting a cell's genetic code into proteins

The mutation, a single "spelling mistake" among three billion nucleotides in DNA, regulates the mechanism for converting a cell's genetic code into proteins. The findings is being published in The American Journal of Human Genetics.

The mutation, EIF4G1, was found in a family from northern France that has a high rate of the disease -- more than half of the members of each generation develop it.

The lead scientist on the study, Matthew Farrer, a professor in the Dept. of Medical Genetics and Canada Excellence Research Chair in Neurogenetics and Translational Neuroscience at UBC, says that when the location of the mutation was discovered and he determined which gene it affected, "it didn't make a lot of sense at first."

"Translating a gene into a protein is such a fundamental process to the life of a cell," says Farrer, who also was named the Dr. Donald Rix B.C. Leadership Chair in Genetic Medicine last week. "I thought it would be unlikely to lead to this form of Parkinson's, which appears later in an individual's life, and affects only a small subset of brain cells."

But Farrer, a member of the Brain Research Centre at UBC and Vancouver Coastal Health Research Institute, realized that this particular protein translation is important only when the cell is confronted by some kind of stress -- for example, a lack of oxygen or nutrients.

Moreover, the protein specifically regulates the cell's ability to recycle its own components. That provides a crucial link to Parkinson's disease, because a hallmark of Parkinson's is the presence of "Lewy bodies" -- collections of discarded proteins that remain trapped in certain brain cells.

More than 100,000 Canadians, approximately one million Americans and more than 10 million people worldwide are affected by Parkinson's disease. Symptoms include trembling in hands, arms, legs, and face, stiffness in the limbs and torso, as well as slow movement and poor balance and coordination. There is currently no cure and most treatments only tackle the symptoms.

"This discovery provides direct evidence that Parkinson's may result from gene-environmental interactions," Farrer says. "The resulting impairment highlights neuronal recycling systems as a focal point in the effort to develop more effective drugs."

The genetic samples were obtained through a collaboration with researchers the Université Lille Nord de France that began in 1998. Much of the laboratory work was conducted while Farrer worked at the Mayo Clinic in Jacksonville, Florida.

The majority of support for the research came from the French government and the U.S. National Institutes of Health.