Vienna (19th July 2011) A team of researchers at the University Department of Neurology of the Medical University of Vienna has succeeded in identifying a gene that is mutated in individuals with Parkinson’s disease. The research team leader Alexander Zimprich said: „We have taken here a meaningful step forward in Parkinson’s disease research“.
The newly discovered gene is known as VPS35, the sixth one which has been associated with Parkinson’s disease and the third dominant gene. “VPS35 is one of the three genes which cause late-onset Parkinson’s, at an age of about 60 years“, explains Zimprich. Another dominant Parkinson’s gene had already been discovered by Zimprich’s team at the MedUni Vienna in 2004: the LRRk2 gene. This dominant gene causes a form of Parkinson’s disease similar to “sporadic“ Parkinson’s.
30 million DNA components were analysed
The origin of the present research effort was an Austrian family with seven affected members who had been under the care of the Neurology Clinic at the Linz General Hospital for many years. All protein-coding DNA regions from two affected family members were completely sequenced, aided by a sequencing technology which has only become available recently. This process is called “Next Generation“ parallel sequencing. Using this new technology, the scientists were able to analyse more than 30 million DNA components in just a few days. Such a comprehensive analysis of the whole genome in such a short time would have been unthinkable just a few years ago. More than 20,000 variants of the gene were found in every one of the patients. After numerous filtration processes and various exclusion steps, there was finally only one mutation in the VPS35 gene which could be responsible for the disease in the members of this family (VPS35-Asp620Asn). The researchers estimate the proportion of all cases of Parkinson’s disease caused by this gene to be 1.0 percent. Indeed, Zimprich is of the opinion that we can "analyse the metabolic pathways of Parkinson’s at the molecular level better" because of this discovery. This would be of great value to researchers of this disease.
Other institutes in Austria and the Helmholtz Centre for Genetics in Germany also participated in this study under the direction of Asst. Prof. Dr. Alexander Zimprich.
Does VPS35 also play a role in Alzheimer’s?
A certain cargo protein (SORL1) in particular aroused the interest of the research group: Certain genetic variations of this same protein were found a few years ago in increased numbers in Alzheimer’s patients. “To what extent there is a possible connection in the etiology of the two most common neurodegenerative diseases is a fascinating question, but one which cannot yet be answered“, said Zimprich. Publication in the “American Journal of Human Genetics“
Incidentally, a Canadian research group succeeded at the same time in identifying the same mutation in a large Swiss family. Both studies can be read in the current issue of “American Journal of Human Genetics“, the professional journal of the American Society of Human Genetics.
Facts about Parkinson’s disease
Parkinson’s disease is, after Alzheimer’s dementia, worldwide the second most common neurodegenerative disease. About one percent of people over the age of 60 is affected. In Austria alone, the number of people with Parkinson’s disease is estimated to be about 20,000. Certain cell groups in the brain which produce the neurotransmitter dopamine die in this disease. This results in typical symptoms such as general hypokinesia and a characteristic tremor. It is assumed that one out of ten people affected possesses a strong genetic disposition for the disease. Zimprich: “Families with several affected members present a rare and important opportunity to identify these dispositions“.