To ascertain a large cohort of affected relative pairs with clinically defined Parkinson's disease.
To perform a genome wide search for genes responsible for susceptibility to Parkinson' s disease.
Parkinson's disease (PD) is a progressive neurodegenerative disorder which is a common cause of disability, affecting more than one per cent of the population aged 55 or over. Despite intensive research efforts over several decades, the cause of PD has not been established, and treatment confers only temporary benefit. In neurodegenerative disorders caused by single gene defects, but otherwise of unknown aetiology, much progress has been made in increasing our understanding of disease mechanisms by isolating the gene concerned. There is increasing and compelling evidence for a genetic component to the aetiology of PD. The objective of the proposed project is to map and identify genes which concern genetic susceptibility to PD, with the aim of defining the aetiology and pathophysiology of this common and disabling disorder and, ultimately, devising new means of prevention and therapy. The project is based on similar principles to a successful research effort which recently identified susceptibility genes in type 1 diabetes mellitus. Possible susceptibility loci will be detected by analysis of genetic linkage data, derived from genotyping about 400 highly informative DNA polymorphisms, evenly distributed over the whole genome, in a large cohort of 150 affected sib pairs with PD and their relatives. Putative susceptibility genes will be identified more precisely by further genetic mapping, allelic association studies, and candidate gene analyses. Ascertainment of, and collection of DNA samples from, the 300 families will be undertaken jointly by five clinical partners in five EU countries using rigorous diagnostic criteria. Such an extensive network is needed to obtain the requisite number of families. The genomic search will be shared by four laboratories and the resulting genotype data analysed centrally. The project will generate more than half a million genotypes, and the work could not be done in a single laboratory in a short time without major resource implications for staff, equipment and laboratory space. The project will benefit scientifically and economically from the combined clinical and scientific expertise of the partners. Progress will be monitored closely by the project steering group in order to ensure that project milestones are achieved. The identification of susceptibility genes for PD should throw light on the pathogenesis of this disease of high socio-economic importance, lead to the design of effective therapies and preventive measures, and will be useful in giving genetic advice to patients and their families.
Funding SchemeCSC - Cost-sharing contracts
3000 DR Rotterdam