The identification of new genetic causes of Parkinson's disease

Parkinson disease (PD) is a common neurological disorder affecting about 1% of the population aged 60 or older. The disorder is causing high costs to society and reduced quality of life in patients and caregivers. Like many other neurological illnesses, P D is chronic, progressive and only symptomatic treatment is available. There is a present urge to increase the biological understanding of the disease process to provide the rationale for disease prevention and new therapies. A major breakthrough in rece nt years has been the cloning of genes causing monogenic forms of PD. Indeed, much of our present knowledge about the pathogenesis of the disorder has come from the study of these genetic forms. The complexity of many complex diseases might be primarily d ue to genetic heterogeneity, with defects of different genes causing the same disease. There is growing evidence that rare alleles play a major role in the etiology of complex disorders, and that a large proportion of single-gene defects causing disease h ave not yet been identified. The principal aim of the project is to identify new genetic causes of PD. The studies will be performed using novel gene sequencing technologies combined with advanced bioinformatics analyses. Samples from patients with famil ial or early-onset disease will be selected for whole exome sequencing to identify new genes causing PD. Candidate genes will be examined in a large series of patients to confirm pathogenicity, and subsequent genotype-phenotype studies will be performed. All samples for the study originates from the Norwegian population, a population characterized by the presence of founder mutations, which is greatly increasing the power to identify new disease genes. The successful identification of new genes predis posing to PD would be of great importance for understanding the molecular basis of the disease, and will establish new routes to diagnosis and therapeutic advances of great medical benefit.