Identification of Recessive Genes Causative for Parkinson’s Disease using Exome Sequencing

Parkinson disease (PD) is a progressive degenerative disorder of the central nervous system, representing the second most common neurologic disorders of the elderly. It is characterized by the loss of dopaminergic neurons. The loss of these neurons is associated with the typical tremor at rest; other symptoms include muscle rigidity, a slowing of physical movement, and, often, anxiety-depression symptoms. PD is a complex disorder generally caused by the interaction between many environmental and genetic factors. In the rare genetic forms, the disease is due to mutations in a single gene and it is inherited in the family. Not all genes involved in these rare genetic forms have been identified. In this project, we want to discover new genes that cause PD in an autosomic recessive manner. Our research is based on a new technology that allow the sequencing in a single individual of the full exome, that is the part of the genome that coded for proteins. The exome will be fully sequenced in subjects with a probable genetic autosomal recessive PD: patients derived from families with one or more sibling affected and consanguineous parents will be analyzed. The presence of a strong familiarity (siblings affected) and the consanguinity enhance the probability of a recessive genetic form. The new candidate genes identified will be analyzed in a large series of patients and controls to confirm their involvement in PD pathogenesis. Hopefully, this project will allow the further elucidation of molecular mechanisms underlying the onset and progression of PD, and the elaboration of new strategies of prevention and therapy.