Identification of Parkinson’s disease and essential tremor genes by next-generation sequencing and haplotype analysis

Parkinson’s disease (PD) and essential tremor (ET) are frequent invalidating neurological disorders with familial aggregation in 30% and 70% of cases, respectively, that share both phenotypic and etiological factors. Although several genes with disease-causing mutations have been identified in familial PD and ET, the etiology of most cases remains uknown. Next generation sequencing is a powerful tool in order to identify novel pathogenic variants, as previously described in Alzheimer’s disease. Through whole-exome sequencing (WES), we performed an exhaustive genetic analysis in PD and ET families in which the affected individuals did not have mutations in the most frequent genes. Among all the obtained variants, 15 variants meeting the selection criteria were confirmed by direct sequencing. Our aim is to study the frequency of these variants in a large cohort of cases (n=1000) and healthy controls (n=1000) by using high-throughput sequencing platforms to confirm their association with these diseases. With this project we want to discover novel genes involved in PD and ET as well as to obtain new diagnostic markers that will allow to classify phenotypically these disorders and to design future gene-based therapies.