Start of funding 01.01.2009

Large-scale resequencing of 500 nuclear-encoded mitochondrial genes in patients with mitochondrial disorders and Parkinson's disease

Dr. med. Tobias Haack
Ludwig-Maximilians-University of Munich
Neurologische Klinik und Poliklinik im Klinikum München - Großhadern

Prof. Dr. Ronald W. Davis
Stanford University
Stanford Genome Technology Center - Dept. of Biochemistry



Nuclear genes encode the majority of the proteins involved in mitochondrial function and biogenesis and their mutations cause diverse and debilitating clinical disorders. About half of the estimated 1.500 nuclear-encoded mitochondrial proteins have been catalogued in the Mitochondria database MitoP2. However, no feasible systematic tool exists to date to study hundreds of those genes in hundreds of patients. Here, I propose a systematic approach to analyze the DNA sequence of 500 mitochondrial genes in 300 patients with Parkinson’s disease and 200 patients with mitochondrial disorders of unknown aetiology. This project will take advantage of new DNA sequencing technologies developed at the Stanford Genome Technology Center (SGTC). The systematic correlation of newly identified DNA variations and clinical phenotype information will allow the study of genotype-phenotype associations in Parkinson’s disease. Once established, this new approach can then be expanded to study other mitochondrial neurodegenerative diseases.