Identification of Mutation in a Rat Model for Human Parkinson’s Disease

Parkinson''s disease is a progressive disorder of the nervous system that affects walking, movement and coordination. This disease is diagnosed in more than 50,000 Americans each year. Recently, we have identified a rat model which shows early onset of a motor neuron defect phenotype similar to that in Parkinson’s patients. The goal of the project is to identify, through next generation sequencing , the underlying mutation of this rat model for human Parkinson’s disease. Whole genome sequencing will be performed for a set of distantly related rats with conditions mimicking human Parkinson’s disease. Litter mates of the mutant rats without phenotype will also be sequenced as controls. Based on the recessive inheritance model, candidate homozygous variants shared by the mutant rat while either absent or heterozygous in the control rat will be further tested in additional rats to confirm its segregation with the phenotype. Due to the lack of good Parkinson’s animal models, establishing and further characterizing this new rat model will shed important insights on this important human disease.