We have a senior systems architect, programmer/bioinformatician, statistician and three geneticists on staff that work closely with the molecular genetic laboratory core. Our strength is molecular and statistical genetic problems in neurologic disorders, including classical linkage and association approaches as well as more contemporary methods for next-generation sequence manipulation and analysis. We employ case-control, family and island population mapping methods to identify susceptibility variants underlying disease. Through collaborative partnerships, the success of these endeavors has led to a number of novel gene mutation discoveries, and high profile publications, which have helped to focus neuroscience investigation and translational research.
One example is implicating alpha-synuclein in Parkinson’s disease. Our group was one of the first to show common variability influences susceptibility to idiopathic Parkinson’s disease in many populations. We have also identified missense and multiplication mutations that segregate with familial parkinsonism. We first showed SNCA duplications and triplications lead to a 50% and 100% increase in mRNA and protein expression in the brain; the greater the expression, the earlier the onset of motor and cognitive symptoms, and the faster disease progression. We subsequently went on to develop RNA interference as a therapeutic strategy to lower endogenous alpha-synuclein expression.