Parkinson's genetics: molecular insights for the new millennium

In idiopathic Parkinson's disease and familial parkinsonism, the limited number of overlapping clinical and pathological outcomes argue that a common underlying molecular pathway is perturbed. Genetic methods are a powerful approach to identify molecular components of disease. We summarize recent attempts to identify the genetic components of familial parkinsonism, without a priori assumptions about disease causation. Much effort has been expended on mapping in families with early-onset disease, in which parkinsonism appears inherited as a Mendelian trait. More recently, association methods have been employed in late-onset disease using affected sib-pairs and population isolates. These findings have been extrapolated to Parkinson's disease in the community with some success. We review the molecular synthesis now emerging from a genetic perspective.