James F. Gusella
The Molecular Neurogenetics Unit consists of a group of investigators dedicated to the exploration of inherited disorders of the nervous system and more recently of other systems using primarily a molecular biological approach. In any given disorder, the research can usually be divided into three sequential stages: 1. Determination of the chromosomal location of the gene defect based on family studies with polymorphic genetic markers; 2) Isolation of the disease gene based on its chromosomal location using a variety of genome analysis strategies and 3) Analysis of the normal and defective versions of the culprit gene in man, and in appropriate in vitro or in vivo model systems. The approaches in the latter case include among others creation of transgenic mouse models, analysis of existing animal models, expression of gene products in cultured cells and genetic analysis in Drosophila and other model organisms. Currently active are research projects aimed at Alzheimer disease, Huntington's disease, neurofibromatosis 1, neurofibromatosis 2, Parkinson's disease, multiple sclerosis, familial dysautonomia, torsion dystonia, tuberous sclerosis, the neuronal ceroid lipofuscinoses, the periodic paralyses, Down syndrome, familial spastic paraperesis, hypospadias, and tumors of the nervous system and the periphery. The Unit also has a concentrated program of human genome mapping aimed at applying new technologies to particular chromosomal regions for rapid gene identification, and a program of development of viral vector systems for reintroducing genes into the nervous system. The latter also offers promise as a method of gene therapy aimed at killing nervous system tumors. The ultimate goal of our approach is to define the precise steps by which any given genetic defect leads to the characteristic pathogenesis of a disorder, thereby acquiring the knowledge needed to develop rational therapies for correcting the disorder.