Huntington's disease (HD) is a progressive, neurodegenerative, autosomal dominant disease which generally manifests itself in the third to fifth decades of life. The goal of this project is to develop a genetic linkage test for the presymptomatic and prenatal diagnosis of Huntington's disease. In Phase I we will develop the capability for conducting a field trial in Phase II for the testing of individuals at-risk for Huntington's disease by genetic linkage analysis. The technical feasibility of identifying particular genotypes associated with HD-linked polymorphic DNA markers will be reliably and accurately determined during Phase I. Procedures for sample collection, storage, DNA extraction, and hybridization will be optimized and a pilot reference laboratory for haplotyping with HD-linked markers will be established. Critical elements associated with the administration of a genetic linkage test for Huntington's disease will be identified and procedures and mechanisms for addressing these issues will be developed.