Location cloning strategy for characterizing genetic defects in Huntington's disease and Alzheimer's disease.

The recognition that DNA polymorphisms are widespread in the human genome and can be used as high quality genetic markers has introduced a new strategy for approaching inherited disorders for which no protein defect has been identified. Genetic linkage analysis can establish the chromosomal position of the genetic defect, providing a potential opportunity for isolating the disease gene and characterizing its product in the absence of any knowledge of its biochemical function. The first step in this location cloning approach has been successful in mapping the Huntington's disease gene to chromosome 4, and has implicated chromosome 21 as the site of a defect in familial Alzheimer's disease. An intensive effort is under way to narrow the region containing the disease gene and identify the defect in each of these disorders. This review will present the success that has been achieved and the problems that remain and will assess the current status of the location cloning strategy with regard to Huntington's disease and familial Alzheimer's disease.