Mapping the locus of autosomal dominant polycystic kidney disease: diagnostic application.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common autosomal dominant disorders affecting humans. The recent identification of a number of restriction fragment length polymorphisms linked to ADPKD now offers a method for diagnosis in families that are large enough for linkage and phase of linkage to be established. Initial studies of greater than 50 families with the disease localized all disease-producing mutations to the short arm of chromosome 16. Recently, however, families have been identified in which linkage to 16p markers cannot be detected. Such genetic heterogeneity of linkage limits the value of diagnostic methods based on linkage analysis and focuses attention on the need for direct diagnosis of disease-producing mutations. This in turn requires the isolation, cloning, and characterization of ADPKD genes. A refined map of the region around the PKD1 gene, the ADPKD gene localized on chromosome 16p, is presented.