PRECISE MAPPING OF THE BRAIN ALPHA(2)-ADRENERGIC RECEPTOR GENE WITHINCHROMOSOME 4P16

The gene encoding the brain alpha(2)-adrenergic receptor (ADRA2C) is l ocated on human chromosome 4. It has been circumstantially associated with a number of human disorders, including Parkinson disease, panic d isorders, and Huntington disease (HD). Using somatic cell hybrids, we localized the gene to chromosome 4p16 distal to P8 (D4S62). To investi gate this locus further, we isolated several cosmid clones covering th e entire gene. The gene was found to be intronless. Two (GT), repeats in close proximity to the ADRAC2 gene were analyzed and used to define its precise location. Linkage disequilibrium studies of one microsate llite in KD families showed strong nonrandom association to the HD mut ation, indicating its tight linkage to the KD gene. The investigation of families carrying recombinant chromosomes, pulsed-field analysis, a nd genomic walking mapped the ADRABC gene adjacent to D4S81, 500 kb pr oximal to the HD gene. The newly defined microsatellites at the ADRAC2 locus, its precise localization within 4p16, and the detailed PCR con ditions facilitate the identification of any defect caused by this gen e. (C) 1994 Academic Press, Inc.