GENETIC-MAPPING OF ADRENERGIC-RECEPTOR GENES IN HUMANS

We have genetically mapped the genes encoding four human adrenergic re ceptors (ARs) of subtypes alpha(1)C, alpha(2)A, alpha(2) beta, and bet a(1), which are prototypic G protein coupled receptors that mediate th e physiological effects of neurotransmitters, hormones, and drugs. We placed these genes onto the Cooperative Human Linkage Center (CHLC) an d Genethon framework maps, within confidence intervals with greater th an 1000:1 odds. With multipoint analysis the alpha(1)C gene (locus ADR A1C) mapped to the interval between NEFL and D8S283; alpha(2)C4, the g ene encoding the alpha(2)C AR (locus ADRA2C), mapped to the interval b etween D4S126 and D4S62; and the alpha(2)-C10 (alpha(2)A AR)/beta(1) h aplotype (loci ADRA2A/ADRB1) mapped to the interval between D10S259 an d D10S187. A fifth AR gene, beta(2), yielded significant LOD scores wi th markers on the long arm of chromosome 5; however, this locus (ADRB2 ) could not be mapped to any specific interval with odds of greater th an 1000:1. The two AR genes that are completely linked, alpha(2)-C10 a nd beta(1), were oriented on their shared 225-kb genomic fragment rela tive to the direction of transcription, with beta(1) being 5' to alpha (2)-C10. The positioning of these genes on high-density framework maps allows them to be tested as candidates in a spectrum of diseases that might involve AR dysfunction.