HUMAN ADENOSINE A(1) RECEPTOR GENE - SYSTEMATIC SCREENING FOR DNA-SEQUENCE VARIATION AND LINKAGE MAPPING ON CHROMOSOME 1Q31-32.1 USING A SILENT POLYMORPHISM IN THE CODING REGION

Adenosine is a major inhibitory neuromodulator in the central nervous system. One of the receptors mediating the central effects of adenosin e is the adenosine A(1) receptor. We performed a systematic mutation s can of the coding region of the adenosine A(1) receptor gene to explor e its variability in the general population investigating 40 unrelated healthy subjects by single-strand conformation analysis no sequence c hanges of likely functional relevance were observed. We detected, howe ver, a frequent T to G substitution at nucleotide position 716 which c onstitutes the first variant described in an adenosine receptor gene. It was used for fine scale linkage mapping of the A(1) gene. Employing a polymerase-chain-reaction based restriction assay, we genotyped 7 C EPH families (Centre d'Etude du Polymorphisme Humaine) and mapped the receptor in a gene cluster around the renin gene on chromosome lq31-32 .1 In addition, we utilized the 716T/G polymorphism to demonstrate bia llelic expression of the adenosine A(1) receptor gene in adult human b rain. (C) 1995 Academic Press, Inc.