Genomic organization and mapping of the human and mouse neuronal beta 2-nicotinic acetylcholine receptor genes

As a first step in determining whether there are polymorphisms in the nicot inic acetylcholine receptor (nAChR) genes that are associated with nicotine addiction, we isolated genomic clones of the beta 2-nAChR genes from human and mouse BAC libraries. Although cDNA sequences were available for the hu man gene, only the promoter sequence had been reported for the mouse gene. We determined the genomic structures by sequencing 12 kb of the human gene and over 7 kb of the mouse gene. While the sizes of exons in the mouse and human genes are the same, the introns differ in size. Both promoters have a high CC content (60-80%) proximal to the AUG and share a neural-restrictiv e silencer element (NRSE), but overall sequence identity is only 72%. Using a 6-Mb YAC contig of Chr 1, we mapped the human beta 2-nAChR gene, CHRNB2, to 1q21.3 with the order of markers cen, FLG, IVL, LORI CHRNB2, tel. The m ouse gene, Acrb2, had previously been mapped to Chr 3 in a region orthologo us to human Chr 1. We refined mapping of the mouse gene and other markers o n a radiation hybrid panel of Chr 3 and found the order cen, Acrb2, Lor, Iv 1, Flg, tel. Our results indicate that this cluster of markers on human Chr 1 is inverted with respect to its orientation on the chromosome compared w ith markers in the orthologous region of mouse Chr 3.