The signal-transducing G proteins are heterotrimers composed of three subunits, α, β, and γ. Multiple distinctive forms of the α, β, and γ subunits, each encoded by a distinct gene, have been described. To investigate further the structural diversity of the β subunits, we recently cloned and characterized a novel cDNA encoding a third form of the G protein β subunit, which we have termed β3. The protein corresponding to β3 has not yet been identified. The three forms of the β subunit show 81-90% amino acid sequence identity. Previous studies had localized the human genes for the β1 and β2 subunits to chromosomes 1 and 7, respectively. The present studies were designed to determine whether the gene encoding β3 is linked to either the β1 or the β2 gene. Genomic DNA was isolated from a panel of rodent-human hybrid cell lines and analyzed by hybridization to cDNAs for β1 and β3. Discordancy analysis allowed assignment of the β3 gene to chromosome 12 and confirmed the previous assignment of the β1 gene to chromosome 1. These results were confirmed and extended by using in situ chromosome hybridization, which permitted the regional localization of the β1 gene to 1pter → p31.2 and the β3 gene to 12pter → p12.3. Digestion of human genomic DNA with 10 restriction enzymes failed to disclose a restriction fragment length polymorphism for the β3 gene. These data indicate that there is considerable diversity in the genomic organization of the β subunit family.
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