Genomic Organization and Chromosomal Assignment of the Human Voltage-Gated Na+ Channel β1 Subunit Gene (SCN1B)

Abstract Voltage-gated sodium (Na + ) channels are essential for the generation and propagation of action potentials in striated muscle and neuronal tissues. Biochemically, Na + channels consist of a large α subunit and one or two smaller β subunits. The α subunit alone can exhibit all of the functional attributes of a voltage-gated Na + channel, but requires a β 1 subunit for normal inactivation kinetics. While genetic mutations in the skeletal muscle Na + channel α-subunit gene can cause human disease, it is not known whether hereditary defects in the β 1 subunit underlie any inherited syndromes. To help explore this further, we have carried out an analysis of the detailed structure of the human β 1 subunit gene ( SCN1B ) including the delineation of intron-exon boundaries hy genomic DNA cloning and sequence analysis. The complete coding region of SCN1B is found in ∼9.0 kb of genomic DNA and consists of five exons (72 to 749 bp) and four introns (90 bp to 5.5 kb). Using a 15.9-kb genomic SCN1B clone, we assigned the gene to the long arm of chromosome 19 (19q13.1-q13.2) by fluorescence in situ hybridization. An intragenic polymorphic (TTA) n repeat that is positioned between two tandem Alu repetitive sequences was also characterized. The (TTA) n repeat exhibits 5 distinct alleles and a heterozygosity index of 0.59. This information should be useful in evaluating SCN1B as a candidate gene for hereditary disorders affecting membrane excitability.