Genomic organization and chromosomal assignment of the human voltage-gated Na+ channel beta 1 subunit gene (SCN1B).
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 alpha subunit and one or two smaller beta subunits. The alpha subunit alone can exhibit all of the functional attributes of a voltage-gated Na+ channel, but requires a beta 1 subunit for normal inactivation kinetics. While genetic mutations in the skeletal muscle Na+ channel alpha-subunit gene can cause human disease, it is not known whether hereditary defects in the beta 1 subunit underlie any inherited syndromes. To help explore this further, we have carried out an analysis of the detailed structure of the human beta 1 subunit gene (SCN1B) including the delineation of intron-exon boundaries by genomic DNA cloning and sequence analysis. The complete coding region of SCN1B is found in approximately 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.
Makita
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Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2372.
Sloan-Brown
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Weghuis
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DO
Ropers
H H
HH
George
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AL
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D016384:Consensus Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005091:Exons; D015698:Genomic Library; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D015222:Sodium Channels / Q000235:genetics*
D017931:DNA Primers; D046911:Macromolecular Substances; D015222:Sodium Channels; D004247:DNA