GENOMIC ORGANIZATION AND CHROMOSOMAL ASSIGNMENT OF THE HUMAN VOLTAGE-GATED NA+ CHANNEL BETA(1) SUBUNIT GENE (SCN1B)
GENOMIC ORGANIZATION AND CHROMOSOMAL ASSIGNMENT OF THE HUMAN VOLTAGE-GATED NA+ CHANNEL BETA(1) SUBUNIT GENE (SCN1B)
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DOI：
10.1006/geno.1994.1551
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发表时间：
1994-10-01
期刊：
影响因子：
4.4
通讯作者：
GEORGE, AL
中科院分区：
文献类型：
--
作者：
MAKITA, N;SLOANBROWN, K;GEORGE, AL
电压门控钠(Na+)通道是横纹肌和神经元组织中动作电位产生和传播所必需的。在生物化学上，钠离子通道由一个大的α亚基和一个或两个较小的β亚基组成。α亚基本身可以表现出电压门控钠离子通道的所有功能属性，但需要一个β(1)亚基才能实现正常的失活动力学。虽然骨骼肌Na+通道α亚单位基因的遗传突变可以导致人类疾病，但目前尚不清楚β(1)亚单位的遗传缺陷是否会导致任何遗传性综合征。为了进一步探索这一点，我们对人β(1)亚单位基因(SCN1B)的详细结构进行了分析，包括通过基因组DNA克隆和序列分析来描绘内含子-外显子边界。SCN1B的完整编码区与基因组DNA的9.0kb相似，由5个外显子(72~749 bp)和4个内含子(90~5.5 kb)组成。利用一个15.9kb的基因组SCN1B克隆，通过荧光原位杂交将该基因定位于19号染色体的长臂(19q13.1-q13.2)。位于两个串联Alu重复序列之间的基因内多态(TTA)(N)重复也被鉴定。(TTA)(N)重复序列显示5个不同的等位基因，杂合度指数为0.59。这一信息将有助于评估SCN1B作为影响膜兴奋性的遗传性疾病的候选基因。(C)1994年学术出版社。
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 similar to 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. (C) 1994 Academic Press, Inc.