Isolation and characterization of the human apolipoprotein A-I gene.
Isolation and characterization of the human apolipoprotein A-I gene.
复制标题
人载脂蛋白 A-I 基因的分离和表征。
DOI：
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发表时间：
1983
影响因子：
11.1
通讯作者：
J. Breslow
中科院分区：
文献类型：
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作者：
S. Karathanasis;V. I. Zannis;J. Breslow
我们最近发现，人类载脂蛋白A-I(apo A-I)基因的遗传多态与两例严重动脉粥样硬化患者血浆高密度脂蛋白和apo A-I水平降低有关。要分析这种多态的分子基础及其对载脂蛋白A-I基因表达的可能影响，需要直接比较正常和多态的载脂蛋白A-I等位基因。本文报道了正常人载脂蛋白A-I基因的分离和鉴定，发现该基因被三个插入序列IVS-1、IVS-2和IVS-3打断，它们分别位于载脂蛋白A-I的5‘非编码区、编码载脂蛋白A-I信号肽的mRNA序列和编码成熟蛋白的序列。此外，载脂蛋白A-I基因的核苷酸序列分析还可以确定载脂蛋白A-I mRNA初级翻译产物的完整氨基酸序列。该氨基酸序列由267个残基组成，包括一个24个残基的氨基末端延伸(前段)。最后，我们发现apo A-I基因包含6个66碱基长的重复DNA片段，这表明该基因可能是通过基因内复制事件进化而来的。
We have recently shown that an inherited polymorphism occurring in the human apolipoprotein A-I (apo A-I) gene is related to decreased high density lipoprotein and apo A-I levels in the plasma of two patients with severe premature atherosclerosis. Analysis of the molecular basis of this polymorphism and its possible effects on apo A-I gene expression requires direct comparison of both normal and polymorphic apo A-I alleles. Here we report the isolation and characterization of the normal human apo A-I gene and we show that the gene is interrupted by three intervening sequences, IVS-1, IVS-2, and IVS-3, occurring in the 5' noncoding region of apo A-I mRNA, the mRNA sequence coding for the signal peptide of apo A-I, and the sequence coding for the mature protein, respectively. In addition, the nucleotide sequence analysis of the apo A-I gene allowed determination of the complete amino acid sequence of the primary translation product of apo A-I mRNA. This amino acid sequence consists of 267 residues including a 24-residue-long amino-terminal extension (preprosegment). Finally, we show that the apo A-I gene contains six 66-base-pair-long tandemly repeated DNA segments, which suggests that the gene may have evolved by intragenic duplication events.