STRUCTURE, EVOLUTION, AND POLYMORPHISMS OF THE HUMAN APOLIPOPROTEIN-A4 GENE (APOA4)
STRUCTURE, EVOLUTION, AND POLYMORPHISMS OF THE HUMAN APOLIPOPROTEIN-A4 GENE (APOA4)
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DOI：
10.1073/pnas.83.22.8457
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发表时间：
1986-11-01
影响因子：
11.1
通讯作者：
ANTONARAKIS, SE
中科院分区：
文献类型：
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作者：
KARATHANASIS, SK;OETTGEN, P;ANTONARAKIS, SE
编码血浆脂质转运系统的三种蛋白质的基因载脂蛋白A1 （APOA1）、C3 （APOC3）和A4 （APOA4）在人类11号染色体的长臂上紧密相连并串联在一起。本研究分离并鉴定了人类APOA4基因。与包含三个内含子的APOA1和APOC3基因不同，APOA4基因只包含两个内含子。中断APOA1和APOC3 mRNA的5‘’非编码区的内含子在APOA4 mRNA的相应位置缺失。然而，与APOA1和APOC3基因类似，APOA4基因的内含子分离了APOA4中编码信号肽和两性结构域的核苷酸序列。这些结果表明，APOA1、APOC3和APOA4基因来自一个共同的进化祖先，并表明在进化过程中，APOA4基因失去了一个祖先内含子。两个限制性内切酶位点，位于APOA4基因的第二个内含子的Xba I和位于APOA4基因的9千碱基3‘’的不同Xba I，在地中海和北欧人群中是多态性的。单倍型分析表明，即使这些多态性位点位于9千碱基内，它们也不表现出显著的非随机关联。最后，对APOA-APOC3缺乏症合并早发性冠状动脉疾病患者的DNA进行限制性内切图谱分析，结果表明该患者APOA4基因结构正常。
The genes coding for three proteins of the plasma lipid transport system-apolipoproteins A1 (APOA1), C3 (APOC3), and A4 (APOA4)-are closely linked and tandemly organized on the long arm of human chromosome 11. In this study the human APOA4 gene has been isolated and characterized. In contrast to APOA1 and APOC3 genes, which contain three introns, the APOA4 gene contains only two. An intron interrupting the 5'' noncoding region of the APOA1 and APOC3 mRNAs is absent from the corresponding position of the APOA4 mRNA. However, similar to APOA1 and APOC3 genes, the introns of the APOA4 gene separate nucleotide sequences coding for the signal peptide and the amphipathic domains in APOA4. These results suggest that the APOA1, APOC3, and APOA4 genes were derived from a common evolutionary ancestor and indicate that during evolution the APOA4 gene lost one of its ancestral introns. Two restriction endonucleases sites, an Xba I located in the second intron of the APOA4 gene and a different Xba I located 9 kilobases 3'' to the APOA4 gene, are polymorphic in Mediterranean and Northern European populations. Haplotype analysis indicated that even though these polymorphic sites are located within 9 kilobases they do not display significant nonrandom association. Finally, restriction mapping analysis of DNA from a patient with combined APOA-APOC3 deficiency and premature coronary artery disease indicated that this patient has a structurally normal APOA4 gene.