Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum, the malignant human malaria parasite
Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum, the malignant human malaria parasite
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DOI：
10.1016/s0378-1119(99)00069-4
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发表时间：
1999-04-01
期刊：
影响因子：
3.5
通讯作者：
Tanabe, K
中科院分区：
文献类型：
--
作者：
Sakihama, N;Kimura, M;Tanabe, K
恶性疟原虫裂殖子表面蛋白-1（MSP-1）的C-末端、富含半胱氨酸的19 kDa结构域是宿主体液免疫的靶标，因此是疟疾疫苗候选物。尽管寄生虫分离株中19 kDa结构域的变异有限，但19 kDa结构域与MSP-1其他部分之间的三级结构依赖性分子内关联被认为通过允许针对其表位的保护性和非保护性抗体的竞争性结合而参与免疫逃避，这些表位在构象上非常接近，但在一级结构上分离。由于等位基因重组可以解释Msp-1基因的主要变异性，我们研究了5 '和3'区域的多态性位点之间是否发生连锁不平衡，后者编码19 kDa结构域。从184个泰国举行的分离株，我们选择了69个分离株与一个单一的等位基因型在6个可变区的Msp-1确定基于PCR的等位基因分型。所有分离株在区组6至16中均未显示重组证据，而在区组2至6中重组明显。3 ′-区的测序揭示了在区段17中的两个潜在重组位点。在5 '-和3'-区域的多态位点之间观察到强烈的连锁不平衡。这种不平衡的强度与基因座之间的距离无关。我们讨论了可能的作用，上位选择特定的关联类型（单倍型）的Msp-1。(C)1999 Elsevier Science B. V.保留所有权利。
The C-terminal, cysteine-rich 19 kDa domain of merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a target of the host's humoral immunity and thus a malaria vaccine candidate. Although variation in the 19 kDa domain is limited among parasite isolates, tertiary structure-dependent intramolecular associations between the 19 kDa domain and other parts of MSP-1 are suggested to be involved in immune evasion by allowing competitive binding of protective and non-protective antibodies directed to their epitopes, which are conformationally in close proximity but separated at the primary structure. Since allelic recombination can account for the major variability of the Msp-1 gene, we examined whether linkage disequilibrium occurs between polymorphic loci in the 5'- and the 3'-region, the latter encoding the 19 kDa domain. From 184 Thai held isolates, we selected 69 isolates with a single allelic type in six variable blocks of Msp-1 as determined by PCR-based allelic typing. All the isolates showed no evidence of recombination in blocks 6 to 16, whereas recombination was apparent in blocks 2 to 6. Sequencing of the 3'-region revealed two potential recombination sites in block 17. Strong linkage disequilibrium was seen between polymorphic loci in the 5'- and 3'-regions. The strength of this disequilibrium did not correlate with distance between loci. We discuss the possible role of epistatic selection on particular association types (haplotypes) of Msp-1. (C) 1999 Elsevier Science B.V. All rights reserved.