Merozoite surface protein-3 alpha as a genetic marker for epidemiologic studies in Plasmodium vivax: a cautionary note.

Merozoite surface protein-3 alpha as a genetic marker for epidemiologic studies in Plasmodium vivax: a cautionary note.
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DOI:
10.1186/1475-2875-12-288
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发表时间:
2013-08-21
期刊:
影响因子:
3
通讯作者:
Escalante AA
Escalante AA
中科院分区:
医学3区
文献类型:
--
作者:
Rice BL;Acosta MM;Pacheco MA;Escalante AA

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间日疟原虫是地理上分布最广的人类疟疾寄生虫,被认为对当地控制和消除工作提出了独特的挑战。寄生虫分子标记可以提供急需的间日疟原虫种群数据,但很少有此类标记经过严格评估。广泛使用的一个标记是编码裂殖子表面蛋白 3-α (MSP-3α) 的基因,这是一种已知在间日疟原虫分离株中存在高度变异的血液阶段抗原。在这里,分析了完整的 msp-3α 基因序列样本,以评估其作为流行病学研究分子标记的效用。对来自不同地理位置的其他间日疟原虫分离株(包括一组委内瑞拉野外分离株(n = 10))进行扩增、克隆和测序,产生了 48 个完整 msp-3α 编码序列的样本。进行了标准群体遗传多样性测量的表征、系统发育分析和重组测试。这使得可以与广泛使用的聚合酶链式反应限制性片段长度多态性(PCR-RFLP)方案的计算机模拟推断出的模式进行比较。 MSP-3α 多样性的较大样本揭示了观察到的核苷酸多态性水平(在所有群体中都很高)与 PCR-RFLP 单倍型多样性模式之间的不一致。事实上,PCR-RFLP 单倍型并不能提供群体遗传多样性的信息,并且可以从常用方案中的类似条带产生相同的单倍型。 MSP-3α 单倍型之间频繁且可变的插入删除突变和反复重组的证据使遗传多样性模式的推断变得复杂,并减少了系统发育信号。 P. vivax msp-3α 的遗传多样性涉及基因内重组事件。尽管 msp-3α 的高遗传多样性使其成为一些流行病学应用的有希望的标记,但 msp-3α PCR-RFLP 分析准确追踪寄生虫的能力有限。在实施 PCR-RFLP 方法之前,需要对循环等位基因进行本地研究。此外,来自此处分析的全球样本的证据表明,此类 msp-3α PCR-RFLP 方法不适合广泛的地理研究或长时间跟踪寄生虫种群。
Plasmodium vivax is the most widespread of the human malaria parasites in terms of geography, and is thought to present unique challenges to local efforts aimed at control and elimination. Parasite molecular markers can provide much needed data on P. vivax populations, but few such markers have been critically evaluated. One marker that has seen extensive use is the gene encoding merozoite surface protein 3-alpha (MSP-3α), a blood-stage antigen known to be highly variable among P. vivax isolates. Here, a sample of complete msp-3α gene sequences is analysed in order to assess its utility as a molecular marker for epidemiologic investigations. Amplification, cloning and sequencing of additional P. vivax isolates from different geographic locations, including a set of Venezuelan field isolates (n = 10), yielded a sample of 48 complete msp-3α coding sequences. Characterization of standard population genetic measures of diversity, phylogenetic analysis, and tests for recombination were performed. This allowed comparisons to patterns inferred from the in silico simulation of a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) protocol used widely. The larger sample of MSP-3α diversity revealed incongruence between the observed levels of nucleotide polymorphism, which were high in all populations, and the pattern of PCR-RFLP haplotype diversity. Indeed, PCR-RFLP haplotypes were not informative of a population’s genetic diversity and identical haplotypes could be produced from analogous bands in the commonly used protocol. Evidence of frequent and variable insertion-deletion mutations and recurrent recombination between MSP-3α haplotypes complicated the inference of genetic diversity patterns and reduced the phylogenetic signal. The genetic diversity of P. vivax msp-3α involves intragenic recombination events. Whereas the high genetic diversity of msp-3α makes it a promising marker for some epidemiological applications, the ability of msp-3α PCR-RFLP analysis to accurately track parasites is limited. Local studies of the circulating alleles are needed before implementing PCR-RFLP approaches. Furthermore, evidence from the global sample analysed here suggests such msp-3α PCR-RFLP methods are not suitable for broad geographic studies or tracking parasite populations for an extended period of time.
DOI: 10.1186/1475-2875-9-112
发表时间: 2010-04-23
期刊: Malaria journal
影响因子: 3
作者:
Khatoon L;Baliraine FN;Bonizzoni M;Malik SA;Yan G
通讯作者: Yan G
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