Genetic polymorphism and diversity of Plasmodium vivax malaria

描述（由申请人提供）：疟疾被认为是最具破坏性的全球健康问题之一，因为它在流行疟疾的世界热带地区发病率和死亡率很高。在引起人类疟疾的4种疟原虫中，间日疟原虫是热带非洲以外最流行的疟原虫。间日疟虽然很少致命，但会引起使人衰弱的疾病，严重影响受害者的生活质量和经济生产力。在本研究的主要合作地点斯里兰卡，疟疾在该国三分之二的地区流行，是流行地区住院的前四大原因之一。虽然恶性疟和间日疟都是斯里兰卡的疟疾病因，但在过去十年中报告的所有疟疾感染中，后一种疟疾占70-80%或更多。基于间日疟SAL-1株的间日疟基因组序列几乎完成，并可向公众提供（http:www.tigr.org/tdb/e2k1/pva1/）。然而，它并没有提供任何关于这种寄生虫的遗传多样性或多态性的信息。遗传变异是生物体发病机制的核心，严重阻碍了研制有效疟疾疫苗的进展。因此，本研究提出的寄生虫种群遗传多样性评估对于更好地了解其生物学，制定疾病控制策略以及对其起源做出有效估计具有重要意义。本研究提出了一项深入的分析，包括鉴定单核苷酸多态性（snp），在300 kb的区段内的间日疟原虫基因组的pcr测序，在4个间日疟原虫毒株具有不同的地理起源。除了基因分型研究之外，还计划对与间日疟原虫密切相关的诺氏疟原虫进行基因组比较分析和相应序列分析，以便分析来自不同地理区域的患者分离株染色体目标区域（300 kb）内的全基因组微卫星（MS）多态性以及MS和单核苷酸多态性。这将有助于了解代表全球疟疾流行区的最新存档的野外寄生虫分离物的自然变异、种群结构、遗传多样性和多态性，包括等位基因频谱范围和连锁不平衡模式，从而更好地了解这种被忽视的寄生虫物种的生物学、种群遗传学和进化史。疟疾是世界许多地区最重要的公共卫生问题之一，因为它的发病率和死亡率很高，特别是在幼儿中。这项拟议研究的目的是更好地了解致病寄生虫的遗传结构及其变化，这将有助于制定有效的控制战略，以防治这种主要影响发展中国家贫困社区的毁灭性疾病。

DESCRIPTION (provided by applicant): Malaria is considered as one of the most devastating global health problems due to the high morbidity and mortality it causes in the tropical parts of the world where it is endemic. Out of the 4 species that cause malaria in humans Plasmodium vivax is the most prevalent species outside tropical Africa. Although rarely fatal, P.vivax causes debilitating disease that severely affects the quality of life and economic productivity of the victims. In Sri Lanka, the main collaborating site for this study, malaria is endemic in 2/3rds of the country and is counted among the first four causes of hospital admissions in its endemic areas. Though both P.falciparum and P.vivax cause malaria in Sri Lanka, the latter species accounts for 70-80% or more of all malaria infections reported during the past decade. P.vivax genome sequence based on the the SAL-1 strain of P.vivax is almost complete and is available to the public (http:www.tigr.org/tdb/e2k1/pva1/). However, it does not provide any information on the genetic diversity or polymorphism of this parasite. Genetic variation is central to the pathogenesis of an organism and has significantly impeded progress towards the development of an effective malaria vaccine. Thus assessment of genetic diversity among parasite populations as proposed in this study has significant relevance for better understanding of its biology, for the development of strategies of disease control and to make valid estimations with regard to its origin. This study proposes an in depth analysis, including identification of single nucleotide polymorphisms (SNPs), in a 300 kb segment within the P.vivax genome by PCR-based sequencing of this region in 4 P.vivax strains with different geographical origins. Comparative genomic analysis together with the corresponding sequence in P.knowlesi, a closely related species to P.vivax is planned in addition to genotyping studies enabling the analysis of genome- wide microsatellite (MS) polymorphism and both MS and single nucleotide polymorphisms within the targeted region (300 kb) of a chromosome in patient isolates from varying geographical regions. This would enable the understanding of natural variation, population structure, genetic diversity and polymorphism, including the range of allele frequency spectrum and the patterns of linkage disequilibrium in recently archived field parasite isolates representing the global malaria endemic zones, which in turn would enable better understanding of the biology, population genetics and evolutionary history of this neglected parasite species. Malaria is one of the most important public health problems in many parts of world due to the high morbidity and mortality it causes, especially in young children. Better understanding of the genetic structure and its changes in the causative parasite, the objective of this proposed study, would enable the development of effective control strategies to combat this devastating disease that mostly affect the poor communities in the developing world.