Genetic polymorphism and diversity of Plasmodium vivax malaria

间日疟原虫疟疾的遗传多态性和多样性

• 批准号: 7463921
• 负责人: Dyann F Wirth
• 金额: $ 5.92万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7463921
• 关键词: Accounting; Admission activity; Affect; Africa; African; Antigens; Archives; Area; Asia; Base Sequence; Bioinformatics; Biology; Candidate Disease Gene; Child; Chromosomes; Chromosomes, Human, Pair 2; Code; Codon Nucleotides; Communities; Comparative Genomic Analysis; Count; Country; DNA; DNA Sequence; Data; Depth; Development; Disease; Economics; Gene Duplication; Gene Expression; Gene Frequency; Genes; Genetic Polymorphism; Genetic Structures; Genetic Variation; Genome; Genomics; Genotype; Geographic Locations; Grant; Health; Hospitals; Human; Individual; Infection; Introns; Laboratories; Linkage Disequilibrium; Malaria; Malaria Vaccines; Maps; Methods; Microsatellite Repeats; Morbidity - disease rate; Mutation; Nucleotides; Oligonucleotide Microarrays; Organism; Pan Genus; Pan troglodytes; Parasites; Parents; Pathogenesis; Patients; Pattern; Phylogenetic Analysis; Plasmodium vivax; Polymerase Chain Reaction; Polymorphism Analysis; Population; Population Biology; Population Genetics; Productivity; Public Health; Quality of life; Range; Rate; Recording of previous events; Reporting; Sampling; Single Nucleotide Polymorphism; Site; South America; Sri Lanka; Structure; Testing; Time; United States National Institutes of Health; Vaccines; Variant; Vivax Malaria; Work; apical membrane; base; density; design; disorder control; genome sequencing; genome-wide analysis; mortality; neglect; novel; paralogous gene; parent grant; pressure; serial analysis of gene expression

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.

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，因为它在世界热带地区流行，导致高发病率和死亡率。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常见的物种。尽管很少致命，但间日疟原虫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 2/3 的地区流行，并被列为该流行地区入院的前四种原因之一。尽管恶性疟原虫和间日疟原虫都会在斯里兰卡引起疟疾，但后者占过去十年报告的所有疟疾感染的 70-80% 或更多。基于间日疟原虫 SAL-1 株的基因组序列已基本完成，并向公众开放 (http:www.tigr.org/tdb/e2k1/pva1/)。然而，它没有提供有关这种寄生虫的遗传多样性或多态性的任何信息。遗传变异是生物体发病机制的核心，并严重阻碍了有效疟疾疫苗的开发进展。因此，本研究中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进行有效估计具有重要意义。本研究提出了一项深入分析，包括通过对 4 个不同地理来源的间日疟原虫菌株中的 4 个间日疟原虫菌株进行基于 PCR 的测序，对间日疟原虫基因组内 300 kb 片段中的单核苷酸多态性 (SNP) 进行鉴定。除了基因分型研究外，还计划对诺氏疟原虫（与间日疟原虫密切相关的物种）中的相应序列进行比较基因组分析，从而能够分析来自不同地理区域的患者分离株中的全基因组微卫星（MS）多态性以及染色体目标区域（300 kb）内的MS和单核苷酸多态性。这将使我们能够了解自然变异、种群结构、遗传多样性和多态性，包括等位基因频谱的范围和最近存档的代表全球疟疾流行区的野外寄生虫分离株的连锁不平衡模式，从而更好地了解这种被忽视的寄生虫物种的生物学、种群遗传学和进化历史。疟疾是世界许多地区最重要的公共卫生问题之一，因为它导致高发病率和死亡率，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策略，以对抗这种主要影响发展中国家贫困社区的毁灭性疾病。