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）：由于它在世界热带地区引起的高发病和死亡率，疟疾被认为是最具破坏性的全球健康问题之一。在引起人类疟原虫疟原虫的四种物种中，是非洲热带非洲以外的最普遍的物种。尽管很少致命，但维瓦克斯会导致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。在斯里兰卡，这项研究的主要合作地点，疟疾是该国2/3的地方性的，被计为在其流行地区入院的前四个原因之一。尽管在斯里兰卡引起疟原虫和维瓦克斯的疟疾，但后一种物种占过去十年中报告的所有疟疾感染中的70-80％或更多。基于P.Vivax的SAL-1菌株的P.Vivax基因组序列几乎是完整的，可以向公众使用（http：www.tigr.org/tdb/e2k1/pva1/）。但是，它没有提供有关该寄生虫的遗传多样性或多态性的任何信息。遗传变异对于生物体的发病机理至关重要，并且在开发有效的疟疾疫苗方面已经显着阻碍了进步。因此，这项研究中提出的寄生虫种群之间遗传多样性的评估对于更好地理解其生物学，制定疾病控制策略并就其起源进行有效的估计具有很大的相关性。这项研究提出了深入的分析，包括在p.vivax基因组内300 kb段中通过PCR基于PCR的测序在4 p.vivax菌株中基于PCR基因组的测序，在具有不同地理学起源的4 p.vivax菌株中对单个核苷酸多态性（SNP）进行了鉴定。比较基因组分析以及在P. knowlesi中的相应序列，除了基因分型研究外，还计划了与基因组宽的微卫星（MS）多态性分析以及MS和单核苷酸多态性分析的基因组分型研究，以及在靶向区域内（300 kb）（300 kb）（300 kb）（300 kb）的colomosome ecoprication necoption necoption necoption necoption necoption necoption ernation necoption necoption。这将使人们能够理解自然变异，人口结构，遗传多样性和多态性，包括等位基因频谱的范围以及最近存档的田间寄生虫分离株中代表全球疟疾地方性区域的链接不平衡的模式，这反过来又可以更好地了解生物学，遗传学和进化史。疟疾是世界许多地方最重要的公共卫生问题之一，因为它引起的发病率高和死亡率，尤其是在幼儿中。对这项拟议的研究的目的，更好地了解遗传结构及其在病因寄生虫中的变化将使有效的控制策略能够打击这种毁灭性疾病，主要影响发展中国家贫困社区。