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: 7291160
• 负责人: Dyann F Wirth
• 金额: $ 2.96万
• 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/7291160
• 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，因为它在世界上流行的热带地区造成高发病率和死亡率。在引起人类疟疾的4种物种中，间日疟原虫是热带非洲以外最流行的物种。虽然间日疟原虫很少致命，但它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，并被列为流行地区入院的前四个原因之一。虽然恶性疟原虫和间日疟原虫在斯里兰卡都引起疟疾，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菌株的间日疟原虫基因组序列几乎是完整的，并且可供公众使用（http：www.tigr.org/tdb/e2k1/pva1/）。然而，它没有提供关于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，严重阻碍了有效疟疾疫苗的开发。因此，本研究提出的寄生虫种群之间的遗传多样性评估具有重要意义，更好地了解其生物学，疾病控制策略的发展，并作出有效的估计，其起源。本研究通过对4株不同地理来源的间日疟原虫基因组内300 kb片段进行PCR测序，对该区域进行了深入分析，包括单核苷酸多态性（SNP）鉴定。除了基因分型研究之外，还计划在诺氏疟原虫（一种与间日疟原虫密切相关的种属）中进行比较基因组分析和相应序列分析，以分析来自不同地理区域的患者分离株的全基因组微卫星（MS）多态性以及染色体靶区域（300 kb）内的MS和单核苷酸多态性。这将有助于了解自然变异、种群结构、遗传多样性和多态性，包括等位基因频率谱的范围和最近存档的代表全球疟疾流行区的田间寄生虫分离株的连锁不平衡模式，这反过来又有助于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。疟疾是世界上许多地区最重要的公共卫生问题之一，因为它造成的高发病率和死亡率，特别是在幼儿中。更好地了解致病寄生虫的遗传结构及其变化，这项拟议研究的目标，将使有效的控制战略，以打击这种破坏性的疾病，主要影响发展中国家的贫困社区。