Malaria Parasite Sexual Development, Drug Resistance, an

疟疾基因组股利用疟疾寄生虫基因组数据库，开发新的资源，研究抗药性机制、寄生虫性发育过程中的基因调控以及寄生虫种群多样性和进化。这方面的一个项目是用数百个微卫星标记对恶性疟原虫田间分离株进行基因分型，以确定与耐药性相关的染色体位点。一个世界范围内收集的90个寄生虫分离株已被分型与342个标记，并揭示了，除了候选位点的耐药性，寄生虫基因组结构，多样性，药物选择性扫描，和进化关系的重要信息。另一个项目是收集来自寄生虫转运蛋白基因的单核苷酸多态性（SNP）以及SNP与药物反应的关联。已经鉴定了多种候选基因。我们还在开发用于大规模研究的资源，包括：1）全基因组SNP数据库，每个基因至少有一个SNP，与MS标记整合; 2）全球寄生虫分离株收集; 3）。恶性疟原虫单倍体基因组关联分析的统计和计算机程序。从四个寄生虫分离株中已经测序了大约400个染色体2和3上的基因，并且已经鉴定了数百个SNP。有了这些资源，我们可以集中精力进行表型评估和测量，包括寄生虫对各种抗疟药和营养变化的反应。这些工具将用于研究流行地区的寄生虫种群遗传学和传播动态。我们还在研究线粒体基因组的多态性，以推断寄生虫的种群历史，包括迁移和种群扩张。我们实验室的另一个研究兴趣是通过使用微阵列和蛋白质组学方法进行表达分析来研究基因功能和基因相互作用。我们还使用来自寄生虫基因组的6300个寡核苷酸打印了微阵列载玻片，并做了一些初步的杂交实验。在鉴定候选基因后，将进行详细的生化和遗传表征。

The Malaria Genomic Unit uses the malaria parasite genome databases and develops new resources to study the mechanism of drug resistance, gene regulation during parasite sexual development, and parasite population diversity and evolution. One project in this direction is the genotyping of Plasmodium falciparum field isolates with hundreds of microsatellite markers to identify chromosome loci associated with drug resistance. A worldwide collection of 90 parasite isolates have been typed with 342 markers and have revealed, in addition to candidate loci for drug resistance, important information on parasite genome structure, diversity, drug selective sweeps, and evolutionary relationships. Another project is the collection of single nucleotide polymorphisms (SNP) from the parasite transporter genes and the association of the SNP to drug responses. Various candidate genes have been identified. We are also developing resources for large scale studies to include: 1) A genome-wide SNP database with at least one SNP per gene, integrated with MS markers; 2) A worldwide collection of parasite isolates; 3). Statistical and computer programs for association analysis specific for the haploid genome of P. falciparum. About 400 genes on chromoosme 2 and 3 have been sequenced from four parasite isolates and hundreds of SNP have been identified. With these resources, we can concentrate on phenotype evaluation and measurement, including parasite responses to various antimalarials and nutrient changes. These tools will be used to study parasite population genetics and transmission dynamics in endemic areas. We are also studing polymorphisms in the mitochndria genome to infer the parasite population history, including migration and population expansion. Another research interest of our lab is the study of gene function and gene interactions by expressional analysis using microarray and proteomic methods. We have also printed microarray slides using 6300 oligonucleotides derived from the parasite genome and have done some preliminary hybridization experiments. Detailed biochemical and genetic characterization will follow after identification of candidate genes.