Malaria Parasite Sexual Development, Drug Resistance, an

疟疾基因组组利用疟原虫基因组数据库，开发新的资源，研究疟原虫的耐药机制、性发育过程中的基因调控以及疟原虫种群的多样性和进化。在去年取得进展的基础上，我们现在已经从恶性疟原虫的第1、2、4、5和14号染色体（去年报告了第3号染色体）的基因中收集了更多的单核苷酸多态性（SNPs）。为了研究寄生虫的进化史和染色体单倍型，我们从世界各地收集的分离物中对3号染色体上的snp进行了基因分型。我们还完成了98个恶性疟原虫分离株的线粒体基因组测序，并发现非洲最近的种群扩张与蚊子物种形成和人口增长相一致。为了鉴定可能导致耐药的基因，我们从49个可能的转运体基因中寻找snp，发现其中11个可能与寄生虫对氯喹和奎宁的反应有关。我们实验室的另一个主要工作是研究与寄生虫性别分化相关的基因表达和调控。我们已经确定了一个基因，可能在配子体发育中发挥关键作用，使用微阵列和遗传作图。在基因敲除靶基因后，正在评估表型变化。我们还启动了一个试点项目，研究另一种人类疟疾寄生虫间日疟原虫的基因组多样性。对5个分离株约100千碱基的DNA片段的比较表明，该寄生虫具有高度多样化的基因组，表明这是一种相对古老的生物，可能对疾病控制提出一些挑战。

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. Building on progress made lasyt year, we have now collected additional single nucleotide polymrphisms (SNPs) from genes on chromosome 1, 2, 4, 5, and 14 (Chromosome 3 was reported last year) of Plasmodium falciparum. To study the evolutionary history and chromosomal haplotypes of the parasite, we have genotyped SNPs on chromosome 3 from a worldwide collection of isolates. We have also finished sequencing the mitochondrial genome from 98 P. falciparum isolates and discovered a recent population expansion in Africa coinciding with mosquito speciation and human population growth. To identify genes that may contribute to drug resistance, we searched for SNPs from 49 putative transporter genes and found that SNPs in 11 of the putative transporters could be associated with the parasite responses to chloroquine and quinine. Another major effort of our lab is to study gene expression and regulation associated with the parasite sexual differentiation. We have identified a gene that may play a key role in gametocyte development using microarray and genetic mapping. Phenotypic changes are being evaluated after genetic knockout of the target gene. We also initiated a pilot project to study genome diversity of another human malaria parasite Plasmodium vivax. Comparison of a ~100 kilo bases DNA segment from five isolates showed that the parasite has highly diverse genome, suggesting a relatively old organism that may present some challenge for disease control.