Malaria Parasite Sexual Development, Drug Resistance, an

疟疾基因组单位使用疟疾寄生虫基因组数据库并开发新的资源，以研究抗药性的机制、寄生虫性发育过程中的基因调控以及寄生虫种群的多样性和进化。在过去一年取得的进展的基础上，我们现在从恶性疟原虫1、2、4、5和14号染色体(去年报告了3号染色体)上的基因中收集了更多的单核苷酸多态(SNPs)。为了研究寄生虫的进化史和染色体单倍型，我们对来自世界各地的分离株的3号染色体上的SNPs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，并发现最近非洲的人口扩张与蚊子物种形成和人类人口增长相吻合。为了确定可能与耐药性有关的基因，我们从49个可能的转运蛋白基因中搜索SNPs，发现11个转运蛋白基因中的SNPs可能与寄生虫对氯喹和奎宁的反应有关。我们实验室的另一项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。利用基因芯片和基因定位技术，我们已经确定了一个可能在配子体发育中起关键作用的基因。在基因敲除目标基因后，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100kb DNA片段的比较表明，该寄生虫具有高度的基因组多样性，这表明该寄生虫是一个相对古老的生物体，可能对疾病控制构成一定的挑战。

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.