RFLP MAPPING OF PLASMODIUM REFACTORY GENES IN MOSQUITOES

疟疾仍然是对人类健康的重大威胁，全世界约有4亿人感染，每年约有200万人死亡，其中主要是热带非洲的儿童。 由于出现了对多种杀虫剂具有抗药性的蚊子种群，以及恶性疟原虫对氯喹的抗药性在世界范围内蔓延，疟疾控制计划的有效性已大大降低。 此外，疫苗开发方面的努力在不久的将来为这种疾病问题提供解决方案方面几乎没有希望。 拟议研究的长期目标是鉴定、分离和表征与蚊子物种对疟原虫寄生虫的易感性和/或难治性相关的基因，并利用这些信息开发旨在破坏寄生虫生命周期的新型疟疾疾病控制策略。 本项目的目标是基于一般的假设，即与疟原虫难治性相关的基因可以使用定位克隆技术进行鉴定和分离。 这些基因的表征将通过以下方式增强疟疾疾病控制努力：1）通过确定生物化学途径中的特定基因参与来鉴定新型药剂，或2）鉴定用于产生遗传工程化的难治性蚊子品系的合适候选基因。 该研究考察了蚊子埃及伊蚊及其与疟疾寄生虫鸡疟原虫的遗传关系，作为阐明遗传控制机制的模型系统，因为这种蚊子拥有丰富的遗传信息，而且这种寄生虫与主要的人类疟疾寄生虫恶性疟原虫有密切的系统发育关系。 该项目的具体目标是：（1）确定含有影响疟原虫载体能力的基因的基因组区域的精细比例图，以及（2）分离和鉴定重新定义的QTL区域内所含的基因。

Malaria remains a significant threat to human health, with about 400 million people infected worldwide and about 2 million deaths per year, primarily children from tropical Africa. The effectiveness of malaria control programs has been significantly reduced due to the emergence of multiple-pesticide resistant mosquito populations and the worldwide spread of chloroquine resistance in Plasmodium falciparum. In addition, efforts toward vaccine development have shown little promise in providing a solution to this disease problem in the near future. The long- term objectives of the proposed research are to identify, isolate and characterize genes associated with the susceptibility and/or refractoriness of mosquito species to Plasmodium parasites, and to use this information to develop novel malaria disease control strategies aimed toward disrupting the parasite life cycle. The objectives of this project are based on the general hypothesis that genes associated with Plasmodium refractoriness can be identified and isolated using positional cloning techniques. The characterization of these genes will enhance malaria disease control efforts by 1) identifying novel agents through determining specific gene involvement in biochemical pathways or 2) identifying suitable candidate genes for the production of genetically engineered, refractory mosquito strains. The research examines the mosquito Aedes aegypti and its genetic relationship with the malarial parasite Plasmodium gallinaceum as a model system for elucidating genetic control mechanisms, because of the wealth of genetic information available for this mosquito and the close phylogenetic relationship of this parasite and the major human malarial parasite P. falciparum. The specific aims of the project are: (1) Fine-scale map genome regions identified as containing genes that influence Plasmodium vector competence, and (2) Isolate and identify genes contained within the redefined QTL regions.