RFLP MAPPING OF PLASMODIUM REFACTORY GENES IN MOSQUITOES

疟疾仍然是对人类健康的重大威胁，全世界每年约有4亿人受到感染，约有200万人死亡，主要是热带非洲的儿童。由于多种杀虫剂抗药性蚊子的出现和恶性疟原虫氯喹耐药性的全球传播，疟疾控制计划的有效性已经大大降低。此外，开发疫苗的努力在不久的将来提供解决这一疾病问题的希望渺茫。拟议研究的长期目标是鉴定、分离和表征与蚊子对疟原虫的易感性和/或难耐性相关的基因，并利用这些信息制定旨在破坏寄生虫生命周期的新型疟疾疾病控制策略。该项目的目标是基于与疟原虫耐药性相关的基因可以用定位克隆技术鉴定和分离的一般假设。这些基因的鉴定将通过以下途径加强疟疾疾病的控制工作：1)通过确定参与生化途径的特定基因来鉴定新的病原体；2)鉴定用于生产基因工程的、难治性蚊子菌株的合适候选基因。本研究考察了埃及伊蚊及其与疟疾寄生虫鸡状疟原虫的遗传关系，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)确定包含影响疟原虫载体能力的基因的精细尺度基因组区域，以及(2)分离和鉴定重新定义的QTL区域中包含的基因。

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.