RFLP MAPPING OF PLASMODIUM REFRACTORY GENES IN MOSQUITOS

蚊子中疟原虫耐药基因的 RFLP 作图

• 批准号: 2886784
• 负责人: DAVID W SEVERSON
• 金额: $ 22.4万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2886784
• 关键词: Aedes; Anopheles; Plasmodium; arthropod borne communicable disease; arthropod nonpollutant control; chickens; communicable disease control; disease vectors; gene expression; genetic manipulation; host organism interaction; laboratory rabbit; linkage mapping; malaria; molecular cloning; restriction fragment length polymorphism

Each year, an estimated 280 million people are affected by and 1-2 million deaths occur as a consequence of the symptoms of malaria following exposure to a Plasmodium spp. Control efforts have been limited by the lack of progress in vaccine development, development and spread of Plasmodium strains resistant to antimalarial drugs, development of pesticide resistance in mosquito vectors, and the general decline in organized mosquito vector control programs. 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, and to utilize this information to develop a malaria control strategy based on the genetic disruption of mosquito vector competence. The objectives of this project are based on the general hypothesis that genes associated with Plasmodium refractoriness can be identified and isolated via determination of their genetic linkage associations with restriction fragment length polymorphism (RFLP) markers. The research described primarily 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 knowledge available concerning the genetics of this vector and the close phylogenetic relationship of this parasite and the major human malarial parasite P. falciparum. Additionally, some of the proposed research involves a primary vector for P. falciparum, Anopheles gambiae. The specific aims of this project are: (1) to isolate genes that influence Plasmodium susceptibility in Ae. aegypti using map-based cloning techniques, (2) determine the potential of candidate genes isolated in specific aim 1 to positively or negatively influence the development of P. gallinaceum in Ae. aegypti using virus expression systems in cooperation with Colorado State University, (3) examine the potential effects of parasite-imposed selection on RFLP allele frequencies over time in laboratory populations, and (4) construct a preliminary RFLP linkage map for An. gambiae using markers developed for Ae. aegypti in cooperation with The Johns Hopkins University.

每年，估计有2.8亿人受到影响， 死亡是疟疾症状的后果， 接触疟原虫属 控制工作受到了 在疫苗开发、研制和推广方面缺乏进展， 抗疟药抗药疟原虫株， 蚊子媒介对杀虫剂的抗药性， 有组织的蚊虫病媒控制计划。的长期目标 拟议的研究是识别、分离和表征基因 与蚊子的易感性和/或难治性相关 物种，并利用这些信息来开发疟疾控制 该战略基于蚊子媒介能力的遗传破坏。 本项目的目标基于以下一般假设： 可以鉴定与疟原虫不应性相关的基因， 通过确定其与以下疾病的遗传连锁关联而分离： 限制性片段长度多态性（RFLP）标记。研究 所描述的主要是研究埃及伊蚊及其遗传 与作为模型的疟疾寄生虫鸡疟原虫的关系 系统阐明遗传控制机制，因为财富 关于该载体遗传学的现有知识和 这种寄生虫和主要的人类有密切的系统发育关系， 恶性疟原虫此外，一些建议 研究涉及恶性疟原虫的主要媒介冈比亚按蚊。 本项目的具体目标是：（1）分离影响 疟原虫在Ae.利用图位克隆技术 技术，（2）确定候选基因分离的潜力， 具体目标1积极或消极地影响体育运动的发展。 gallinaceum in Ae.埃及合作使用病毒表达系统 与科罗拉多州立大学合作，（3）研究 寄生虫对RFLP等位基因频率随时间的选择， 构建初步的RFLP连锁图谱 为了安。gambiae使用为Ae.埃及合作 与约翰霍普金斯大学合作。