GENETICS OF GAMBIAE SUSCEPTIBILITY TO PLASMODIUM

冈比亚对疟原虫易感性的遗传学

• 批准号: 2887657
• 负责人: KENNETH D VERNICK
• 金额: $ 44.08万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-05 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887657
• 关键词: Africa; Anopheles; Plasmodium falciparum; chickens; cytogenetics; disease vectors; genetic markers; genetic susceptibility; host organism interaction; human subject; linkage mapping; malaria; quantitative trait loci

The long term objective of the proposed work is to identify naturally occurring mosquito mechanisms that affect the development of Plasmodium falciparum in the vector, Anopheles gambiae, in West Africa. These mechanisms may include vector immune responses as well as variant molecules involved in critical vector-parasite molecular interactions. Understanding these mechanisms will illuminate the biology of the relationship between vector and parasite and could be useful in developing a novel malaria control strategy. The specific aims are to: 1) Identify the major An. gambiae genetic loci that control susceptibility to P. falciparum in the natural malaria transmission system in Mali, West Africa. A genome-wide scan will be conducted in large pedigrees of wild An. gambiae. Loci will be detected by genetic linkage of midgut oocyst number with a multilocus microsatellite genotype at 10 centiMorgan resolution. 2) Analyze the same mosquito pedigrees to determine the influence of two known refractory mechanisms, encapsulation and lysis, in the natural P. falciparum transmission system, by genetic linkage analysis with microsatellite markers. In addition, a laboratory study will determine the parasite species-specificity of the lysis refractory response of An. gambiae, in which parasites are destroyed within midgut epithelial cells. 3) Determine the association between chromosomal forms of An. gambiae and susceptibility of P. falciparum infection, by cytogenetic analysis of the infected mosquito pedigrees. Natural populations of An. gambiae are subdivided into genetic subgroups based on chromosome inversions. Preliminary evidence suggests the forms may differ in malaria vector competence. Laboratory studies have shown that vector mechanisms with a simple genetic basis can greatly affect the efficiency of parasite development. However, laboratory systems can depart from the biology of natural malaria transmission in important ways. Mechanisms of vector susceptibility to malaria parasites in nature have not been studied. This project will be the first examination of naturally-occurring mechanisms of mosquito refractoriness to malaria parasites in the P. falciparum transmission system.

拟议工作的长期目标是自然地识别 影响疟原虫发育的蚊子机制 西非的冈比亚按蚊病媒中的恶性疟原虫。 这些 机制可能包括载体免疫反应以及变异 参与关键载体-寄生虫分子相互作用的分子。 了解这些机制将阐明其生物学原理 媒介和寄生虫之间的关系，可能有助于 制定新的疟疾控制战略。 具体目标是： 1) 确定主要 An。冈比亚遗传位点 控制自然疟疾中恶性疟原虫的易感性 西非马里的输电系统。 全基因组扫描将 在野生安的大谱系中进行。冈比亚。 将检测到位点 通过中肠卵囊数量与多位点的遗传连锁 10 厘摩分辨率的微卫星基因型。 2）分析 相同的蚊子谱系来确定两个已知的影响 天然 P 中的难处理机制、包封和裂解。 恶性疟原虫传播系统，通过遗传连锁分析 微卫星标记。 此外，实验室研究将确定 An 裂解不应反应的寄生虫物种特异性。 冈比亚，中肠上皮内的寄生虫被消灭 细胞。 3)确定An的染色体形式之间的关联。 冈比亚和恶性疟原虫感染的易感性，通过细胞遗传学 受感染蚊子谱系分析。 An 的自然种群。 冈比亚人根据染色体细分为遗传亚组 倒置。 初步证据表明，形式可能有所不同 疟疾媒介能力。 实验室研究表明，矢量机制具有简单的 遗传基础可以极大地影响寄生虫发育的效率。 然而，实验室系统可能偏离自然的生物学 疟疾传播的重要途径。 载体机制 尚未研究对自然界中疟原虫的易感性。 该项目将是首次对天然存在的物质进行检查 蚊子对疟疾寄生虫的抵抗机制。 恶性疟原虫传播系统。