GENETICS OF GAMBIAE SUSCEPTIBILITY TO PLASMODIUM

拟议工作的长期目标是自然识别 影响疟原虫发育的蚊子发生机制 西非媒介冈比亚按蚊体内的恶性疟原虫。 这些 机制可能包括载体免疫应答以及变体免疫应答。 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生物学的 病媒与寄生虫之间的关系， 制定一项新的疟疾控制战略。 具体目标是：1）确定主要的安。冈比亚遗传基因座 控制自然疟疾中对恶性疟原虫的易感性 西非马里的输电系统。 全基因组扫描将是 在野生安氏按蚊的大谱系中进行。冈比亚。 将检测到位置 通过中肠卵囊数量与多位点的遗传连锁 微卫星基因型10厘摩分辨率。 2)分析 相同的蚊子谱系以确定两种已知蚊子的影响 在自然条件下，P. 恶性疟原虫传播系统，通过遗传连锁分析， 微卫星标记 此外，一项实验室研究将确定 寄生虫种特异性的溶解难治性反应的一个。 冈比亚，其中寄生虫在中肠上皮内被破坏 细胞 3)确定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 感染蚊的家系分析。 自然人口的一个。 冈比亚人根据染色体分为遗传亚群 倒置。 初步证据表明， 疟疾病媒能力。 实验室研究表明，具有简单 遗传基础对寄生虫的发育有很大影响。 然而，实验室系统可以脱离自然的生物学， 疟疾传播的重要方式。 载体机制 尚未研究自然界中对疟原虫的易感性。 该项目将是第一次检查自然发生的 在P. 恶性疟原虫传播系统

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.