GENETICS OF GAMBIAE SUSCEPTIBILITY TO PLASMODIUM

拟议工作的长期目标是自然地识别 影响疟原虫发育的蚊虫发生机制 西非冈比亚按蚊病媒体内的恶性疟原虫。这些 机制可能包括媒介免疫反应和变种 参与关键病媒-寄生虫分子相互作用的分子。 了解这些机制将有助于阐明 病媒和寄生虫之间的关系，可用于 制定新的疟疾控制战略。 具体的目标是：1)确定主要的AN。冈比亚亚种遗传基因座 控制自然疟疾中对恶性疟原虫的易感性 西非马里的传播系统。全基因组扫描将是 在野生蚂蚁的大型家系中进行。冈比亚亚目。将检测到基因座 中肠卵囊数与多基因座的遗传连锁 10厘米摩根分辨率的微卫星基因。2)分析 确定同一蚊子谱系对两个已知蚊子的影响 天然P。 恶性疟原虫传播系统的遗传连锁分析 微卫星标记。此外，一项实验室研究将确定 An.裂解难治反应的寄生虫种类特异性。 冈比亚，其中寄生虫在中肠上皮内被破坏 细胞。3)确定AN的染色体类型之间的关联。 冈比亚与恶性疟原虫易感性的细胞遗传学研究 被感染蚊子家系的分析。按蚊的自然种群。 冈比亚亚族根据染色体被细分为遗传亚群 反转。初步证据表明，这些形式可能在 疟疾病媒能力。 实验室研究表明，矢量机构具有简单的 遗传基础在很大程度上影响寄生虫的发育效率。 然而，实验室系统可能会脱离自然界的生物学。 疟疾传播的重要途径。向量的机制 自然界对疟疾寄生虫的易感性尚未得到研究。 这个项目将是对自然发生的 蚊虫对疟疾寄生虫耐药机制的研究 恶性疟传播系统。

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.