Genetic basis of salt tolerance in Anopheles gambiae s.l.

描述（由申请人提供）：每年约有80万人死于疟疾。虽然目前可用的病媒控制工具主要是蚊帐和室内杀虫剂喷洒大大减少了疟疾病例和死亡，但由于抗药性的威胁，这种公共卫生方面的成功是脆弱的。此外，即使没有抗药性，现有的工具也不足以在疟疾高发和稳定的地方阻断疟疾传播，如在非洲许多地区。开发新的针对病媒的工具势在必行，但这取决于对蚊子生态和行为的理解，而这是目前所缺乏的。在这里，我们研究盐水耐受性，在许多重要的疟疾病媒中发现的一种特性，在决定蚊子的栖息地利用和生态分布方面起着关键作用，从而对疟疾传播做出贡献。我们的目标是剖析非洲疟疾病媒An耐盐水的遗传基础。merus，主要载体An的近亲。冈比亚。我们将解剖盐水耐受性在安。通过两个互补的具体目标：1。研究了盐胁迫下黑曲霉耐盐性的QTL定位。merus使用多个菌落的An. merus和安氏隐翅虫An.冈比亚，我们已经表明，一个。merus可以与An区分开。gambiae及其F_1杂种在50%海水中存活。我们将应用一种新的基于Illumina的基因分型方法来绘制在暴露于50%海水中的个体回交后代中的重组断点，以定位控制耐盐性的QTL区域。2.确定与淡水和盐水中发育相关的差异基因表达。merus生存在50%的海水是依赖于暴露的发育时间，和定位的离子转运蛋白（Na/K ATP酶）在直肠中不同的新鲜与盐水饲养的幼虫。我们假设这些观察结果是由于暴露于盐水引发的差异表达。我们将测试这一假设，并通过比较新鲜与盐水饲养的幼虫之间的全球基因表达来识别候选基因。在为期两年的项目结束时，QTL定位和差异基因表达的综合证据将引导我们找到有助于疟疾载体An耐盐性的候选基因和/或候选基因区域。merus。不像其他复杂的生态，行为和生活史特征的流行病学的重要性，可能是多基因，盐水耐受性是相对听话，可能由几个主要位置与大的影响，和简单的测定。使用下一代基因组工具剖析这种适应性特征的遗传基础的能力为未来努力了解这些媒介蚊子适应异质和不断变化的环境的机制奠定了基础，开辟了媒介控制的新途径。 公共卫生相关性：目前可用的防治疟疾工具不足以在疟疾高发和稳定的地区阻断疾病传播，如非洲许多地区。开发新的针对病媒的工具势在必行，但这取决于对蚊子生态和行为的理解，而这是目前所缺乏的。在这里，我们研究盐水耐受性，在许多重要的疟疾病媒中发现的一种特性，在决定栖息地的使用和生态分布中起着关键作用，因此在沿海地区的疟疾传播。

DESCRIPTION (provided by applicant): About 800,000 people die each year from malaria. While the currently available vector control tools-mainly bed nets and indoor insecticide spraying-are substantially reducing malaria cases and deaths, this public health success is fragile due to the threat of resistance. Moreover, even without resistance, existing tools are insufficient to interrupt malaria transmission where it is high and stable, as in many parts of Africa. The development of new vector-targeted tools is imperative, but depends on an understanding of mosquito ecology and behavior that is currently lacking. Here we study saltwater tolerance, a trait found in numerous important malaria vectors that plays a key role in determining habitat use and ecological distribution of mosquitoes, and thus their contribution to malaria transmission. Our objective is to dissect the genetic basis of saltwater tolerance in the African malaria vector An. merus, a close relative of the primary vector An. gambiae. We will dissect saltwater tolerance in An. merus through two complementary specific aims: 1. Genetically map QTLs that contribute to salinity tolerance in An. merus Using multiple colonies of An. merus and An. gambiae, we have shown that An. merus can be distinguished from An. gambiae and their F1 hybrids by survival in 50% seawater. We will apply a novel Illumina-based genotyping approach to map recombination breakpoints in individual backcross progeny that do/do not survive exposure to 50% seawater, to localize QTL regions that control salinity tolerance. 2. Identify differential gene expression associated with development in fresh vs. saltwater We have shown that the ability of An. merus to survive in 50% seawater is dependent upon developmental timing of exposure, and that the localization of an ion transporting protein (Na/K ATPase) in the rectum differs in fresh vs. saltwater-reared larvae. We hypothesize that these observations are due to differential expression triggered by exposure to saltwater. We will test this hypothesis and identify candidate genes by comparing global gene expression between fresh vs. saltwater-reared larvae. At the end of the two-year project, combined evidence from QTL mapping and differential gene expression will lead us to candidate genes and/or candidate gene regions that contribute to salinity tolerance in the malaria vector An. merus. Unlike other complex ecological, behavioral and life history traits of epidemiological importance that are probably polygenic, saltwater tolerance is relatively tractable, likely governed by a few major loc with large effects, and simple to assay. The ability to dissect the genetic basis of this adaptive trait using next generation genomic tools lays the groundwork for future efforts to understand the mechanisms by which these vector mosquitoes adapt to a heterogeneous and changing environment, opening up new avenues of vector control. PUBLIC HEALTH RELEVANCE: Currently available tools to combat malaria are insufficient to interrupt disease transmission where it is high and stable, as in many parts of Africa. The development of new vector-targeted tools is imperative, but depends on an understanding of mosquito ecology and behavior that is currently lacking. Here we study saltwater tolerance, a trait found in numerous important malaria vectors that plays a key role in determining habitat use and ecological distribution, and hence malaria transmission in coastal regions.