Ecological and genetic determinants of malaria transmitting behaviors in the Afri

描述（由申请人提供）：冈比亚按蚊（Anopheles gambiae s.s.）的基因组测序，是非洲疟疾的主要媒介之一，被吹捧为“…通过提供一种绘制、选择和利用感兴趣的基因的手段，在公共卫生方面取得突破。迄今为止，这些努力的主要重点是在实验室的模型系统中探索对疟疾寄生虫（疟原虫）易感性的遗传基础。这些往往不能很好地转化为自然界中正在发生的事情。事实上，很明显，在生态环境中检查媒介表型，因为它们在自然界中发生，对于在实际传播环境中产生与疟疾流行病学相关的结果至关重要。在本申请中，我们提出了一个整合媒介种群基因组学、生态学和媒介行为的研究计划，目的是了解对疟疾传播和控制至关重要的两种蚊子行为表型的决定因素：(1)宿主偏好和(2)成虫休息行为。我们的方法建立在实验室初步工作的相当大的基础上，已经确定了一个广泛的面板。arabiensis SNP标记，以及在坦桑尼亚进行的初步实地工作，这些工作已经确定了一系列适当的地点，这些地点已经试点了采样方法。众所周知，阿拉伯人是多种多样的。一个。将在干湿季节从坦桑尼亚Kilombero山谷的四个村庄集中收集arabiensis蚊子，以确定它们的进食和休息表型与时空变化的环境因素之间的关系（目标1）。将从个体样本中提取DNA，并从每个个体中确定多位点SNP基因型。基因型将根据表型（嗜外生与嗜内生，人饲与动物饲）进行组织，并在使用高效混合模型关联（EMMA）方法校正群体结构和遗传相关性后，分析确定每种表型的SNP等位基因关联（目标#2）。了解这些行为变化的遗传基础对于预测当前病媒控制策略可能的下游进化反应，以及开发新的控制策略至关重要，这些策略可以改进当前可用的病媒控制方法的应用和/或基于病媒遗传操作的控制策略。我们已经征集了关联制图领域的专家（埃利亚扎·埃斯金博士）和生态数据空间分析领域的专家（丹尼尔·海顿博士），他们将担任顾问，以确保使用最现代和最好的方法来分析数据。

DESCRIPTION (provided by applicant): Sequencing of the genome of Anopheles gambiae s.s., one of the primary mosquito vector of malaria in Africa, has been touted as "...a breakthrough in public health" by providing a means for mapping, selecting and exploiting genes of interest. To date the major focus of such efforts has been on exploring the genetic basis of susceptibility to malaria parasites (Plasmodium sp.) in model systems in the laboratory. These have often not translated well to what is occurring in nature. Indeed, it has become clear that examining vector phenotypes in an ecological context, as they occur in nature, is critical for producing results relevant to malaria epidemiology in real transmission settings. In this application we propose a research program that integrates vector population genomics, ecology and vector behavior with the goal of understanding the determinants of two mosquito behavioral phenotypes crucial to the transmission and control of malaria: (1) host-preference and (2) adult resting behavior. Our approach builds upon a sizeable base of preliminary work in the laboratory which has identified an extensive panel of An. arabiensis SNP markers, and preliminary field work in Tanzania that has identified a range of appropriate sites where sampling methods have been piloted and the behavior of An. arabiensis is known to vary. An. arabiensis mosquitoes will be intensively collected from four villages in the Kilombero Valley of Tanzania during the wet and dry seasons to determine the association between their feeding and resting phenotype and environmental factors that vary temporally and spatially (Aim #1). DNA will be extracted from individual samples and multi-locus SNP genotypes determined from each individual. Genotypes will be organized by phenotype (exophilic vs. endophilic and human fed vs. animal fed) and analyzed to determine SNP allele associations with each phenotype after correcting for population structure and genetic relatedness using the efficient mixed-model association (EMMA) method (Aim #2). Knowledge of the genetic basis of these behavioral changes will be vital for prediction of both possible downstream evolutionary responses to current vector control strategies, and also for the development of novel control strategies that improve the application of currently available vector control methods and/or that are based on vector genetic manipulation. We have enlisted experts in the fields of association mapping (Dr. Eleazar Eskin) and spatial analysis of ecological data (Dr. Daniel Haydon) who will serve as consultants to ensure that the most contemporary and best methods are used for the analysis of data.