Ecological and genetic determinants of malaria transmitting behaviors in the Afri

描述(申请人提供)：冈比亚按蚊基因组测序是非洲疟疾的主要蚊媒之一，它为绘制、选择和利用感兴趣的基因提供了一种方法，被吹捧为“……公共卫生领域的一项突破”。到目前为止，这些努力的主要焦点一直是探索疟疾寄生虫(疟疾sp.)易感性的遗传基础。在实验室的模型系统中。这些往往没有很好地转化为自然界正在发生的事情。事实上，很明显，在自然界中发生的生态背景下检查媒介表型，对于在真实传播环境中产生与疟疾流行病学相关的结果至关重要。在这项应用中，我们提出了一个整合了媒介种群基因组学、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相当大的前期工作基础上，实验室已经确定了一个广泛的小组。阿拉伯SNP标记，以及坦桑尼亚的初步实地工作，已经确定了一系列试行抽样方法的适当地点和蚊子的行为。已知的阿拉伯人是不同的。一种。将在雨季和旱季从坦桑尼亚基隆贝罗河谷的四个村庄集中采集阿拉伯蚊子，以确定它们的取食和休息表型与在时间和空间上不同的环境因素之间的关联(目标1)。DNA将从个体样本中提取，并从每个个体中确定多个座位的SNP基因类型。基因类型将按表型(外嗜性与内嗜性、人喂养与动物喂养)进行组织，并在使用有效的混合模型关联(EMMA)方法校正种群结构和遗传关联性(目标2)后，分析以确定SNP等位基因与每种表型的关联。这些行为变化的遗传基础的知识对于预测对当前媒介控制策略可能的下游进化反应，以及对于开发新的控制策略，以改进当前可用的媒介控制方法的应用和/或基于媒介基因操作的新的控制策略，将是至关重要的。我们聘请了协会测绘领域的专家(Eleazar Ekin博士)和生态数据空间分析领域的专家(Daniel Haydon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。 公共卫生相关性：在这项申请中，我们提出了一个整合了媒介种群基因组学、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。我们建议研究阿拉伯按蚊的这些特征。冈比亚按蚊(Anopheles冈比亚)S.S.经常被认为是非洲最重要的疟疾媒介，一直是疟疾媒介研究的主要重点。尽管受到了这种关注，但越来越多的证据表明，它不是这个物种，而是它的姐妹物种。在非洲，越来越多的人对疟疾传播负有责任。报告表明，在杀虫剂处理蚊帐(ITN)覆盖率较高的地区，有一种。阿拉伯在竞争中击败了An。冈比亚，并已成为许多地方的优势媒介物种。如果随着大规模的ITN计划在非洲各地铺开，这种现象继续下去，该物种可能成为非洲大陆许多地区唯一具有医学意义的媒介。因此，这种在某种程度上被忽视的媒介的生态学、媒介能力和种群遗传学值得特别关注，为未来的媒介控制情景做准备。蚊子行为的各个方面，包括宿主偏好和休息行为，往往代表着疟疾控制运动的目标。这些行为的变异可能有一个潜在的遗传基础，形成了媒介进化对控制努力的行为抵抗的方式。通过识别和区分寄主偏好和休眠行为变异的环境和遗传决定因素，我们可以就以下方面为防治工作提供信息：何时何地使用它们，目标种群如何反应，这种反应在空间和时间上如何变化，以及如何操纵这种反应来提高药效和管理抗性。

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. PUBLIC HEALTH RELEVANCE: 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. We propose to examine these traits in the mosquito Anopheles arabiensis. Anopheles gambiae s.s. is frequently referred to as the most important vector of malaria in Africa and has been the main focus of malaria vector research. Despite this attention, there is growing evidence that it is not this species, but its sister species An. arabiensis that is increasingly responsible for malaria transmission in Africa. Reports indicate that in areas of high insecticide treated net (ITN) coverage, An. arabiensis outcompetes An. gambiae s.s and has become the dominant vector species in many locations. If this phenomenon continues as large-scale ITN programs are rolled out across Africa, this species could become the only medically relevant vector in many parts of the continent. Consequently the ecology, vectorial competence and population genetics of this somewhat neglected vector merit particular attention in preparation for future vector control scenarios. Aspects of mosquito behavior, including host preference and resting behavior, frequently represent the targets of malaria control campaigns. Variation in these behaviors likely has an underlying genetic basis that forms the means by which vectors evolve behavioral resistance to control endeavors. By identifying and distinguishing environmental and genetic determinants of variation in host preference and resting behavior we can inform control efforts with respect to: where and when they should be applied, how target populations may respond, how this response may vary spatially and in time, and how this response may be manipulated to improve efficacy and manage resistance.