Ecological and genetic determinants of malaria transmitting behaviors in the Afri

非洲疟疾传播行为的生态和遗传决定因素

• 批准号: 8107426
• 负责人: GREGORY C. LANZARO
• 金额: $ 58.91万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-03 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8107426
• 关键词: Adult; Africa; African; Alleles; Animal Feed; Animals; Anopheles Genus; Anopheles gambiae; Area; Attention; Behavior; Behavioral; Biological; Biological Models; Blood; Climate; Competence; Culicidae; DNA; Data; Data Analyses; Development; Ecology; Ensure; Environmental Risk Factor; Epidemiology; Exhibits; Future; Genes; Genetic; Genetic Determinism; Genetic Markers; Genomics; Genotype; Goals; Habitats; Health; Household; Housing; Human; Humidity; Individual; Insecticides; Institutes; Intervention; Investigation; Knowledge; Laboratories; Livestock; Location; Malaria; Maps; Measures; Methods; Modeling; Nature; Parasites; Phenotype; Plasmodium; Population; Population Genetics; Predisposition; Preparation; Public Health; Reaction Time; Reporting; Research; Residual state; Resistance; Rest; Risk; Role; SNP genotyping; Sampling; Seasons; Sister; Site; Source; Structure; Tanzania; Target Populations; Temperature; Translating; Variant; Work; base; experience; exposed human population; feeding; genetic manipulation; genome sequencing; improved; innovation; interdisciplinary approach; interest; knowledge base; neglect; novel; population genetic structure; preference; programs; response; success; trait; transmission process; vector; vector control; vector mosquito

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.

描述（由申请人提供）：冈比亚按蚊（Anopheles gambiae s.s.）是非洲疟疾的主要蚊媒之一，其基因组测序通过提供一种绘制、选择和分析的方法而被誉为“……公共卫生领域的突破”。利用感兴趣的基因。迄今为止，此类工作的主要重点是在实验室模型系统中探索疟疾寄生虫（疟原虫属）易感性的遗传基础。这些通常不能很好地转化为自然界中发生的事情。事实上，很明显，在生态背景下检查媒介表型（就像它们在自然界中发生的那样）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，我们提出了一项研究计划，将媒介群体基因组学、生态学和媒介行为相结合，旨在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大量的前期工作基础上，该工作已经确定了广泛的 An 小组。 arabiensis SNP 标记，以及在坦桑尼亚的初步实地工作，确定了一系列适当的地点，在这些地点试点了采样方法和 An. arabiensis SNP 的行为。已知 arabiensis 存在差异。一个。将在雨季和旱季期间从坦桑尼亚 Kilombero 山谷的四个村庄集中收集阿拉伯蚊子，以确定它们的摄食和休息表型与时空变化的环境因素之间的关联（目标＃1）。将从个体样本中提取 DNA，并确定每个个体的多位点 SNP 基因型。基因型将按表型（外嗜性与内嗜性以及人类喂养与动物喂养）进行组织，并在使用高效混合模型关联 (EMMA) 方法校正种群结构和遗传相关性后进行分析，以确定 SNP 等位基因与每个表型的关联（目标＃2）。了解这些行为变化的遗传基础对于预测对当前病媒控制策略可能的下游进化反应至关重要，对于开发新的控制策略以改善现有病媒控制方法的应用和/或基于载体遗传操作。我们聘请了关联绘图领域的专家（Eleazar Eskin 博士）和生态数据空间分析领域的专家（Daniel Haydon 博士）作为顾问，以确保使用最现代、最好的方法来分析数据。 公共卫生相关性：在本申请中，我们提出了一项研究计划，将媒介群体基因组学、生态学和媒介行为相结合，旨在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)成人休息行为。我们建议检查阿拉伯按蚊的这些特征。冈比亚按蚊 s.s.经常被认为是非洲最重要的疟疾媒介，并且一直是疟疾媒介研究的主要焦点。尽管受到如此关注，越来越多的证据表明它不是这个物种，而是它的姐妹物种An。阿拉伯疟原虫对非洲疟疾的传播负有越来越大的责任。报告表明，在杀虫剂处理网 (ITN) 覆盖率较高的地区，An. arabiensis 战胜了 An.冈比亚 s.s 并已成为许多地方的主要媒介物种。如果随着大规模杀虫剂蚊帐计划在非洲各地展开，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的医学相关媒介。因此，在为未来的病媒控制方案做准备时，这种有点被忽视的病媒的生态学、病媒能力和群体遗传学值得特别关注。蚊子行为的各个方面，包括宿主偏好和休息行为，经常代表疟疾控制运动的目标。这些行为的变异可能具有潜在的遗传基础，形成了载体进化出对控制努力的行为抵抗力的手段。通过识别和区分宿主偏好和休息行为变化的环境和遗传决定因素，我们可以为控制工作提供以下方面的信息：应在何时何地应用它们，目标人群可能如何反应，这种反应如何在空间和时间上变化，以及如何操纵这种反应来提高功效和管理耐药性。