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: 8619578
• 负责人: GREGORY C. LANZARO
• 金额: $ 48.89万
• 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/8619578
• 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; public health relevance; 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.

描述（由申请人提供）：Anopheles Gambiae S.S.的基因组的测序是非洲疟疾的主要蚊子媒介之一，已通过提供一种用于映射，选择和利用感兴趣的基因的方法来吹捧为“ ...公共卫生的突破”。迄今为止，此类努力的主要重点是探索实验室模型系统中对疟疾寄生虫（疟原虫）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。的确，很明显，在生态环境中检查矢量表型在自然界中发生，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。在此应用中，我们提出了一项研究计划，该计划将媒介群体基因组学，生态学和载体行为整合起来，目的是了解两个蚊子行为表型的决定因素，对疟疾的传播和控制至关重要：（1）宿主 - 偏爱和（2）成人休息行为。我们的方法建立在实验室中大量的初步工作的基础上，该实验室已经确定了广泛的面板。坦桑尼亚的Arabiensis SNP标记和初步现场工作，这些标记已经确定了一系列适当的地点，这些地点已被试用，并进行了AN的行为。众所周知，阿拉伯人有所不同。一个。在潮湿和干旱季节，将从坦桑尼亚基洛姆贝罗山谷的四个村庄中进行大量收集阿拉伯蚊子，以确定它们的喂养和静止表型与环境因素之间在时间和空间上变化的环境因素之间的关联（AIM＃1）。 DNA将从单个样本中提取，并从每个个体确定的多级别SNP基因型中提取。基因型将通过表型（卵子与内噬和人喂养与动物饲料）进行组织，并通过使用有效的混合模型关联（EMMA）方法纠正种群结构和遗传相关性后，分析以确定SNP等位基因与每个表型的关联（AIM＃2）。对这些行为变化的遗传基础的了解对于预测对当前向量控制策略的可能下游进化反应以及开发新型控制策略的预测至关重要，从而改善了当前可用的向量控制方法和/或基于媒介遗传操作的应用。我们已经招募了协会映射领域（Eleazar Eskin博士）和生态数据的空间分析（Daniel Haydon博士）的专家，他们将担任顾问，以确保使用最现代和最佳的方法用于数据分析。