Population genetics of transgenes in mosquito vectors

蚊子载体转基因的群体遗传学

• 批准号: 6888550
• 负责人: FRED GOULD
• 金额: $ 28.8万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6888550
• 关键词: Aedes; Internet; Rickettsia; alleles; animal population genetics; arthropod borne communicable disease; arthropod genetics; arthropod nonpollutant control; biological models; biotechnology; communicable disease control; computer simulation; dengue; dengue virus; disease vectors; gene environment interaction; genetic manipulation; genetic models; genetically modified animals; green fluorescent proteins; lethal genes; model design /development; polymerase chain reaction; transfection; transfection /expression vector; transposon /insertion element; workshop

DESCRIPTION (provided by the applicant): Insect strains have been genetically engineered for decreased capacity to reproduce and for inability to transmit disease-causing pathogens. Insects with such traits are not expected to replace native insect genotypes through the direct action of natural selection so there is a need to develop genetic drive mechanisms that will force these transgenes into native insect populations. A number of potential strategies for using specific drive mechanisms have been discussed, and preliminary population genetic models have been developed to assess the feasibility of certain strategies. There are numerous gaps in these assessments. The proposed research will develop a comprehensive modeling framework that can be used in determining the transgenic approaches that are most likely to successfully suppress specific insect-borne diseases in specific regions. A major focus will be the building of a spatially explicit stochastic model of vector population dynamics and genetics. This model will be coupled to models of disease epidemiology. The first model will be designed to fit the biology of Aedes aegypti and dengue virus (DV). Estimates of many relevant biological parameters are available from previous and ongoing research. Other parameters will be estimated from proposed experiments that will measure the fitness costs expected to be associated with insertion of transgenes, and the pattern of intra-genomic movement of loaded transposons. Specific transgenic manipulations that will be examined are: 1) insertion of conditional lethal alleles, 2) insertion of female-specific lethality alleles 3) engineered underdominance, 4) insertion of loaded autonomous transposons, 5) infection with transgenic Wolbachia strains. The potential for using novel transgenic manipulations will be examined with more general models. Results of the modeling work will predict, based on current biological data, which DV suppression strategies are expected to succeed under specific environmental conditions. The results will also indicate where future empirical research efforts should be focused to gain more precise and accurate estimates of critical biological parameters for Ae. aegypti. Interdisciplinary workshops will be held to ensure that the final model framework developed is flexible enough to be used by researchers working with malaria and other insect-borne diseases. A user-friendly form of the models as well as an accessible manual will be developed and placed on the internet.

描述（由申请人提供）：昆虫品系经过基因工程改造，降低了繁殖能力，并且无法传播致病病原体。具有这些性状的昆虫预计不会通过自然选择的直接作用取代本地昆虫基因型，因此需要开发遗传驱动机制，迫使这些转基因进入本地昆虫种群。已经讨论了使用特定驱动机制的许多潜在策略，并且已经开发了初步的群体遗传模型来评估某些策略的可行性。这些评估存在许多差距。拟议的研究将开发一个全面的建模框架，可用于确定最有可能成功抑制特定地区特定虫媒疾病的转基因方法。主要重点是建立矢量种群动态和遗传学的空间显式随机模型。该模型将与疾病流行病学模型相结合。第一个模型的设计将适合埃及伊蚊和登革热病毒（DV）的生物学特性。许多相关生物参数的估计可以从之前和正在进行的研究中获得。其他参数将从拟议的实验中估计，这些实验将测量与转基因插入相关的适应性成本，以及加载转座子的基因组内运动模式。将检查的具体转基因操作是：1）插入条件致死等位基因，2）插入雌性特异性致死等位基因，3）工程改造的弱优势，4）插入加载的自主转座子，5）用转基因沃尔巴克氏体菌株感染。使用新型转基因操作的潜力将通过更通用的模型进行检验。建模工作的结果将根据当前的生物学数据预测哪些 DV 抑制策略有望在特定环境条件下取得成功。研究结果还将表明未来的实证研究工作应集中在哪里，以获得对白纹伊菌关键生物学参数更精确和准确的估计。埃及伊蚊。 将举办跨学科研讨会，以确保最终开发的模型框架足够灵活，可供研究疟疾和其他虫媒疾病的研究人员使用。将开发用户友好的模型形式以及易于访问的手册，并将其放置在互联网上。