Population genetics of transgenes in mosquito vectors

蚊子载体转基因的群体遗传学

• 批准号: 7046918
• 负责人: FRED GOULD
• 金额: $ 31.57万
• 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/7046918
• 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）：昆虫菌株已经过基因设计，以减少繁殖能力和无法传播引起疾病的病原体的能力。具有这种特征的昆虫预计不会通过自然选择的直接作用来代替天然昆虫的基因型，因此有必要开发出遗传驱动机制，以将这些转基因迫使这些转基因迫使本地昆虫种群。已经讨论了许多使用特定驱动机制的潜在策略，并开发了初步的人口遗传模型来评估某些策略的可行性。这些评估中存在许多差距。拟议的研究将开发一个全面的建模框架，该框架可用于确定最有可能成功抑制特定地区特定昆虫传播疾病的转基因方法。主要重点是建立媒介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结合使用。第一个模型将旨在拟合埃及伊德（Aedes Aegypti）和登革热病毒（DV）的生物学。从以前的研究和正在进行的研究中获得了许多相关生物学参数的估计。其他参数将从提议的实验中估算，这些实验将衡量预期与转基因插入有关的适应性成本以及负载转座子的基因组运动的模式。将要检查的特定转基因操作是：1）插入条件致死等位基因的插入，2）插入女性特异性致死性等位基因的插入3）工程不足，4）插入负载的自主转座子，5）带有转基因沃尔巴奇菌株的感染。使用新型转基因操作的潜力将使用更一般的模型进行检查。建模工作的结果将基于当前的生物学数据预测，DV抑制策略有望在特定的环境条件下成功。结果还将表明应将未来的经验研究工作集中在何处，以获得对AE关键生物学参数的更精确和准确的估计。埃及。 将举行跨学科研讨会，以确保开发的最终模型框架足够灵活，可以被疟疾和其他昆虫传播疾病的研究人员使用。模型的用户友好形式以及可访问的手册将被开发并放置在互联网上。