Sex ratio distortion in Aedes aegypti

埃及伊蚊性别比例扭曲

• 批准号: 10264907
• 负责人: Zhijian Jake Tu
• 金额: $ 68.63万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264907
• 关键词: Address; Aedes; Anopheles gambiae; Area; Biological; CRISPR/Cas technology; Cells; Chikungunya virus; Chromatin; Chromosome 1; Chromosome Breakage; Chromosome Pairing; Chromosomes; Culex (Genus); Culicidae; Dengue; Dengue Vaccine; Dengue Virus; Dengvaxia; Disease Outbreaks; Economics; Equilibrium; Female; Future; Genes; Genetic Transcription; Geography; Haplotypes; Incidence; Insecticide Resistance; Laboratories; Link; Male Sterility; Measures; Meiosis; Methods; Minor Lymphocyte Stimulatory Loci; Mitosis; Modeling; Molecular; Mosquito Control; Mosquito-borne infectious disease; Myeloma Proteins; Names; Population; Population Growth; Population Replacements; Prevention; Probability; Property; RNA-Binding Proteins; Research; Resistance; Sex Bias; Sex Chromosomes; Sex Differences; Sex Ratio; Site; Specificity; Split Genes; Surveys; System; Testing; Time; Transgenes; Transgenic Organisms; Wolbachia; Wood material; X Chromosome; Y Chromosome; ZIKA; Zika Virus; active control; chikungunya; cost; disease transmission; disorder control; fitness; genetic approach; genetic manipulation; improved; innovation; innovative technologies; insight; male; novel; programs; promoter; prototype; sex; sperm cell; tool; transgene expression; transmission process; vector; vector control; vector management strategies

Project Summary Aedes aegypti is a major vector of dengue, chikungunya, and Zika viruses. The global incidence of dengue has increased dramatically in recent decades. The first dengue vaccine, Dengvaxia®, is recommended for a very limited population. Current prevention depends mainly on effective vector control, which is hindered by increasing insecticide-resistance. Novel genetic strategies for vector control are actively explored, including both population suppression and population replacement. Recent field releases of either transgenic and Wolbachia-infected sterile male mosquitoes show promising results for suppressing Aedes populations in areas of modest size. Given the biological, geographical, economic and cultural complexity facing global mosquito-borne infectious disease control programs, diverse measures that can be integrated to address various challenges are urgently needed. Female to male sex ratio distortion is an attractive concept for developing new control measures, as females are responsible for disease transmission and population growth. Aedes and Culex mosquitoes contain homomorphic sex- determining chromosomes and maleness is conferred by a dominant male-determining factor (M factor) within an M locus that is on one of a pair of chromosome 1. Male-biased sex-ratio distortion occurs in natural populations in Ae. aegypti, which is associated with m-chromosome breakage during meiosis at a few sites. The Distorter locus is linked to the M-locus on the M-chromosome, conferring a meiotic drive as it increases the probability of its own inheritance. We recently discovered the M factor, an RNA-binding protein named Nix and identified the M and m locus in Ae. aegypti. By analysing male and female Illumina reads across a few strains, we found a number of m-specific repeats that can be targeted for breakage by CRISPR/cas9 during male meiosis, potentially leading to a male-biased sex ratio distortion. We will pursue the following specific aims: 1) Systematically characterize components to develop m-shredders. Research performed here will also improve our understanding of the male germline and the homomorphic sex chromosomes and facilitate any future genetic manipulations involving the male germline. 2) Develop m-shredder lines with various degrees of M-linkage to optimize effective population suppression. 3) Model various applications of m-shredders in population suppression and transgene recall. In summary, innovative technologies will be used to gain fundamental insights into male germline expression and the differentiation of the homomorphic sex chromosomes of Ae. aegypti. m-shredders with various levels of efficiency and transmissibility will be developed and modelled for population suppression and transgene recall, expanding the tool box for integrated vector management. 1

项目摘要 埃及埃及是登革热，基孔肯亚和Zika病毒的主要媒介。全球事件的 近几十年来，登革热大大增加了。第一种登革热疫苗Dengvaxia®是 推荐给非常有限的人口。当前的预防主要取决于有效的向量控制， 增加杀虫剂的抗性会阻碍。媒介控制的新型遗传策略是 积极探索，包括抑制人口和人口替代。最近的领域 释放的转基因和沃尔巴氏菌的无菌男性蚊子显示出有希望的结果 在适度的区域中抑制艾德斯种群。鉴于生物学，地理，经济 以及全球蚊子传染病控制计划面临的文化复杂性，潜水员 迫切需要采取可以集成以应对各种挑战的措施。女性到男性 比率失真是制定新的控制措施的有吸引力的概念，因为女性是负责任的 用于疾病传播和人口增长。艾德斯和库尔克斯蚊子包含同态性别 - 确定染色体和男性性是由主要的男性决定因素（M因子）赋予的 在一个位于一对染色体1之一上的M基因座中。男性偏见性比率发生发生在 AE中的自然种群。埃及，与减数分裂期间的M染色体破裂有关 一些网站。 Tixorter基因座与M-chromosom体上的M-Locus相关 随着它增加了自身继承的可能性。我们最近发现了M因子，RNA结合 蛋白质名为Nix，并在AE中鉴定了M和M基因座。埃及。通过分析男性和女性光明 读取几种菌株，我们发现了许多M特异性重复序列，这些重复可以针对破裂 在男性减数分裂过程中，由CRISPR/CAS9通过，可能导致男性偏见的性别比失真。我们将 追求以下特定目的：1）系统地表征开发M轴向的组件。 这里进行的研究还将提高我们对男性种系和同态的理解 性染色体和最喜欢的任何未来遗传操作涉及男性种系。 2）发展 具有不同程度的M线路的M挡板线以优化有效的种群抑制。 3） 模拟M轴德在种群抑制和转化召回中的各种应用。总之， 创新技术将用于获得对男性种系表达的基本见解和 AE的同态性别染色体的分化。埃及。 M-shredders具有不同级别的 效率和传播性将被开发和建模，以抑制人群和转化 回想一下，扩展用于集成向量管理的工具框。 1