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 埃及伊蚊是登革热、基孔肯雅热和寨卡病毒的主要传播媒介。的全球发病率 登革热在近几十年来急剧增加。第一种登革热疫苗Dengvaxia®， 推荐给非常有限的人群。目前的预防主要依靠有效的病媒控制， 这受到增加的耐腐蚀性的阻碍。用于病媒控制的新型遗传策略是 积极探索，包括人口抑制和人口替代。最近领域 释放转基因和感染沃尔巴克氏体的不育雄性蚊子显示出有希望的结果， 在中等规模的地区抑制伊蚊种群。考虑到生物学、地理学、经济学 全球蚊媒传染病控制计划面临的文化复杂性， 迫切需要采取能够综合处理各种挑战的措施。女变男 比例失真是一个有吸引力的概念，为发展新的控制措施，因为女性负责 疾病传播和人口增长。伊蚊和库蚊具有同形性- 决定染色体和雄性的是一个显性的雄性决定因子（M因子） 在一对1号染色体之一上的M基因座内。男性偏好的性别比例扭曲发生在 自然种群在Ae。埃及伊蚊，这与减数分裂过程中的m染色体断裂有关， 几个网站。Distorter基因座与M染色体上的M基因座连锁，赋予减数分裂驱动力 因为它增加了自身遗传的可能性。我们最近发现了M因子， 蛋白命名为Nix，并确定了M和m基因座在Ae。埃及人。通过分析男女Illumina 在几个菌株中的读数，我们发现了许多可以被靶向断裂的m特异性重复序列， 在雄性减数分裂期间通过CRISPR/cas9，可能导致雄性偏见的性别比例扭曲。我们将 追求以下具体目标：1）系统地表征部件以开发m-粉碎机。 在这里进行的研究也将提高我们对雄性生殖系和同形生殖系的理解。 性染色体，并促进任何未来的基因操纵涉及男性生殖系。2)发展 具有不同程度的M-连锁的m-粉碎线，以优化有效的群体抑制。第三章 模拟m-shredders在群体抑制和转基因回忆中的各种应用。总的来说， 创新技术将用于获得对雄性生殖系表达的基本见解， Ae.的同形性染色体的分化。埃及人。m-粉碎机与各种水平的 效率和可传递性将被开发和建模，用于群体抑制和转基因 召回，扩大综合病媒管理工具箱。 1