Chromosomal rearrangements in arboviral vector Aedes aegypti

虫媒病毒载体埃及伊蚊的染色体重排

• 批准号: 9974917
• 负责人: Maria Sharakhova
• 金额: $ 22.76万
• 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: 2020-02-07 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9974917
• 关键词: Aedes; Aedes aegypti genome; Anopheles Genus; Arbovirus Infections; Behavioral; Biological Assay; Brazil; Chromosomal Rearrangement; Chromosome Mapping; Chromosome inversion; Chromosomes; Color; Country; Culicidae; Data; Dengue; Dengue Fever; Development; Disease Outbreaks; Environment; Epidemic; Epidemiologic Factors; Epidemiology; Fluorescent in Situ Hybridization; Future; Genetic; Genetic study; Genome; Genome Mappings; Genomics; Goals; Health; Human; Human Genome; Infection; Knowledge; Length; Location; Maintenance; Medical; Methods; Microcephaly; Mosquito Control; Mosquito-borne infectious disease; Newborn Infant; Phenotype; Population; Production; Quantitative Trait Loci; Research Personnel; Rural; Senegal; Structure; Technology; Testing; Uganda; Vaccines; Validation; Variant; Vector-transmitted infectious disease; base; disease transmission; disorder prevention; experience; experimental study; forest; genome sequencing; improved; innovation; nanopore; pathogen; physical mapping; preference; prevent; scaffold; tool; trait; vector; vector control; virtual; zika fever

PROJECT SUMMARY Aedes aegypti transmits several arboviral diseases, including dengue and Zika fever, which threaten virtually half of the world’s population. Two subspecies, Ae. aegypti aegypti (Aaa) and Ae. aegypti formosus (Aaf), have been described based on their body coloration. These two subspecies differ remarkably from each other in their worldwide distribution, association with humans, and ability to transmit pathogens. In Anopheles populations, polymorphic inversions are often responsible for epidemiologically important phenotypes but our knowledge about chromosomal rearrangements in Aedes populations is scarce. So far, only two chromosomal inversions have been directly observed in chromosomes of Ae. aegypti from Senegal. Based on our preliminary data, we hypothesize that chromosomal inversions are abundant in Ae. aegypti and are involved in the establishment and maintenance of genomic and phenotypic divergence in natural populations of this mosquito. In this study, we will take advantage of a dramatically improved, fully re-annotated genome assembly for Ae. aegypti and employ the Hi-C approach along with Oxford Nanopore Technology (ONT) sequencing to characterize chromosomal rearrangements. [The primary goal of this R21 proposal is to identify chromosomal rearrangements in aedine mosquitoes]. Toward this end, we propose three specific aims: 1) characterize chromosomal rearrangements in 16 strains of Aaa and Aaf from various worldwide populations using the Hi-C approach; 2) develop a high-quality de novo genome assembly for the Aaf Uganda strain using advanced genome technologies; and 3) develop PCR and FISH-based approaches for identification of the 3p2 chromosomal inversion, which is potentially of medical importance. The innovative strategies of using Hi-C analysis and ONT sequencing will make possible the discovery of chromosomal inversions in Ae. aegypti and will stimulate future genetic studies aimed at preventing mosquito-borne disease transmission.

项目概要 埃及伊蚊传播多种虫媒病毒性疾病，包括登革热和寨卡热，这对人类造成威胁 埃及伊蚊 (Aaa) 和台湾伊蚊 (Aegypti formosus) 几乎占世界人口的一半。 (Aaf)，根据它们的身体颜色进行了描述。 其他方面包括它们的全球分布、与人类的关联以及传播病原体的能力。 在人群中，多态性倒置通常是流行病学上重要的表型的原因，但我们的 迄今为止，关于伊蚊种群染色体重排的知识很少。 根据我们的研究，在埃及伊蚊的染色体中直接观察到了倒位。 根据初步数据，我们推测埃及伊蚊中存在丰富的染色体倒位，并参与其中。 自然群体中基因组和表型差异的建立和维持 在这项研究中，我们将利用显着改进的、完全重新注释的基因组。 埃及伊蚊的组装，并采用 Hi-C 方法和牛津纳米孔技术 (ONT) 测序来表征染色体重排[该 R21 提案的主要目标是 鉴定蚊子的染色体重排]为此，我们提出了三种具体的方案。 目标：1) 表征来自不同来源的 16 个 Aaa 和 Aaf 菌株的染色体重排 使用 Hi-C 方法对全世界人群进行开发；2) 开发高质量的从头基因组组装； 使用先进的基因组技术针对 Aaf 乌干达菌株；3) 开发基于 PCR 和 FISH 的技术 鉴定 3p2 染色体倒位的方法，这具有潜在的医学意义 使用 Hi-C 分析和 ONT 测序的创新策略将使这一点成为可能。 埃及伊蚊染色体倒位的发现将刺激未来的遗传学研究 防止蚊媒疾病传播。