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.

项目摘要 埃及伊蚊传播几种虫媒病毒疾病，包括登革热和寨卡热， 几乎占世界人口的一半两个亚种，Ae.埃及伊蚊Aegypti aegypti（Aaa）和埃及伊蚊Ae.台湾埃及 (Aaf)，已经基于它们的身体颜色进行了描述。这两个亚种明显不同， 其他的是它们在世界范围内的分布，与人类的联系，以及传播病原体的能力。按蚊 多态倒位通常是流行病学上重要的表型，但我们的研究表明， 关于伊蚊种群染色体重排的知识很少。到目前为止，只有两个染色体 在山羊草染色体中直接观察到倒位现象。来自塞内加尔的埃及人基于我们 初步数据，我们假设染色体倒位是丰富的Ae。埃及人， 建立和维持自然群体的基因组和表型差异， 蚊子在这项研究中，我们将利用一个显着改进的，完全重新注释的基因组， 组装Ae。埃及和采用Hi-C方法沿着与牛津纳米孔技术（ONT） 测序以表征染色体重排。[The R21提案的主要目标是 鉴定伊蚊染色体重排]。为此，我们提出三个具体的建议。 目的：1）研究16株来自不同地区的Aaa和Aaf菌株的染色体重排， 使用Hi-C方法的全球人群; 2）开发高质量的从头基因组组装 Aaf乌干达菌株使用先进的基因组技术;和3）开发基于PCR和FISH的 方法鉴定3 p2染色体倒位，这是潜在的医疗 重要性使用Hi-C分析和ONT测序的创新策略将使 发现Ae.染色体倒位并将促进未来的基因研究， 预防蚊媒疾病传播。