A chromosome-level genome assembly for the major African malaria vector Anopheles gambiae

主要非洲疟疾载体冈比亚按蚊的染色体水平基因组组装

• 批准号: 10343852
• 负责人: IGOR V SHARAKHOV
• 金额: $ 19.03万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-05 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10343852
• 关键词: Africa South of the Sahara; African; Anopheles Genus; Anopheles gambiae; Beds; COVID-19; Centromere; Cessation of life; Chromosome inversion; Chromosomes; Communities; Complex; Culicidae; Cytogenetics; Cytology; DNA Sequence Rearrangement; Data; Disease Vectors; Drosophila genus; Ecology; Ensure; Epidemiology; Epigenetic Process; Fluorescent in Situ Hybridization; Funding; Gene Targeting; Genetic; Genome; Genome Mappings; Genomic approach; Genomics; Goals; Haplotypes; Heterochromatin; Hi-C; Insecticide Resistance; Insecticides; Link; Malaria; Maps; Methods; Minor; Modernization; Molecular; Outcome; Physical Chromosome Mapping; Population; Population Analysis; Public Health; Research; Research Personnel; Residual state; Resolution; Siblings; Sister; Technology; Testing; Time; Update; Variant; Work; X Chromosome; base; chromosome conformation capture; comparative genomics; contig; cost; cost effective; dark matter; epigenomics; genomic variation; improved; innovation; malaria mosquito; nanopore; novel; physical mapping; prevent; reference genome; scaffold; success; telomere; tool; vector; vector control; welfare

Project Summary/Abstract The African malaria mosquito Anopheles gambiae, because of its epidemiological importance, was the first disease vector, with a genome sequenced in 2002. Since then the PEST strain assembly remains the only available chromosome-level genome reference for this major African malaria vector. Although this assembly has been the workhorse for functional and population genomic studies of malaria mosquitoes for almost two decades, it is now failing to deliver the highest possible quality of the analyses as it is staggeringly imperfect by the modern standards. The assembly has serious deficiencies such as a large portion of unmapped contigs, sequencing and physical gaps, incorrect order and orientation of some scaffolds, and the presence of haplotypes derived from the sister species An. coluzzii. Moreover, the PEST strain of An. gambiae is no longer available and the existing assembly cannot be validated or improved with additional sequencing. As a result, a complete annotation and an accurate functional characterization of the An. gambiae genome cannot be performed. Also, the lack of a reliable reference represents a major impediment to population genomics studies, especially to those dealing with structural genomic variations. For a long time, the high cost of sequencing and the sheer difficulty of genome assembly has made major improvements of the mosquito genome prohibitive. Novel long-read sequencing technologies and innovative scaffolding approaches now allow developing de novo chromosome-level genome assemblies of superior quality at a reasonable cost. Also, the availability of polytene chromosomes ensures high- resolution genome mapping in An. gambiae. The main goal of this R21 project is to develop a chromosome-level genome assembly and to explore the structural genomic variations in the An. gambiae complex. This timely project will meet the demand for a new highly-finished genome assembly for the major African malaria vector based on the appropriate innovative tools and expertise of the PI and Co-I. Briefly, the project’s specific aims are to (1) Obtain a contiguous genome assembly for An. gambiae using Oxford Nanopore, Illumina sequencing, and chromosome-scale Hi-C scaffolding; (2) Validate the obtained assembly and construct a high-resolution physical genome map for An. gambiae using fluorescence in situ hybridization; (3) Characterize structural genomic variations in the An. gambiae complex. A new chromosome-level genome assembly for An. gambiae will transform research as it will allow the most complete functional annotation and the most detailed population analysis of malaria mosquitoes. The more complete assembly of heterochromatic sequences will improve our understanding of the genomic “dark matter” and will stimulate epigenomic studies of this disease vector. The scientific community will have free access to the new assembly from VEuPathDB and NCBI.

项目摘要/摘要 非洲疟疾蚊子巨人冈比亚（Gambiae）由于其流行病的重要性，是第一个 疾病载体，在2002年对基因组进行了测序。此后，害虫菌株组装仍然是唯一的 该主要非洲疟疾载体的可用染色体水平基因组参考。虽然这个大会有 一直是疟疾蚊子功能和人口基因组研究的主力，已有近二十年了， 现在，它无法提供最高的分析质量，因为它是现代的不完美的 标准。组件具有严重的缺陷，例如大部分未塑造的重叠群，测序和 某些脚手架的物理间隙，错误的顺序和方向 姊妹物种coluzzii。此外，An的害虫菌株。冈比亚不再可用，现有 通过其他测序无法验证或改进组件。结果，完整的注释和 AN的准确功能表征。冈比亚基因组不能进行。另外，缺乏 可靠的参考代表了人群基因组学研究的主要障碍，尤其是对交易的人 结构性基因组变异。很长一段时间以来，测序的高成本和基因组的纯粹难度 组装已对禁止的蚊子基因组进行了重大改进。新颖的长阅读测序 技术和创新的脚手架方法现在允许开发从头染色体水平的基因组 质量卓越的组装，成本合理。此外，多烯染色体的可用性可确保高 分辨率基因组映射。冈比亚。这个R21项目的主要目标是开发染色体级别 基因组组装并探索AN中的结构基因组变异。冈比亚综合体。这个及时 项目将满足对主要非洲疟疾媒介的新高度制定基因组组件的需求 基于PI和Co-I的适当创新工具和专业知识。简而言之，该项目的具体目的 要（1）获得An的连续基因组组件。冈比亚使用牛津纳米孔，光明测序， 和染色体规模的Hi-C脚手架； （2）验证所获得的组装并构建高分辨率 An的物理基因组图。冈比亚使用荧光原位杂交； （3）表征结构 an的基因组变异。冈比亚综合体。一个新的染色体级基因组组件。冈比亚 将改变研究，因为它将允许最完整的功能注释和最详细的人群 分析疟疾蚊子。杂色序列的更完整的组装将改善我们的 了解基因组“暗物质”，并将刺激该疾病载体的表观基因组研究。这 科学界将免费访问VeupathDB和NCBI的新大会。