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: 10192080
• 负责人: IGOR V SHARAKHOV
• 金额: $ 24.56万
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192080
• 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; structural genomics; 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.

项目总结/摘要 非洲疟疾蚊子冈比亚按蚊，因为它在流行病学上的重要性， 2002年完成了基因组测序。从那时起，PEST菌株组件仍然是唯一的 这是非洲疟疾主要传播媒介的染色体水平基因组参考。虽然这个大会 近20年来一直是疟疾蚊子功能和种群基因组研究的主力， 它现在未能提供尽可能高质量的分析，因为它是惊人的不完美的现代 标准该组装具有严重的缺陷，例如大部分未映射的重叠群、测序和测序。 物理间隙，一些支架的不正确顺序和方向，以及衍生自 姐妹物种An.猫猴。此外，PEST菌株的An.冈比亚已不复存在，现有的 组装不能通过额外的测序来验证或改进。因此，一个完整的注释和 一个准确的功能表征的一个。冈比亚的基因组不能进行。此外，缺乏 可靠的参考是人口基因组学研究的主要障碍，特别是对那些处理 基因组结构变异。长期以来，测序的高成本和基因组测序的绝对困难 组装使得蚊子基因组的重大改进受到限制。新型长读测序 技术和创新的支架方法现在允许开发从头染色体水平的基因组 以合理的成本生产上级质量的组件。此外，多线染色体的可用性确保了高- 高分辨率基因组作图。冈比亚。这个R21项目的主要目标是开发一个染色体水平的 基因组组装和探索结构基因组变异的An.冈比亚情结。这一及时 该项目将满足非洲主要疟疾病媒对新的高成品基因组组装的需求 基于PI和Co-I的适当创新工具和专业知识。简而言之，该项目的具体目标 目的是（1）获得An的连续基因组组装。gambiae使用Oxford Nanopore，Illumina测序， 和染色体规模的Hi-C支架;（2）对获得的组装体进行测序，并构建高分辨率的 物理基因组图谱。（3）用荧光原位杂交技术对冈比亚红细胞进行结构鉴定 基因组变异在An.冈比亚情结。一个新的染色体水平的基因组组装。冈比亚按蚊 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口 疟疾蚊子的分析异染色质序列的更完整的组装将提高我们的 了解基因组“暗物质”，并将刺激这种疾病载体的表观基因组研究。的 科学界将可以免费访问VEuPathDB和NCBI的新组件。