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.

项目概要/摘要 非洲疟疾蚊子冈比亚按蚊因其流行病学重要性而成为第一个疟疾蚊子。 疾病载体，其基因组测序于 2002 年。从那时起，PEST 菌株组装仍然是唯一的 尽管这种组装有这种主要非洲疟疾载体的可用染色体水平基因组参考。 近二十年来一直是疟疾蚊子功能和群体基因组研究的主力， 它现在无法提供尽可能高的分析质量，因为它与现代技术相比极其不完美。 该组装存在严重缺陷，例如大部分未映射的重叠群、测序和 物理间隙、某些支架的顺序和方向不正确，以及衍生自的单倍型的存在 此外，冈比亚 An. coluzzii 的 PEST 菌株已不再可用。 无法通过额外的测序来验证或改进组装，因此无法获得完整的注释和结果。 此外，无法对冈比亚按蚊基因组进行准确的功能表征。 可靠的参考文献是群体基因组学研究的主要障碍，特别是对于那些从事研究的人来说 长期以来，测序成本高昂，基因组研究难度极大。 组装使得蚊子基因组的重大改进令人望而却步。 技术和创新的支架方法现在允许从头开发染色体水平基因组 此外，多线染色体的可用性确保了高品质的组装。 冈比亚按蚊的分辨率基因组图谱 该 R21 项目的主要目标是开发染色体水平的基因组图谱。 基因组组装并探索冈比亚按蚊复合体的结构基因组变异。 该项目将满足非洲主要疟疾病媒对新的高度完成的基因组组装的需求 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。 (1) 使用 Oxford Nanopore、Illumina 测序获得冈比亚按蚊的连续基因组组装， (2) 验证获得的组装体并构建高分辨率 使用荧光原位杂交绘制冈比亚按蚊的物理基因组图谱； (3) 表征结构； 冈比亚按蚊复合体的基因组变异。 将改变研究，因为它将允许最完整的功能注释和最详细的群体 疟疾蚊子的更完整的异染色质序列组装将改善我们的研究。 对基因组“暗物质”的理解并将促进对该疾病载体的表观基因组研究。 科学界将可以免费访问 VEuPathDB 和 NCBI 的新程序集。