Highly finished chromosome-based genome assembly for Anopheles gambiae

高度完成的冈比亚按蚊染色体基因组组装

• 批准号: 8095936
• 负责人: IGOR V SHARAKHOV
• 金额: $ 22.7万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8095936
• 关键词: Achievement; Africa; African; Animal Model; Anopheles Genus; Anopheles gambiae; Biological; Caenorhabditis elegans; Chromosomes; Communicable Diseases; Communities; Competence; Complement; Complex; Confusion; Culicidae; Cytogenetics; DNA; DNA Resequencing; Disease Vectors; Drosophila melanogaster; Ensure; Epidemiology; Equipment; Family; Funding; Gene Expression Profile; Gene Targeting; Genes; Genetic; Genetic Determinism; Genetic Variation; Genome; Genomics; Goals; Haplotypes; Heterochromatin; Hybrids; In Situ Hybridization; Individual; Intervention; Investments; Knowledge; Lasers; Lead; Malaria; Maps; Microdissection; Microscopic; Mining; National Human Genome Research Institute; National Institute of Allergy and Infectious Disease; Phylogenetic Analysis; Population; Public Health; Reading; Regulatory Element; Repetitive Sequence; Research Personnel; Role; Source; Study models; Work; Y Chromosome; base; comparative; comparative genomics; genome sequencing; high throughput technology; improved; next generation; novel strategies; paralogous gene; scaffold; sex; vector; vector control

DESCRIPTION (provided by applicant): The African malaria mosquito Anopheles gambiae, because of its epidemiological importance, was the first disease vector sequenced. In order to perform full genome annotation for An. gambiae, all sequences that have a biological role in this malaria vector must be identified. However, large gaps, incorrect orientation of some scaffolds, and unmapped sequences still pose a serious problem for accurate annotation and functional characterization of the genome. Knowledge of the full complement of mosquito genes, regulatory elements, and repetitive elements is incomplete without information about what lies in those missing sequences. Moreover, the abundance of incorrectly assembled "hybrid" M and S sequences in the current PEST genome assembly leads to the confusion between paralogous genes and genes from different hyplotypes. The assembly of gene-poor, repeat-rich heterochromatic regions is especially fragmented, and no gene from the heterochromatic Y chromosome has been found. The presence of readable polytene chromosomes and the paramount impact of malaria on public health make An. gambiae the best choice as the first vector with a highly finished genome assembly. The major thrust of this R21 project is to develop a high-quality genome assembly and to explore the genetic content of heterochromatin and the Y chromosome of Anopheles gambiae S-form using high- throughput technologies. The availability of equipment for automated in situ hybridization, next-generation sequencing, laser microdissection, and confocal microscopic analysis, as well as the expertise of the PI and Co-PI in cytogenetics and genomics, will ensure successful achievement of the project's goals. Briefly, the project's specific aims are to 1. Close interscaffold gaps in the S-form assembly by high-throughput whole-genome resequencing and targeted sequencing of BAC/fosmid clones. 2. Physically map and orient sequencing scaffolds to the polytene chromosomes. 3. Microdissect, sequence, and characterize the An. gambiae heterochromatin and Y chromosome. This project will greatly improve the current fragmented genome assembly for the An. gambiae S-form. A new genome assembly will enable researchers to work on functional annotation of the most complete sequencing set and to perform more comprehensive comparative genomics studies with other vectors and model organisms. The availability of genes from the Y chromosome will allow researchers to develop sex- specific vector control interventions and conduct phylogenetic analysis of the An. gambiae complex without complications of introgression. The scientific community will be able to access the new assembly from VectorBase for further mining and functional characterization of the An. gambiae genome. PUBLIC HEALTH RELEVANCE: Targeting genes responsible for vector competence is a novel approach for controlling infectious diseases. A full genome annotation for the major African malaria vector Anopheles gambiae will facilitate identification of the epidemiologically important targets. Toward this goal, the proposed project will develop a high-quality genome assembly for Anopheles gambiae using high-throughput technologies.

描述(申请人提供)：非洲疟疾蚊子冈比亚按蚊，由于其流行病学重要性，是第一个测序的病媒。以执行完整的基因组注释。冈比亚，必须识别在该疟疾媒介中具有生物学作用的所有序列。然而，大的缺口，一些支架的错误定位，以及未映射的序列仍然给基因组的准确注释和功能描述带来了严重的问题。如果没有关于这些缺失序列中存在什么的信息，对蚊子基因、调控元件和重复元件的完整补充的知识是不完整的。此外，当前害虫基因组组合中存在大量错误组装的M和S杂交序列，导致并列基因和来自不同双倍型的基因之间的混淆。缺乏基因、富含重复序列的异染色区的组装尤其碎片化，并且没有发现来自异染色质Y染色体的基因。可读多线染色体的存在和疟疾对公共卫生的最大影响造成了。冈比亚是第一个具有高度完成的基因组组装的载体的最佳选择。这项R21计划的主要目的是开发高质量的基因组组件，并利用高通量技术探索冈比亚按蚊S型异染色质和Y染色体的遗传含量。自动化原位杂交、下一代测序、激光显微解剖和共聚焦显微镜分析设备的可用性，以及PI和Co-PI在细胞遗传学和基因组学方面的专业知识，将确保成功实现该项目的目标。简而言之，该项目的具体目标是：1.通过高通量全基因组重测序和对BAC/Fosmid克隆的定向测序，弥合S形式组装中的骨架间隙。2.将测序支架物理定位和定向到多线染色体。3.对听神经进行显微解剖、测序和表征。冈比亚异染色质和Y染色体。该项目将极大地改善目前AN的片段化基因组组装。冈比亚的S形。新的基因组组合将使研究人员能够对最完整的测序集进行功能注释，并与其他载体和模式生物进行更全面的比较基因组学研究。Y染色体基因的可获得性将使研究人员能够开发针对性别的媒介控制干预措施，并对AN进行系统发育分析。冈比亚复合体无渗入并发症。科学界将能够从VectorBase访问新的组件，以进一步挖掘和描述AN的功能。冈比亚亚纲基因组。 公共卫生相关性：针对与媒介能力有关的基因是控制传染病的一种新方法。非洲主要疟疾媒介冈比亚按蚊的全基因组注释将有助于确定流行病学上的重要目标。为了实现这一目标，拟议的项目将使用高通量技术为冈比亚按蚊开发高质量的基因组组装。