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（由申请人提供）：非洲疟疾蚊子对冈比亚的流行病学重要性是第一个测序的疾病载体。为了执行an的完整基因组注释。冈比亚，必须鉴定出在该疟疾载体中具有生物学作用的所有序列。然而，较大的差距，某些支架的不正确方向和未塑造的序列仍然对基因组的准确注释和功能表征提出了一个严重的问题。了解蚊子基因，调节元素和重复元素的完整补充知识是不完整的，而没有有关这些缺失序列中的内容的信息。此外，当前有害生物基因组组装中的不正确组装的“混合” M和S序列会导致寄生虫基因与来自不同流域的基因之间的混淆。基因贫乏的，重复富的异质区域的组装特别分散，没有发现异质Y染色体的基因。可读的多烯染色体的存在和疟疾对公共卫生的最高影响使得。冈比亚是第一个具有高度成品基因组组件的向量的最佳选择。 该R21项目的主要力量是开发高质量的基因组组装，并探索使用高通量技术的异染色质和Anopheles gambiae S-form的Y染色体的遗传含量。用于自动的原位杂交，下一代测序，激光显微解剖和共聚焦显微镜分析以及PI和Co-PI在细胞遗传学和基因组学方面的专业知识的可用性，将确保成功实现项目目标的实现。简而言之，该项目的具体目的是1。通过高通量全基因组重新统计和BAC/FOSMID克隆的靶向测序，S-CORM组装中的施加间差距紧密。 2。在物理上绘制和定向测序支架与多烯染色体。 3。微解答，序列和表征an。冈比亚异染色质和Y染色体。 该项目将大大改善当前AN的零散基因组组件。冈比亚S形式。一个新的基因组组装将使研究人员能够致力于对最完整的测序集的功能注释，并与其他媒介和模型生物进行更全面的比较基因组学研究。 Y染色体的基因的可用性将使研究人员能够开发性别 - 载体控制干预措施，并对AN进行系统发育分析。冈比亚复合物没有并发症的并发症。科学界将能够从VectorBase访问新的大会，以进一步采矿和功能表征。冈比亚基因组。 公共卫生相关性：针对负责向量能力的基因是控制传染病的一种新方法。针对非洲主要疟疾载体小动物冈比亚的全基因组注释将有助于鉴定流行病学上重要的靶标。为了实现这一目标，拟议的项目将使用高通量技术开发针对冈比亚的Anopheles gambiae的高质量基因组组件。