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

基本信息

批准号：
8227943
负责人：
IGOR V SHARAKHOV
金额：
$ 19.29万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8227943
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 public health relevance scaffold sex vector vector control

项目摘要

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）：非洲疟疾蚊子冈比亚按蚊由于其流行病学重要性，是第一个被测序的疾病媒介。为了对An进行全基因组注释。冈比亚，必须鉴定在该疟疾载体中具有生物学作用的所有序列。然而，大的间隙、一些支架的错误方向以及未映射的序列仍然对基因组的准确注释和功能表征构成严重问题。如果不了解这些缺失序列中的内容，对蚊子基因、调控元件和重复元件的完整了解是不完整的。此外，当前 PEST 基因组组装中大量错误组装的“杂合”M 和 S 序列导致旁系同源基因和来自不同亚型的基因之间的混淆。基因贫乏、重复丰富的异染色质区域的组装尤其分散，并且尚未发现来自异染色质 Y 染色体的基因。可读多线染色体的存在以及疟疾对公共健康的重大影响使得安。冈比亚是第一个具有高度完成的基因组组装载体的最佳选择。 R21项目的主要目标是开发高质量的基因组组装，并利用高通量技术探索冈比亚按蚊S型异染色质和Y染色体的遗传内容。自动原位杂交、新一代测序、激光显微切割和共焦显微分析设备的可用性，以及 PI 和 Co-PI 在细胞遗传学和基因组学方面的专业知识，将确保该项目目标的成功实现。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 BAC/fosmid 克隆的靶向测序来闭合 S 型组装中的支架间间隙。 2. 将测序支架物理映射并定向到多线染色体。 3. 对 An 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S型。新的基因组组装将使研究人员能够对最完整的测序集进行功能注释，并与其他载体和模型生物体进行更全面的比较基因组学研究。 Y 染色体基因的可用性将使研究人员能够开发性别特异性媒介控制干预措施并对按蚊进行系统发育分析。冈比亚复合体，无基因渗入并发症。科学界将能够从 VectorBase 访问新的组件，以进一步挖掘 An 的特征并进行功能表征。冈比亚基因组。公共卫生相关性：针对负责载体能力的基因是控制传染病的一种新方法。主要非洲疟疾媒介冈比亚按蚊的完整基因组注释将有助于识别流行病学上重要的目标。为了实现这一目标，拟议的项目将利用高通量技术为冈比亚按蚊开发高质量的基因组组装。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Increased production of piRNAs from euchromatic clusters and genes in Anopheles gambiae compared with Drosophila melanogaster.

DOI：
10.1186/s13072-015-0041-5
发表时间：
2015
期刊：
Epigenetics & chromatin
影响因子：
3.9
作者：
George P;Jensen S;Pogorelcnik R;Lee J;Xing Y;Brasset E;Vaury C;Sharakhov IV
通讯作者：
Sharakhov IV

Chromosomal localization of actin genes in the malaria mosquito Anopheles darlingi.

DOI：
10.1111/j.1365-2915.2012.01019.x
发表时间：
2013-03
期刊：
Medical and veterinary entomology
影响因子：
1.9
作者：
Bridi LC;Sharakhova MV;Sharakhov IV;Cordeiro J;Azevedo Junior GM;Tadei WP;Rafael MS
通讯作者：
Rafael MS

A standard cytogenetic map for Anopheles sinensis and chromosome arm homology between the subgenera Anopheles and Cellia.

中华按蚊标准细胞遗传学图谱及按蚊亚属和细胞亚属染色体臂同源性