COMPLETE GENOME SEQUENCE OF MYCOBACTERIUM TUBERCULOSIS

结核分枝杆菌全基因组序列

• 批准号: 2429513
• 负责人: ROBERT D FLEISCHMANN
• 金额: $ 102.4万
• 依托单位: INSTITUTE FOR GENOMIC RESEARCH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-15 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2429513
• 关键词: DNA; Mycobacterium tuberculosis; bacterial genetics; computer assisted sequence analysis; genetic library; genetic mapping; genome; molecular cloning; nucleic acid sequence; polymerase chain reaction

DESCRIPTION (Adapted from the Investigator's Abstract): The goal of this project is to determine the complete DNA sequence of the chromosome of Mycobacterium tuberculosis, the causative agent in tuberculosis. About one third of the world's population is believed to harbor latent tuberculosis. Despite little knowledge about the biology of M. tuberculosis, tuberculosis was widely thought to be under control from the 1950's through the 1980's through the use of multiple drug therapy and better living conditions. However, since the mid 1980's there has been an alarming increase in the rate of tuberculosis infection in developed as well as in developing nations that is primarily attributable to the expanding HIV epidemic, decaying public health services, and the emergence of multiple-drug resistant tuberculosis. Today, tuberculosis remains the leading cause of death due to infection worldwide. It is clear that the complete genomic DNA sequence and a set of recombinant clones would provide a tremendous resource for the study of M. tuberculosis. With the recent demonstration that the complete genome sequence can be obtained from microbial organisms rapidly and cost effectively, the M. tuberculosis genome project is now feasible. The approach will be a whole genome random sequencing strategy. This will be accomplished by constructing a random small insert plasmid library from M. tuberculosis strain H37Rv and sequencing the ends from approximately 35,000 clones (70,000 sequence fragments). The sequencing of the ends of a set of available minimally overlapping cosmid clones will provide a scaffolding structure that will minimize the effort associated with gap filling and provide confirmation of the underlying assembled structure. The assembled genome will then be annotated by identifying a variety of structural features as well as assigning genes and functional roles to open reading frames based on database similarity searches. This approach will accelerate studies in understanding the biology of M. tuberculosis and will impact for example vaccine development, identification of virulence genes, understanding mechanisms of multiple drug resistance, and rational drug therapy. The data developed from this study will be deposited in McyDB which will allow researchers to access the large amount of information on sequences, functions, clones, and other physical map features that will be generated and linked to other features such as antigen, antibody, gene locus and MedLine references.

描述（改编自研究者的摘要）：本研究的目标 项目是确定染色体的完整DNA序列 结核分枝杆菌，结核病的病原体。 大约一 据信世界上三分之一的人口患有潜伏性结核病。 尽管人们对结核分枝杆菌的生物学知之甚少，但结核病 人们普遍认为从 1950 年代到 1980 年代都受到控制 通过使用多种药物治疗和更好的生活条件。 然而，自 20 世纪 80 年代中期以来， 发达国家和发展中国家的结核病感染率 这主要归因于艾滋病毒流行的扩大、艾滋病毒流行的衰退 公共卫生服务和多重耐药性的出现 结核。 如今，结核病仍然是导致死亡的主要原因 感染全球。 很明显，完整的基因组DNA序列和 一组重组克隆将为人类提供巨大的资源 结核分枝杆菌的研究。 随着最近的演示，完整的 可快速从微生物中获取基因组序列，且成本低 实际上，结核分枝杆菌基因组计划现已可行。 该方法将是全基因组随机测序策略。 这将 通过构建随机小插入质粒库来完成 结核分枝杆菌菌株 H37Rv 并对末端进行测序，大约为 35,000 个克隆（70,000 个序列片段）。 a 末端的排序 一组可用的最小重叠粘粒克隆将提供 脚手架结构将最大限度地减少与间隙相关的工作量 填充并提供底层组装结构的确认。 这 然后，组装的基因组将通过识别各种 结构特征以及分配基因和功能角色以打开 基于数据库相似性搜索的阅读框架。 这种方法将 加速了解结核分枝杆菌生物学的研究并将 影响例如疫苗开发、毒力基因鉴定、 了解多重耐药机制，合理用药 治疗。 本研究开发的数据将存储在 McyDB 中 这将使研究人员能够访问有关的大量信息 序列、功能、克隆和其他物理图谱特征 生成并链接到其他特征，例如抗原、抗体、基因位点 和 MedLine 参考文献。