African Trypanosome Genome Sequencing

描述(申请人摘要)：非洲锥虫是一种原生动物 在人类中引起一种称为昏睡病的致命疾病的寄生虫 家畜中的ngana。它也是一种非常有价值的实验有机体， 他的研究为生物学的基础发现做出了贡献。按顺序排列 布氏锥虫参考株TREU927/4 GUTat10.1 始于1998年，在基因组研究所(NIAID U01 AI43062)和桑格中心(惠康信托)。自那以后，TIGR提供了一个 以约11,000人的形式绘制染色体图谱的宝贵支架 BAC和P1末端序列，以及大约37,000个基因的猎枪序列 发现号。1999年，我们启动了第二、第四和第六号染色体的测序工作， 使用“即用即用地图”的方法，并将很快产生第一个完整的 非洲锥虫巨型染色体序列(CHR II)。《圣人》 中心已经进行了全染色体的百万数据库染色体测序 绘制的基因组克隆的鸟枪法和快速测序法。他们预计将完成 CHR I序列很快就会完成，并已获得资金对这三个序列进行排序 布鲁氏毛虫最大的染色体(IX、X和XI)。剩下的染色体 (三、五、七和八)由过渡政府间工作组暂时通过。 我们现在建议(I)确定剩余四个序列中的7Mb序列 染色体使用相同的方法成功地对CHR II进行测序，通过 将现有基因组资源与现用图策略相结合，该策略基于 使用来自BAC克隆的末端序列来选择用于测序的最佳克隆； (Ii)对该序列进行分析和注释；及(Iii)制作该序列并 分析可供研究界使用的数据。完整的基因组序列 将在许多层面上提供宝贵的信息和益处， 包括：(1)确定与细胞的基本功能有关的基因 真核细胞，(2)编码基因的简便、廉价和快速克隆 世界各地实验室正在积极研究的蛋白质，(3)即时 获得用于功能/结构研究的基因及其产物，(4) 基于候选基因的代谢途径预测，以及(5) 寄生虫特异性基因产物的鉴定及其与其他基因的比较 基因组。

DESCRIPTION (Applicant's Abstract): The African trypanosome is a protozoan parasite that causes a fatal disease called sleeping sickness in humans and ngana in domestic livestock. It is also a highly valued experimental organism, whose study has contributed fundamental discoveries in biology. Sequencing of the nuclear genome of Trypanosoma brucei reference strain TREU927/4 GUTat10. 1 commenced in 1998 at both The Institute for Genomic Research (NIAID U01 AI43062) and Sanger Centre (Wellcome Trust). TIGR has since provided an invaluable scaffold for chromosome mapping in the form of approximately 11,000 BAC and P1 end sequences, and approximately 37,000 shotgun sequences for gene discovery. In 1999, we initiated the sequencing of chromosomes II, IV and VI, using a 'map-as-you-go' approach; and will shortly produce the first complete sequence of an African trypanosome megabase chromosome (chr II). The Sanger Centre has carried out megabase chromosome sequencing by whole chromosome shotgun and skim sequencing of mapped genomic clones. They expect to complete the sequence of chr I very soon and have secured funding to sequence the three largest chromosomes of T. brucei (IX, X and XI). The remaining chromosomes (III, V, VII and VIII) were provisionally adopted by TIGR. We now propose to (i) determine the 7 Mb sequence of the four remaining chromosomes using the same approach used successfully to sequence chr II, by combining existing genome resources with a map-as-you-go strategy based on the use of end sequences from BAC clones to select optimal clones for sequencing; (ii) analyze and annotate the sequence; and (iii) make the sequence and analysis data available to the research community. The complete genome sequence of T. brucei will provide invaluable information and benefits at many levels, including (1) identification of genes involved in basic functions of the eukaryotic cell, (2) easy, inexpensive and fast cloning of genes encoding proteins being actively studied in laboratories around the world, (3) immediate access to genes and their products for functional/structural studies, (4) prediction of metabolic pathways on the basis of candidate genes, and (5) identification of parasite-specific gene products by comparison with other genomes.