TRYPANOSOMA CRUZI GENOME PROJECT AT TIGR

TiGR 克鲁兹锥虫基因组项目

• 批准号: 6652601
• 负责人: Najib M El-Sayed
• 金额: $ 78.64万
• 依托单位: INSTITUTE FOR GENOMIC RESEARCH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-15 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6652601
• 关键词: Internet; Trypanosoma cruzi; artificial chromosomes; computer assisted sequence analysis; genetic library; genetic mapping; genetic markers; genome; information dissemination; microarray technology; molecular biology information system; nucleic acid sequence

Trypanosoma cruzi is a protozoan parasite that causes a fatal illness called Chagas' disease or American typanosomiasis in humans and many nonhuman mammalian species. The World Health Organization has estimated that 18 million people are infected with T. cruzi and that 50,000 patients die each year of the disease. The basic research on T. cruzi over the past two decades has resulted in many advances in our understanding of these organisms, yet these substantial research efforts have not led to a better way to manage or control this devastating disease. Recently, progress on the human genome project, and the determination of the yeast genomic sequence, have unambiguously demonstrated the value of using genomic sequences as a foundation for designing future research efforts. Our long term goal is to sequence the genome of T. cruzi. This proposal, in conjunction with similar proposed efforts at the Seattle Biomedical Research Institute and Uppsala University, represents a large step towards that goal. We will employ a sequencing strategy consisting of two phases. The purpose of the first phase is to enhance early gene discovery and to provide markers that will be important for construction of a high-resolution sequence-ready map. In this phase we will generate approximately 10 Mb of discontinuous single-pass sequence (23 percent of the 43.5 Mb genome). This will be implemented by end-sequencing 5,000 BAC (Bacterial Artificial Chromosome) clones from an already existing library and another 5,000 BAC clones of randomly-sheared DNA (from a library to be constructed in collaboration with Dr. Pieter deJong). Telomere-proximal sequences will be identified in clones of the sheared genonmic library. During the second phase 12 Mb of contiguous T. cruzi DNA will be sequenced using a chromosome by chromosome approach and a syntenic regions conserved between T. cruzi and a related parasite (Trypanosoma brucei) will be identified and analyzed. This project 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, (4) identification of parasite-specific gene products by comparison with other genomes, and (5) a framework for future experiments aimed at comparative and integrative mapping of various trypanosomatid genomes.

克氏锥虫（Trypanosoma cruzi）是一种原生动物寄生虫，在人类和许多非人类哺乳动物物种中引起致命的疾病，称为恰加斯病或美洲锥虫病。 世界卫生组织估计，有1800万人感染了T。每年有五万名病人死于这种疾病。 对T.在过去的二十年里，cruzi使我们对这些生物体的了解取得了许多进展，但这些实质性的研究努力并没有导致更好的方法来管理或控制这种毁灭性的疾病。 最近，人类基因组计划的进展，以及酵母基因组序列的测定，已经明确地证明了使用基因组序列作为设计未来研究工作的基础的价值。 我们的长期目标是对T.克鲁兹 这一提议，加上拟议在西雅图生物医学研究所和乌普萨拉大学进行的类似努力，是朝着这一目标迈出的一大步。 我们将采用由两个阶段组成的排序策略。 第一阶段的目的是加强早期基因的发现，并提供标记，这将是一个高分辨率的序列准备地图的建设是重要的。 在这个阶段，我们将产生大约10 Mb的不连续单程序列（43.5 Mb基因组的23%）。 这将通过对来自现有文库的5，000个BAC（细菌人工染色体）克隆和另外5，000个随机剪切DNA的BAC克隆（来自与Pieter deJong博士合作构建的文库）进行末端测序来实现。 将在剪切的基因文库的克隆中鉴定端粒近端序列。 在第二阶段，12 Mb的连续T. cruzi DNA将使用染色体接染色体的方法和T.将鉴定和分析克氏锥虫和相关寄生虫（布氏锥虫）。 该项目将在许多层面上提供宝贵的信息和益处，包括（1）鉴定涉及真核细胞基本功能的基因，（2）容易、廉价和快速地克隆世界各地实验室正在积极研究的蛋白质编码基因，（3）立即获得基因及其产物用于功能/结构研究，（4）基于候选基因的代谢途径预测，（4）通过与其他基因组的比较来鉴定寄生虫特异性基因产物，以及（5）旨在对各种锥虫基因组进行比较和整合作图的未来实验的框架。