SEQUENCING 12 MB OF THE SCHISTOSOMA MANSONI GENOME

描述(研究者摘要)：曼氏血吸虫是一种吸虫 引起血吸虫病的寄生虫。在疟疾之后，血吸虫病是 年最流行的热带病和严重发病的主要原因 发展中国家。这种疾病在74个发展中国家流行， 估计有6亿人处于危险之中，超过2亿人感染。这个 血吸虫基因组全长约270Mb，由8对染色体组成。 在世界卫生组织的主持下，在#年成立了一个国际财团 90年代，S鼓励和协调血吸虫基因组研究。它的 总体目标是按顺序获得关于这些寄生虫基因组的知识 为了进一步了解它们的生物学、耐药机制和 决定逃避宿主免疫系统的抗原变异。其中之一 该计划的主要目标是发现和表征 曼氏血吸虫新基因及寻找药物新靶点的尝试 和疫苗的开发。作为实现这一目标的初步步骤。 卡明斯和她在TIGR的同事将对7Mb的不连续DNA进行测序 使用BAC末端排序方法获得随机分布的STS的序列 以大约每20kb的速度横跨基因组。荧光原位杂交 (FISH)到有丝分裂中期的染色体将被用来定位染色体 数百个这样的标记的位置。私家侦探还将监督排序和 3号染色体CH3相邻DNA序列上5Mb的注释最低要求 CH3着丝粒和长臂附近区域的BAC平铺路径为 目前正在建设中。为此，终端序列和 将为每个BAC克隆定义限制模式，系列为10% 将选择重叠的BAC并将其用于制备BAC猎枪小插件 子库将被排序为8倍的覆盖率。来自中国的DNA序列 将对该区域进行组装，并将对缝隙闭合进行完整注记 可能导致了数百个新的血吸虫基因的鉴定 这将为血吸虫染色体和基因组提供新的见解 组织。

DESCRIPTION (Investigator's Abstract): Schistosoma mansoni is a trematode parasite that causes schistosomiasis. After malaria, schistosomiasis is the most prevalent tropical disease and leading cause of severe morbidity in developing nations. The disease is endemic in 74 developing countries, with estimates of 600 million people at risk and over 200 million infected. The schistosome genome is approximately 270 Mb, organized into 8 chromosome pairs. Under the auspices of the WHO, an international consortium was established in the 90's to encourage and coordinate genomic research on schistosomes. Its overall aim is to gain knowledge about the genome of these parasites in order to further understanding of their biology, mechanisms of drug resistance and antigenic variation that determine escape from the host's immune system. One of the main objectives of this program is the discovery and characterization of new genes of S. mansoni and in an attempt to search for new targets for drugs and vaccine development. As a preliminary step to achieving this goal, Dr. Cummings and her colleagues at TIGR will sequence 7 Mb of discontinuous DNA sequence using a BAC-end sequencing approach to obtain STS randomly distributed across the genome at about every 20 kb. Flourescent in situ hybridization (FISH) to mitotic metaphase chromosomes will be used to map the chromosomal locations of hundreds of these markers. The PI will also oversee sequencing and annotation of 5 Mb on contiguous DNA sequence from chromosome 3, ch3. A minimum BAC tiling path for a region near the centromere and long arm of ch3 is currently being constructed. For this purpose, terminal sequences and restriction patterns will be defined for each BAC clone, A series of 10 percent overlapping BACs will be selected and used to prepare BAC shotgun small insert sublibraries which will be sequenced to 8 fold coverage. The DNA sequence from this region will be assembled and following gap closure will be full annotated leading to the identification of perhaps hundreds of new schistosome genes which will revel new insights into schistosome chromosome and genome organization.