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。继疟疾之后，血吸虫病是 最流行的热带疾病和严重发病率的主要原因， 发展中国家。该病在74个发展中国家流行， 估计有6亿人处于危险之中，超过2亿人受到感染。的 染色体组约270 Mb，分为8对染色体。 在世界卫生组织的主持下， 90年代，鼓励和协调对染色体的基因组研究。其 总体目标是获得有关这些寄生虫基因组的知识， 进一步了解它们的生物学、耐药性机制， 抗原变异决定了它能逃脱宿主的免疫系统。之一 该计划的主要目标是发现和表征 S.为了寻找新的药物靶点， 和疫苗开发。作为实现这一目标的第一步，博士。 Cummings和她在TIGR的同事将对7 Mb的不连续DNA进行测序， 序列使用BAC末端测序方法获得随机分布的STS 在基因组中每隔20 kb荧光原位杂交 有丝分裂中期染色体的荧光原位杂交（FISH）将用于绘制染色体图谱。 数百个标记的位置PI还将监督测序， 来自染色体3的连续DNA序列上的5Mb注释，ch3。最小 靠近ch3的着丝粒和长臂的区域的BAC平铺路径是 目前正在建设中。为此，末端序列和 将为每个BAC克隆定义限制性模式，一系列10% 将选择重叠的BAC并用于制备BAC霰弹枪小插入物 将其亚文库测序至8倍覆盖。DNA序列来自 将对该区域进行组装，并对以下差距闭合进行全面注释 从而鉴定出了数百个新的染色体基因， 这将为我们对染色体和基因组的研究带来新的见解 organization.

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.