SEQUENCING 12 MB OF THE SCHISTOSOMA MANSONI GENOME

Institute For Genomic Research, Rockville MD

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Abstract

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.