Parasitic nematodes infect over half the world's human population, resulting in significant morbidity. Nematodes also attack livestock and cause over 80 billion dollars in crop damage annually. The essentially complete genome sequence of C. elegans offers a wealth of information about nematodes that could lead to new drugs, pesticides and vaccines. To expedite identification of genes from parasites which correspond to C. elegans, we propose a large-scale Expressed Sequence Tag (EST) sequencing effort that will target medically and economically important parasites from across the phylum Nematoda. ESTs have been demonstrated to provide a rapid partial inventory of an organism's genes for a fraction of the cost of a complete genome project. The objective of this project is to generate and analyze a total of 125,000 ESTs from five key parasites: human hookworm (Necator americanus), two human intestinal works (Ascaris lumbricoides and Strongyloides stercoralis), a mouse intestinal worm (Trichuris muris), and soybean cyst nematode (Heterodera glycines). Specifically, the project will consist of generating directionally cloned cDNA libraries, obtaining ESTs from cDNA clones, and immediately submitting this data to the public databases. Homologues of C. elegans genes will be identified by BLAST, FASTA, and HMM techniques. Attention will be given to identifying proteins which have high similarity to C. elegans homologues but only weak similarity to non-nematode genomes. Such phyla-specific proteins are of interest, since they may serve as biochemical targets for the development of highly specific, non-toxic drugs and environmentally safe pesticides.
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