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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI046593-02
Application #
6362434
Study Section
Special Emphasis Panel (ZRG1-BIOL-1 (01))
Program Officer
Gottlieb, Michael
Project Start
2000-03-15
Project End
2003-02-28
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
2
Fiscal Year
2001
Total Cost
$389,052
Indirect Cost
Name
Washington University
Department
Genetics
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Martin, John; Abubucker, Sahar; Wylie, Todd et al. (2009) Nematode.net update 2008: improvements enabling more efficient data mining and comparative nematode genomics. Nucleic Acids Res 37:D571-8
Mitreva, Makedonka; Mardis, Elaine R (2009) Large-scale sequencing and analytical processing of ESTs. Methods Mol Biol 533:153-87
Abubucker, Sahar; Zarlenga, Dante S; Martin, John et al. (2009) The transcriptomes of the cattle parasitic nematode Ostertagia ostartagi. Vet Parasitol 162:89-99
Mitreva, Makedonka; Smant, Geert; Helder, Johannes (2009) Role of horizontal gene transfer in the evolution of plant parasitism among nematodes. Methods Mol Biol 532:517-35
Wang, Zhengyuan; Martin, John; Abubucker, Sahar et al. (2009) Systematic analysis of insertions and deletions specific to nematode proteins and their proposed functional and evolutionary relevance. BMC Evol Biol 9:23
Elling, Axel A; Mitreva, Makedonka; Gai, Xiaowu et al. (2009) Sequence mining and transcript profiling to explore cyst nematode parasitism. BMC Genomics 10:58
Haegeman, Annelies; Jacob, Joachim; Vanholme, Bartel et al. (2009) Expressed sequence tags of the peanut pod nematode Ditylenchus africanus: the first transcriptome analysis of an Anguinid nematode. Mol Biochem Parasitol 167:32-40
Roze, Erwin; Hanse, Bram; Mitreva, Makedonka et al. (2008) Mining the secretome of the root-knot nematode Meloidogyne chitwoodi for candidate parasitism genes. Mol Plant Pathol 9:1-10
Abubucker, Sahar; Martin, John; Yin, Yong et al. (2008) The canine hookworm genome: analysis and classification of Ancylostoma caninum survey sequences. Mol Biochem Parasitol 157:187-92
Wylie, Todd; Martin, John; Abubucker, Sahar et al. (2008) NemaPath: online exploration of KEGG-based metabolic pathways for nematodes. BMC Genomics 9:525

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