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TARGET ORGANISMS
Trypanosomatids and Plasmodia
These protozoa afflict approximately 500 million people per year, mostly in the tropics and subtropics. The resulting diseases cause disability, disfigurement, and in some cases death. Vaccines against these single cell organisms seem unlikely due to antigenic variation. Additionally, these protozoa promote drug resistance via multiple pathways. The drugs currently available to destroy these parasites are toxic to humans themselves. Overall, our problem with pathogenic protozoa is understudied; however, these issues are pertinent given the human toll.
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Predicted Number of Parasite Genes
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Organism
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P. falciparum
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L. major
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T. brucei
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T. cruzi
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Genome
size
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25 MB
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34 MB
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25 MB+
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~40 MB
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Sequencing
Centers
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Sanger
TIGR
Stanford
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SBRI
Sanger
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TIGR
Sanger
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SBRI
TIGR
Karolinska
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Approach
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Chromosome
shotgun
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Large clone &
Chromosome
shotgun
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Large clone &
Chromosome
shotgun
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Whole genome
shotgun
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Status
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First draft
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5 chr
finished, rest
in finishing
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2 chr
finished, rest
in shotgun
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In shotgun
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# of genes
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"5342"
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~8500
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~8500
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~8500
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For T. cruzi there may actually be twice as many genes if you count the two homologs of each, since they may differ by several percent.
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Unusual Features of the Targeted Protozoa
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Antigenic variation and variability of surface proteins
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Proteins of protozoa that modify host cells and immune response
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Many surface proteins are attached by GPI anchors
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Rhoptry organelles, unique to apicoplasts, in Plasmodia
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Plastid organelles, related to plant chloroplasts, in Plasmodia
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Flagellar pocket of trypanosomatids, distinct function in secretion and importation
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Parasitophorous vacuoles surrounding intracellular forms
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Glycosomes of trypanosomatids
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Food vacuoles of Plasmodia
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Trans-splicing of mRNA and lack of introns in trypanosomatids
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Extensive RNA editing in mitochondria of trypanosomatids
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Unique transcriptional control of trypanosomatids
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Plasmodium falciparum sporozoites travel through hepatocytes
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