The African trypanosome is a protozoan parasite that causes a fatal disease called sleeping sickness in humans and ngana in domestic livestock. It is also a highly valued experimental organism, whose study has contributed fundamental discoveries in biology. Sequencing of the nuclear genome of Trypanosoma brucei reference strain TREU927/4 GUTat10. 1 commenced in 1998 at both The Institute for Genomic Research (NIAID U01 AI43062) and Sanger Centre (Wellcome Trust). TIGR has since provided an invaluable scaffold for chromosome mapping in the form of approximately 11,000 BAC and P1 end sequences, and approximately 37,000 shotgun sequences for gene discovery. In 1999, we initiated the sequencing of chromosomes II, IV and VI, using a 'map-as-you-go' approach; and will shortly produce the first complete sequence of an African trypanosome megabase chromosome (chr II). The Sanger Centre has carried out megabase chromosome sequencing by whole chromosome shotgun and skim sequencing of mapped genomic clones. They expect to complete the sequence of chr I very soon and have secured funding to sequence the three largest chromosomes of T. brucei (IX, X and XI). The remaining chromosomes (III, V, VII and VIII) were provisionally adopted by TIGR. We now propose to (i) determine the 7 Mb sequence of the four remaining chromosomes using the same approach used successfully to sequence chr II, by combining existing genome resources with a map-as-you-go strategy based on the use of end sequences from BAC clones to select optimal clones for sequencing; (ii) analyze and annotate the sequence; and (iii) make the sequence and analysis data available to the research community. The complete genome sequence of T. brucei will provide invaluable information and benefits at many levels, including (1) identification of genes involved in basic functions of the eukaryotic cell, (2) easy, inexpensive and fast cloning of genes encoding proteins being actively studied in laboratories around the world, (3) immediate access to genes and their products for functional/structural studies, (4) prediction of metabolic pathways on the basis of candidate genes, and (5) identification of parasite-specific gene products by comparison with other genomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01AI043062-04
Application #
6326608
Study Section
Special Emphasis Panel (ZRG1-GNM (02))
Program Officer
Gottlieb, Michael
Project Start
1998-04-01
Project End
2004-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
4
Fiscal Year
2001
Total Cost
$699,330
Indirect Cost
Name
Institute for Genomic Research
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20850
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Djikeng, Appolinaire; Raverdy, Sylvine; Foster, Jeremy et al. (2007) Cofactor-independent phosphoglycerate mutase is an essential gene in procyclic form Trypanosoma brucei. Parasitol Res 100:887-92
Bringaud, Frederic; Ghedin, Elodie; Blandin, Gaelle et al. (2006) Evolution of non-LTR retrotransposons in the trypanosomatid genomes: Leishmania major has lost the active elements. Mol Biochem Parasitol 145:158-70
Bringaud, Frederic; Bartholomeu, Daniella C; Blandin, Gaelle et al. (2006) The Trypanosoma cruzi L1Tc and NARTc non-LTR retrotransposons show relative site specificity for insertion. Mol Biol Evol 23:411-20
Berriman, Matthew; Ghedin, Elodie; Hertz-Fowler, Christiane et al. (2005) The genome of the African trypanosome Trypanosoma brucei. Science 309:416-22
Horn, David; Barry, J David (2005) The central roles of telomeres and subtelomeres in antigenic variation in African trypanosomes. Chromosome Res 13:525-33
Ersfeld, Klaus; Barraclough, Helen; Gull, Keith (2005) Evolutionary relationships and protein domain architecture in an expanded calpain superfamily in kinetoplastid parasites. J Mol Evol 61:742-57
Ghedin, Elodie; Bringaud, Frederic; Peterson, Jeremy et al. (2004) Gene synteny and evolution of genome architecture in trypanosomatids. Mol Biochem Parasitol 134:183-91
El-Sayed, Najib M A; Ghedin, Elodie; Song, Jinming et al. (2003) The sequence and analysis of Trypanosoma brucei chromosome II. Nucleic Acids Res 31:4856-63
LaCount, D J; El-Sayed, N M; Kaul, S et al. (2001) Analysis of a donor gene region for a variant surface glycoprotein and its expression site in African trypanosomes. Nucleic Acids Res 29:2012-9

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