Sequencing of the Leishmania major Friedlin genome is well underway with chromosome 1 (Chr1) and Chr3 having been completely sequenced, and Chr4 virtually complete. Sequencing of several other chromosomes is in progress and the complete genome sequence may be available as soon as 2003. A large proportion (≈ 70%) of the newly identified genes remains unclassified, with many of these being potentially Leishmania (or kinetoplastid-) specific. Most interestingly, the genes are organized into large (> 100–300 kb) polycistronic clusters of adjacent genes on the same DNA strand. Chrl contains two such clusters organized in a ‘divergent’ manner, i.e. the mRNAs for the two sets of genes are both transcribed towards the telomeres. Chr3 contains two ‘convergent’ clusters, with a single ‘divergent’ gene at one telomere, with the two large clusters separated by a tRNA gene. We have characterized several genes from the LD1 (Leishmania DNA 1) region of Chr35. BT1 (formerly ORFG) encodes a biopterin transporter and ORFF encodes a nuclear protein of unknown function. Immunization of mice with recombinant antigens from these genes results in significant reduction in parasite burden following Leishmania challenge. Recombinant ORFF antigen shows promise as a serodiagnostic. We have also developed a tetracycline-regulated promoter system, which allows us to modulate gene expression in Leishmania.
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October 2000
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Conference Article|
October 01 2000
Genomic organization and gene function in Leishmania
P. J. Myler;
*Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109–1651, USA
To whom correspondence should be addressed (e-mail mylerpj@sbri.org)
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E. Sisk;
E. Sisk
*Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109–1651, USA
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P. D. McDonagh;
P. D. McDonagh
*Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109–1651, USA
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S. Martinez-Calvillo;
S. Martinez-Calvillo
*Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109–1651, USA
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A. Schnaufer;
A. Schnaufer
*Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109–1651, USA
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S. M. Sunkin;
S. M. Sunkin
*Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109–1651, USA
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S. Yan;
S. Yan
*Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109–1651, USA
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R. Madhubala;
R. Madhubala
†School of Life Sciences, Jawaharla Nehru University, New Delhi, I 10067, India
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A. Ivens;
A. Ivens
‡Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, U.K.
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K. Stuart
K. Stuart
*Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109–1651, USA
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Publisher: Portland Press Ltd
Received:
June 30 2000
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2000 Biochemical Society
2000
Biochem Soc Trans (2000) 28 (5): 527–531.
Article history
Received:
June 30 2000
Citation
P. J. Myler, E. Sisk, P. D. McDonagh, S. Martinez-Calvillo, A. Schnaufer, S. M. Sunkin, S. Yan, R. Madhubala, A. Ivens, K. Stuart; Genomic organization and gene function in Leishmania. Biochem Soc Trans 1 October 2000; 28 (5): 527–531. doi: https://doi.org/10.1042/bst0280527
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