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Molecular epidemiology and diagnosis of Leishmania: what have we learnt from genome structure, dynamics and function?

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dc.contributor.author Dujardin, J. C. en_US
dc.contributor.author Victoir, K. en_US
dc.contributor.author De Doncker, S. en_US
dc.contributor.author Guerbouj, S. en_US
dc.contributor.author Arévalo, J. en_US
dc.contributor.author Le Ray, D. en_US
dc.date.accessioned 2007-12-06T14:33:26Z
dc.date.available 2007-12-06T14:33:26Z
dc.date.issued 2002 en_US
dc.identifier.issn 0035-9203 en_US
dc.identifier.doi http://dx.doi.org/10.1016/S0035-9203(02)90056-8
dc.identifier.other ITG-P1A en_US
dc.identifier.other ITG-P2B en_US
dc.identifier.other ITG-P3B en_US
dc.identifier.other ITG-P4B en_US
dc.identifier.other ITG-PLA en_US
dc.identifier.other PARAS en_US
dc.identifier.other U-PROTO en_US
dc.identifier.other JIF en_US
dc.identifier.other DOI en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.uri http://hdl.handle.net/10390/133 en_US
dc.description.abstract This paper reviews our exploration of the dynamics of the Leishmania genome and its contribution to epidemiology and diagnosis. We used as a model Peruvian populations of L. (Viannia) braziliensis and L. (V.) peruviana, 2 species very close phylogenetically, but phenotypically very different in biotope and pathology. We initially focused on karyotype analysis. Our data showed that chromosomes were subject to a fast rate of evolution, and were sensitive indicators of genetic drift. Therefore, molecular karyotyping appeared an adequate tool for monitoring (i) emergence of close species, (ii) ecogeographical differentiation at the intraspecific level, and (iii) strain 'fingerprinting'. Chromosome size variation was mostly due to the number of tandemly repeated genes (rDNA, mini-exon, gp63, and cysteine proteinase genes), and could involve the deletion of unique genes (L. (V.) braziliensis-specific gp63 families). Considering the importance of these genes in parasitism, their rearrangement might have functional implications: adaptation to different environments and pleomorphic pathogenicity. Our knowledge of genome structure and dynamics was used to develop new polymerase chain reaction (PCR) techniques. Amplification of gp63 genes followed by cleavage with restriction enzymes and study of restriction fragment length polymorphism (gp63 PCR-RFLP) allowed the discrimination of all species tested, even directly in biopsies with 95% sensitivity (compared with PCR amplification of kinetoplast deoxyribonucleic acid). At the intra-specific level, RFLP was also observed and corresponded to mutations in major immunogen domains of gp63. These seem to be under strong selection pressure, and the technique should facilitate addressing how the host's immune pressure may modulate parasite population structure. Altogether, gp63 PCR-RFLP represents a significant operational improvement over the other techniques for molecular epidemiology and diagnosis: it combines sensitivity, discriminatory power and prognostic value. en_US
dc.language English en_US
dc.publisher Elsevier
dc.subject Protozoal diseases en_US
dc.subject Leishmaniasis en_US
dc.subject Protozoology en_US
dc.subject Leishmania braziliensis en_US
dc.subject Leishmania peruviana en_US
dc.subject Genomics en_US
dc.subject Molecular biology en_US
dc.subject Diagnosis en_US
dc.subject Epidemiology en_US
dc.subject Chromosomes en_US
dc.subject Karyotyping en_US
dc.subject Peru en_US
dc.subject America, Latin en_US
dc.title Molecular epidemiology and diagnosis of Leishmania: what have we learnt from genome structure, dynamics and function? en_US
dc.type Article en_US
dc.citation.issue Suppl.1 en_US
dc.citation.jtitle Transactions of the Royal Society of Tropical Medicine and Hygiene en_US
dc.citation.volume 96 en_US
dc.citation.pages S81-S86 en_US
dc.publisher.place Amsterdam
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/12055856
dc.identifier.url http://www.elsevier.com/locate/trstmh
dc.citation.jabbreviation Trans R Soc Trop Med Hyg en_US


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