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Analysis of Plasmodium falciparum var genes expressed in children from Papua New Guinea

Falk, N. and Kaestli, M. and Qi, W. and Ott, M. and Baea, K. and Cortés, A. and Beck, H. P.. (2009) Analysis of Plasmodium falciparum var genes expressed in children from Papua New Guinea. Journal of infectious diseases, Vol. 200, no. 3. pp. 347-356.

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Official URL: http://edoc.unibas.ch/dok/A5843137

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Abstract

Background: The variable antigen P. falciparum erythrocyte membrane protein-1 (PfEMP1) is a major virulence factor in malaria. A large number of var genes encode PfEMP1, and we hypothesized that a restricted PfEMP1 repertoire determines clinical disease presentation. We conducted a case-control study in Papua New Guinea and analyzed transcribed var genes in naturally infected children. Methods: var messenger RNA was isolated from 78 children with asymptomatic, mild, or severe malaria. We prepared complementary DNA from the upstream region into the DBL1alpha domain and picked, on average, 20 clones for sequencing. RESULTS: Twenty-five percent of centrally located var genes were shared between children, whereas only 5% of subtelomeric genes were shared, indicating lower diversity in the former group. Linkage between group B or C var upstream sequences and DBL1alpha groups was not observed, which impeded prediction by DBL1alpha analysis. A higher proportion of var group A sequences was detected in symptomatic malaria, and a subgroup of frequently encountered var genes with complex head structure seems to be associated with severe malaria. A subset of var group C genes was frequently expressed in older children with asymptomatic high levels of parasitemia. CONCLUSION: Despite this vast diversity, restricted disease-associated var genes were identified and might be used for innovative interventions based on PfEMP1
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Molecular Parasitology and Epidemiology (Beck)
UniBasel Contributors:Beck, Hans-Peter
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0022-1899
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Nov 2014 08:28
Deposited On:14 Sep 2012 06:39

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