ArticleMalaria journal2012
Genetic diversity of expressed Plasmodium falciparum var genes from Tanzanian children with severe malaria.
Article in Malaria journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Plasmodium falciparum expresses fewer var genes at lower levels during asymptomatic dry season infections than clinical malaria cases.PLoS pathogens · 2025Article
- GenotypingIndian journal of microbiology · 2024Article
- Analysis of var Gene Transcription Pattern Using DBLα Tags.Methods in molecular biology (Clifton, N.J.) · 2022Article
- VAPPER: High-throughput variant antigen profiling in African trypanosomes of livestock.GigaScience · 2019Article
- Variant antigen repertoires inGenome research · 2018Article
- In silico guided reconstruction and analysis of ICAM-1-binding var genes from Plasmodium falciparum.Scientific reports · 2018Article
- Evolutionary structure ofEcology and evolution · 2017Article
- Differential PfEMP1 expression is associated with cerebral malaria pathology.PLoS pathogens · 2014Article
- CD4+ T cell responses to the Plasmodium falciparum erythrocyte membrane protein 1 in children with mild malaria.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
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Abstract
backgroundSevere malaria has been attributed to the expression of a restricted subset of the var multi-gene family, which encodes for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 mediates cytoadherence and sequestration of infected erythrocytes into the post-capillary venules of vital organs such as the brain, lung or placenta. var genes are highly diverse and can be classified in three major groups (ups A, B and C) and two intermediate groups (B/A and B/C) based on the genomic location, gene orientation and upstream sequences. The genetic diversity of expressed var genes in relation to severity of disease in Tanzanian children was analysed.
methodsChildren with defined severe (SM) and asymptomatic malaria (AM) were recruited. Full-length var mRNA was isolated and reversed transcribed into var cDNA. Subsequently, the DBL and N-terminal domains, and up-stream sequences were PCR amplified, cloned and sequenced. Sequences derived from SM and AM isolates were compared and analysed.
resultsThe analysis confirmed that the var family is highly diverse in natural Plasmodium falciparum populations. Sequence diversity of amplified var DBL-1α and upstream regions showed minimal overlap among isolates, implying that the var gene repertoire is vast and most probably indefinite in endemic areas. var DBL-1α sequences from AM isolates were more diverse with more singletons found (p<0.05) than those from SM infections. Furthermore, few var DBL-1α sequences from SM patients were rare and restricted suggesting that certain PfEMP1 variants might induce severe disease.
conclusionsThe genetic sequence diversity of var genes of P. falciparum isolates from Tanzanian children is large and its relationship to disease severity has been studied. Observed differences suggest that different var genes might have fundamentally different roles in the host-parasite interaction. Further research is required to examine clear disease-associations of var gene subsets in different geographical settings. The importance of very strict clinical definitions and appropriate large control groups needs to be emphasized for future studies on disease associations of PfEMP1.
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