Cited by 165Malaria Research and ControlBlood groups and transfusionBird parasitology and diseases

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Global genetic diversity and evolution of var genes associated with placental and severe childhood malaria

Trimnell, Adama R., Kraemer, Susan M., Mukherjee, Sandeep, Phippard, David J., Janes, Joel H., Flamoe, Eric, Su, Xin-zhuan, Awadalla, Philip, Smith, Joseph D.·2006·Molecular and Biochemical Parasitology

DOI 10.1016/j.molbiopara.2006.03.012

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Abstract

In Plasmodium falciparum, var genes encode adhesive proteins that are transported to the surface of infected erythrocytes and act as major virulence determinants for infected erythrocyte binding and immune evasion. Var genes are highly diverse and can be classified into five major groups (UpsA, B, C, D, and E). Previous serological studies have suggested that the UpsA var group may contain common antigenic types that have important roles in severe childhood malaria. Here, our analysis found that UpsA vars are highly diverse between 22 world-wide parasite isolates, although they could be grouped into two broad clusters that may be separately recombining. By comparison, orthologs of the UpsA-linked Type 3 var and UpsE-linked var2csa were detected in nearly all parasite isolates, and a var2csa ortholog was also present in a chimpanzee malaria P. reichenowi that diverged from P. falciparum approximately 5-7 million years ago. Although the specific function of Type 3 var genes is unknown, var2csa is a leading candidate for a pregnancy associated malaria vaccine. Compared to typical var genes, var2csa is unusually conserved but still had only 54-94% amino acid identity in extracellular binding regions. However, var2csa alleles have extensive gene mosaicism within polymorphic blocks that are shared between world-wide parasite isolates and recognizable in P. rechenowi suggesting a high rate of self-self recombination and an ancient and globally-related pool of var2csa polymorphism. T…

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Authors: Trimnell, A. R., Kraemer, S. M., Mukherjee, S., Phippard, D. J., Janes, J. H., Flamoe, E., Su, X.-Z., Awadalla, P., & Smith, J. D.
Affiliations: Center for Infectious Disease Research (US)
National Institutes of Health (US)
North Carolina State University (US)
Corresponding author: Awadalla, Philip
Smith, Joseph D.
ORCID: Su, Xin-zhuan
Awadalla, Philip
Smith, Joseph D.
Venue: Molecular and Biochemical Parasitology
Publisher: Elsevier BV
Published: 2006-08
Volume: 148
Issue: 2
Pages: 169-180
ISSN: 0166-6851 (ISSN-L)
DOI: 10.1016/j.molbiopara.2006.03.012
OpenAlex: W1996773860
Cited by: 165
References: 57
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 8 · 2016: 1 · 2015: 8 · 2014: 14 · 2013: 11 · 2012: 14
FWCI: 19.64
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Molecular and Biochemical Parasitology (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
European Commission
National Institute of Allergy and Infectious Diseases (R01AI047953, R01 AI4795301A1)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Health Sciences › Medicine › Hematology › Blood groups and transfusion
Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
Keywords: Plasmodium falciparum, var genes, VAR2CSA, placental malaria, Plasmodium reichenowi, erythrocyte adhesion, immune evasion
MeSH terms: Amino Acid Sequence, Animals, Antigenic Variation, Child, Female, Humans, Molecular Sequence Data, Placenta, Placenta Diseases, Plasmodium falciparum, Pregnancy, Severity of Illness Index, Genetic Variation, Pregnancy Complications, Parasitic, Malaria, Falciparum, Genes, Protozoan, Sequence Analysis, DNA, Evolution, Molecular

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Global genetic diversity and evolution of var genes associated with placental and severe childhood malaria

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