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Genome Med. 2017 Mar 28;9(1):30. doi: 10.1186/s13073-017-0422-4.

New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali.

Author information

1
Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
2
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
3
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali.
4
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
5
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
6
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. jcsilva@som.umaryland.edu.
7
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA. jcsilva@som.umaryland.edu.

Abstract

BACKGROUND:

Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40-60 var gene complement for individual infections has been notoriously difficult, impeding molecular epidemiological studies and the assessment of particular var elements as subunit vaccine candidates.

METHODS:

We developed and validated a novel algorithm, Exon-Targeted Hybrid Assembly (ETHA), to perform targeted assembly of var gene sequences, based on a combination of Pacific Biosciences and Illumina data.

RESULTS:

Using ETHA, we characterized the repertoire of var genes in 12 samples from uncomplicated malaria infections in children from a single Malian village and showed them to be as genetically diverse as vars from isolates from around the globe. The gene var2csa, a member of the var family associated with placental malaria pathogenesis, was present in each genome, as were vars previously associated with severe malaria.

CONCLUSION:

ETHA, a tool to discover novel var sequences from clinical samples, will aid the understanding of malaria pathogenesis and inform the design of malaria vaccines based on PfEMP1. ETHA is available at: https://sourceforge.net/projects/etha/ .

KEYWORDS:

ETHA; Malaria; Mali; PfEMP1; Plasmodium falciparum; Plasmodium falciparum erythrocyte membrane protein-1; var; var2csa

PMID:
28351419
PMCID:
PMC5368897
DOI:
10.1186/s13073-017-0422-4
[Indexed for MEDLINE]
Free PMC Article

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