Ontology highlight
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/ .
SUBMITTER: Dara A
PROVIDER: S-EPMC5368897 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Dara Antoine A Drábek Elliott F EF Travassos Mark A MA Moser Kara A KA Delcher Arthur L AL Su Qi Q Hostelley Timothy T Coulibaly Drissa D Daou Modibo M Dembele Ahmadou A Diarra Issa I Kone Abdoulaye K AK Kouriba Bourema B Laurens Matthew B MB Niangaly Amadou A Traore Karim K Tolo Youssouf Y Fraser Claire M CM Thera Mahamadou A MA Djimde Abdoulaye A AA Doumbo Ogobara K OK Plowe Christopher V CV Silva Joana C JC
Genome medicine 20170328 1
<h4>Background</h4>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.<h4>Metho ...[more]