New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali.
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/ .
Dara, A; Drábek, EF; Travassos, MA; Moser, KA; Delcher, AL; Su, Q; Hostelley, T; Coulibaly, D; Daou, M; Dembele, A; Diarra, I; Kone, AK; Kouriba, B; Laurens, MB; Niangaly, A; Traore, K; Tolo, Y; Fraser, CM; Thera, MA; Djimde, AA; Doumbo, OK; Plowe, CV; Silva, JC
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