期刊
GENOME MEDICINE
卷 9, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s13073-017-0422-4
关键词
Malaria; Plasmodium falciparum; Plasmodium falciparum erythrocyte membrane protein-1; PfEMP1; var; var2csa; Mali; ETHA
资金
- National Institute of Allergy and Infectious Diseases (NIAID) [U19AI065683]
- National Institutes of Health (NIH)
- NIAID/NIH GSCID [HHSN272200900009C]
- NIAID/NIH [U19AI110820]
- NIH [D43TW001589]
- Fogarty International Center
- Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship
- Howard Hughes Medical Institute
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.
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