Wellcome Open Res
Background: Although thousands of clinical isolates of Plasmodium falciparum are being sequenced and analysed by short read technology, the data do not resolve the highly variable subtelomeric regions of the genomes that contain polymorphic gene families involved in immune evasion and pathogenesis. There is also no current standard definition of the boundaries of these variable subtelomeric regions. Methods: Using long-read sequence data (Pacific Biosciences SMRT technology), we assembled and annotated the genomes of 15 P. falciparum isolates, ten of which are newly cultured clinical isolates. We performed comparative analysis of the entire genome with particular emphasis on the subtelomeric regions and the internal var genes clusters. Results: The nearly complete sequence of these 15 isolates has enabled us to define a highly conserved core genome, to delineate the boundaries of the subtelomeric regions, and to compare these across isolates. We found highly structured variable regions in the genome. Some exported gene families purportedly involved in release of merozoites show copy number variation. As an example of ongoing genome evolution, we found a novel CLAG gene in six isolates. We also found a novel gene that was relatively enriched in the South East Asian isolates compared to those from Africa. Conclusions: These 15 manually curated new reference genome sequences with their nearly complete subtelomeric regions and fully assembled genes are an important new resource for the malaria research community. We report the overall conserved structure and pattern of important gene families and the more clearly defined subtelomeric regions.
Otto, T. D., Bohme, U., Sanders, M., Reid, A., Bruske, E. I., Duffy, C. W., Bull, P. C., Pearson, R. D., Abdi, A., Dimonte, S., Stewart, L. B., Campino, S., Kekre, M., Hamilton, W. L., Claessens, A., Volkman, S. K., Ndiaye, D., Amambua-Ngwa, A., Diakite, M., Fairhurst, R. M., Conway, D. J., Franck, M., Newbold, C. I., Berriman, M.
Pages:52, Volume:3, Edition:6/5/2018, Date,
Notes:Otto, Thomas D|Bohme, Ulrike|Sanders, Mandy|Reid, Adam|Bruske, Ellen I|Duffy, Craig W|Bull, Pete C|Pearson, Richard D|Abdi, Abdirahman|Dimonte, Sandra|Stewart, Lindsay B|Campino, Susana|Kekre, Mihir|Hamilton, William L|Claessens, Antoine|Volkman, Sarah K|Ndiaye, Daouda|Amambua-Ngwa, Alfred|Diakite, Mahamadou|Fairhurst, Rick M|Conway, David J|Franck, Matthias|Newbold, Chris I|Berriman, Matt|eng|Wellcome Trust/United Kingdom|MC_EX_MR/K02440X/1/Medical Research Council/United Kingdom|England|2018/06/05 06:00|Wellcome Open Res. 2018 May 3;3:52. doi: 10.12688/wellcomeopenres.14571.1. eCollection 2018.
ISBN: 2398-502X (Print)|2398-502X (Linking) Permanent ID: PMC5964635 Accession Number: 29862326
Author Address: Wellcome Sanger Institute, Hinxton, UK.|Centre of Immunobiology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.|Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany.|London School of Hygiene and Tropical Medicine, London, UK.|Department of Pathology, University of Cambridge, Cambridge, UK.|Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, UK.|KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.|Harvard T.H. Chan School of Public Health, Boston, MA, USA.|The Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Simmons College, Boston, MA, USA.|Faculty of Medicine and Pharmacy, Universite Cheikh Anta Diop, Dakar, Senegal.|Medical Research Council Unit, Fajara, The Gambia.|Malaria Research and Training Center, University of Bamako, Bamako, Mali.|Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.|Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.