Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patientsReportar como inadecuado




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Reference: Robinson, T, Campino, SG, Auburn, S et al., (2011). Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients. PLoS One, 6 (8), Article: e23204.Citable link to this page:

 

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients

Abstract: Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Foundation for Innovative New Diagnostics   Funder: UCL Hospitals Comprehensive Biomedical Research Centre for Infection   Funder: United Kingdom Health Protection Agency   Funder: Wellcome Trust   Funder: MRC Centre for Genomics and Global Health   Notes:Copyright 2011 Robinson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website: http://www.plos.org

Journal: PLoS Onesee more from them

Publication Website: http://www.plosone.org

Issue Date: 2011

pages:Article: e23204Identifiers

Urn: uuid:444cd13e-d409-417e-886d-0f8a6c0d0a8d

Source identifier: 172054

Eissn: 1932-6203

Doi: https://doi.org/10.1371/journal.pone.0023204

Issn: 1932-6203 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Humans Plasmodium falciparum Malaria Protozoan Proteins Antigens, Protozoan Sequence Analysis, DNA Base Sequence Gene Dosage Haplotypes Genes, Protozoan Sequence Deletion Molecular Sequence Data Adult Genetic Loci Genome, Mitochondrial Genome Middle Aged Chromosomes Clone Cells Polymorphism, Single Nucleotide Drug Resistance High-Throughput Nucleotide Sequencing Tiny URL: pubs:172054

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Autor: Robinson, T - institutionUniversity of Oxford - - - Campino, SG - - - Auburn, S - - - Assefa, SA - - - Polley, SD - - - Manske, M

Fuente: https://ora.ox.ac.uk/objects/uuid:444cd13e-d409-417e-886d-0f8a6c0d0a8d



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