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Title: Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
Authors: John A. Lees
Nicholas J. Croucher
David Goldblatt
François Nosten
Julian Parkhill
Claudia Turner
Paul Turner
Stephen D. Bentley
Wellcome Trust Sanger Institute
Imperial College London
UCL Institute of Child Health
Mahidol University
Nuffield Department of Clinical Medicine
Angkor Hospital for Children
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 25-Jul-2017
Citation: eLife. Vol.6, (2017)
Abstract: © Lees et al. Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance.
ISSN: 2050084X
Appears in Collections:Scopus 2016-2017

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