Imperial College London
Alternate

ProfessorMaria-GloriaBasanez

Faculty of Medicine, School of Public Health

Professor of Neglected Tropical Diseases
 
 
 
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Contact

 

+44 (0)20 7594 3295m.basanez Website

 
 
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Location

 

503School of Public HealthWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Doyle:2017:10.1371/journal.pntd.0005816,
author = {Doyle, SR and Bourguinat, C and Nana-Djeunga, HC and Kengne-Ouafo, JA and Pion, SDS and Bopda, J and Kamgno, J and Wanji, S and Che, H and Kuesel, AC and Walker, M and Basanez, M-G and Boakye, DA and Osei-Atweneboana, MY and Boussinesq, M and Prichard, RK and Grant, WN},
doi = {10.1371/journal.pntd.0005816},
journal = {PLoS Neglected Tropical Diseases},
title = {Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity},
url = {http://dx.doi.org/10.1371/journal.pntd.0005816},
volume = {11},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundTreatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana—exposed to more than a decade of regular ivermectin treatment—have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Methodology/Principal findingsPooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.Conclusions/SignificanceThis study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in differe
AU  - Doyle,SR
AU  - Bourguinat,C
AU  - Nana-Djeunga,HC
AU  - Kengne-Ouafo,JA
AU  - Pion,SDS
AU  - Bopda,J
AU  - Kamgno,J
AU  - Wanji,S
AU  - Che,H
AU  - Kuesel,AC
AU  - Walker,M
AU  - Basanez,M-G
AU  - Boakye,DA
AU  - Osei-Atweneboana,MY
AU  - Boussinesq,M
AU  - Prichard,RK
AU  - Grant,WN
DO  - 10.1371/journal.pntd.0005816
PY  - 2017///
SN  - 1935-2727
TI  - Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity
T2  - PLoS Neglected Tropical Diseases
UR  - http://dx.doi.org/10.1371/journal.pntd.0005816
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000408057300096&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/50581
VL  - 11
ER  -
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