Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

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dc.contributor.author Doyle, S.R.
dc.contributor.author Bourguinat, C.
dc.contributor.author Nana-Djeunga, H.C.
dc.contributor.author Kengne-Ouafo, J.A.
dc.contributor.author Pion, S.D.S.
dc.contributor.author Bopda, J.
dc.contributor.author Kamgno, J.
dc.contributor.author Wanji, S.
dc.contributor.author Che, H.
dc.contributor.author Kuesel, A.C.
dc.contributor.author Walker, M.
dc.contributor.author Basáñez, M.G.
dc.contributor.author Boakye, D.A.
dc.contributor.author Osei-Atweneboana, M.Y.
dc.contributor.author Boussinesq, M.
dc.contributor.author Prichard, R.K.
dc.contributor.author Grant, W.N.
dc.date.accessioned 2017-10-30T09:47:23Z
dc.date.available 2017-10-30T09:47:23Z
dc.date.issued 2017
dc.identifier.issn 19352727
dc.identifier.other 10.1371/journal.pntd.0005816
dc.identifier.uri http://ugspace.ug.edu.gh/handle/123456789/22300
dc.description.abstract Background: Treatment 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 findings: Pooled 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/Significance: This 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 different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations. © 2017 Doyle et al. en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity en_US
dc.type Article en_US


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    The Epidemiology Department contributes to the mission of the institute through basic and applied epidemiological research on, but not limited to, malaria and other diseases of public health importance. It is also home to the Social Science Unit of the Institute, including the Health Support Centre for HIV/AIDS and other communicable and noncommunicable health problems.

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