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 Bopda, J.
dc.contributor.author Kamgno, J.
dc.contributor.author Wanji, S.
dc.contributor.author Kuesel, A. C.
dc.contributor.author Walker, M.
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 2019-08-08T12:37:58Z
dc.date.available 2019-08-08T12:37:58Z
dc.date.issued 2017
dc.identifier.other vol.11(7): e0005816
dc.identifier.other DOI:10.1371/journal.pntd.0005816
dc.identifier.uri http://ugspace.ug.edu.gh/handle/123456789/31946
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 PLoS Neglected Tropical Diseases 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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  • Bacteriology Department [105]
    The Bacteriology Department aims to improve the quality of life first for Ghanaians and the world at large by conducting research into bacterial diseases of public health importance to Ghana and globally. In addition to working on enteric pathogens and sexually transmitted diseases, the department’s current main focus is on the two most important mycobacterial diseases of public health importance to Ghana, namely Buruli ulcer (BU) and tuberculosis (TB).

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