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Doyle S. R., Bourguinat C., Nana-Djeunga H. C., Kengne-Ouafo J. A., Pion Sébastien, Bopda J., Kamgno J., Wanji S., Che H., Kuesel A. C., Walker M., Basanez M. G., Boakye D. A., Osei-Atweneboana M. Y., Boussinesq Michel, Prichard R. K., Grant W. N. (2017). Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity. PLOS Neglected Tropical Diseases, 11 (7), e0005816 [31 p.]. ISSN 1935-2735

Fichier PDF disponible http://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers17-09/010070934.pdf

Lien direct chez l'éditeur doi:10.1371/journal.pntd.0005816

Titre
Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity
Année de publication2017
Type de documentArticle référencé dans le Web of Science WOS:000408057300096
AuteursDoyle S. R., Bourguinat C., Nana-Djeunga H. C., Kengne-Ouafo J. A., Pion Sébastien, Bopda J., Kamgno J., Wanji S., Che H., Kuesel A. C., Walker M., Basanez M. G., Boakye D. A., Osei-Atweneboana M. Y., Boussinesq Michel, Prichard R. K., Grant W. N.
SourcePLOS Neglected Tropical Diseases, 2017, 11 (7), p. e0005816 [31 p.]. p. e0005816 [31 p.] ISSN 1935-2735
RésuméBackground 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 similar to 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.
Plan de classementEntomologie médicale / Parasitologie / Virologie [052] ; Santé : généralités [050]
Descr. géo.GHANA ; CAMEROUN ; AFRIQUE SUBSAHARIENNE
LocalisationFonds IRD [F B010070934]
Identifiant IRDfdi:010070934
Lien permanenthttp://www.documentation.ird.fr/hor/fdi:010070934

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