@article{fdi:010070934,
  title = {{G}enome-wide analysis of ivermectin response by {O}nchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity},
  author = {{D}oyle, {S}. {R}. and {B}ourguinat, {C}. and {N}ana-{D}jeunga, {H}. {C}. and {K}engne-{O}uafo, {J}. {A}. and {P}ion, {S}{\'e}bastien and {B}opda, {J}. and {K}amgno, {J}. and {W}anji, {S}. and {C}he, {H}. and {K}uesel, {A}. {C}. and {W}alker, {M}. and {B}asanez, {M}. {G}. and {B}oakye, {D}. {A}. and {O}sei-{A}tweneboana, {M}. {Y}. and {B}oussinesq, {M}ichel and {P}richard, {R}. {K}. and {G}rant, {W}. {N}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {T}reatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout {A}frica and {C}entral/{S}outh {A}merica. {M}ass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several {O}nchocerca volvulus populations from {C}ameroon and {G}hana-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. {M}ethodology/{P}rincipal findings {P}ooled next generation sequencing ({P}ool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. {G}enome-wide analyses revealed genetic variation that significantly differentiated good responder ({GR}) and sub-optimal responder ({SOR}) parasites. {T}hese variants were not randomly distributed but clustered in similar to 31 quantitative trait loci ({QTL}s), with little overlap in putative {QTL} position and gene content between the two countries. {P}ublished candidate ivermectin {SOR} genes were largely absent in these regions; {QTL}s differentiating {GR} and {SOR} worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. {F}inally, 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}. {C}onclusions/{S}ignificance {T}his 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. {W}e 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. {F}urthermore, 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.},
  keywords = {{GHANA} ; {CAMEROUN} ; {AFRIQUE} {SUBSAHARIENNE}},
  booktitle = {},
  journal = {{PLOS} {N}eglected {T}ropical {D}iseases},
  volume = {11},
  numero = {7},
  pages = {e0005816 [31 p.]},
  ISSN = {1935-2735},
  year = {2017},
  DOI = {10.1371/journal.pntd.0005816},
  URL = {https://www.documentation.ird.fr/hor/fdi:010070934},
}