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dc.contributor.authorDoyle, Stephen R.
dc.contributor.authorIllingworth, Christopher J. R.
dc.contributor.authorLaing, Roz
dc.contributor.authorBartley, David J.
dc.contributor.authorRedman, Elizabeth
dc.contributor.authorMartinelli, Axel
dc.contributor.authorHolroyd, Nancy
dc.contributor.authorMorrison, Alison A.
dc.contributor.authorRezansoff, Andrew
dc.contributor.authorTracey, Alan
dc.contributor.authorDevaney, Eileen
dc.contributor.authorBerriman, Matthew
dc.contributor.authorSargison, Neil
dc.contributor.authorCotton, James A.
dc.contributor.authorGilleard, John S.
dc.date.accessioned2020-07-29T13:22:00Z
dc.date.available2020-07-29T13:22:00Z
dc.date.issued2019
dc.identifier.citationDoyle, S., Illingworth, C., Roz Laing, Bartley, D., Redman, E., Martinelli, A., Holroyd, N., Morrison, A., Rezansoff, A., Tracey, A., Devaney, E., Berriman, M., Sargison, N., Cotton, J., & Gilleard, J. (2019). Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus. Figshare. https://doi.org/10.6084/M9.FIGSHARE.C.4436576.V1
dc.identifier.doi10.6084/m9.figshare.c.4436576.v1
dc.identifier.urihttp://hdl.handle.net/10754/664503
dc.description.abstractAbstract Background Infections with helminths cause an enormous disease burden in billions of animals and plants worldwide. Large scale use of anthelmintics has driven the evolution of resistance in a number of species that infect livestock and companion animals, and there are growing concerns regarding the reduced efficacy in some human-infective helminths. Understanding the mechanisms by which resistance evolves is the focus of increasing interest; robust genetic analysis of helminths is challenging, and although many candidate genes have been proposed, the genetic basis of resistance remains poorly resolved. Results Here, we present a genome-wide analysis of two genetic crosses between ivermectin resistant and sensitive isolates of the parasitic nematode Haemonchus contortus, an economically important gastrointestinal parasite of small ruminants and a model for anthelmintic research. Whole genome sequencing of parental populations, and key stages throughout the crosses, identified extensive genomic diversity that differentiates populations, but after backcrossing and selection, a single genomic quantitative trait locus (QTL) localised on chromosome V was revealed to be associated with ivermectin resistance. This QTL was common between the two geographically and genetically divergent resistant populations and did not include any leading candidate genes, suggestive of a previously uncharacterised mechanism and/or driver of resistance. Despite limited resolution due to low recombination in this region, population genetic analyses and novel evolutionary models supported strong selection at this QTL, driven by at least partial dominance of the resistant allele, and that large resistance-associated haplotype blocks were enriched in response to selection. Conclusions We have described the genetic architecture and mode of ivermectin selection, revealing a major genomic locus associated with ivermectin resistance, the most conclusive evidence to date in any parasitic nematode. This study highlights a novel genome-wide approach to the analysis of a genetic cross in non-model organisms with extreme genetic diversity, and the importance of a high-quality reference genome in interpreting the signals of selection so identified.
dc.publisherfigshare
dc.subjectMedicine
dc.subjectMicrobiology
dc.subjectGenetics
dc.subjectEvolutionary Biology
dc.subject59999 Environmental Sciences not elsewhere classified
dc.subjectEcology
dc.subject69999 Biological Sciences not elsewhere classified
dc.subjectCancer
dc.subject110309 Infectious Diseases
dc.subjectPlant Biology
dc.subject60506 Virology
dc.subjectComputational Biology
dc.titlePopulation genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus
dc.typeDataset
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
dc.contributor.institutionWellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.
dc.contributor.institutionDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
dc.contributor.institutionDepartment of Applied Maths and Theoretical Physics, Wilberforce Road, Cambridge CB3 0WA, UK.
dc.contributor.institutionInstitute of Biodiversity Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Glasgow, G61 1QH, UK.
dc.contributor.institutionMoredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
dc.contributor.institutionDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
dc.contributor.institutionGlobal Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
dc.contributor.institutionUniversity of Edinburgh, Royal (Dick) School of Veterinary Studies, Edinburgh EH25 9RG, UK.
kaust.personMartinelli, Axel
dc.relation.issupplementtoDOI:10.1186/s12864-019-5592-6
display.relations<b> Is Supplement To:</b><br/> <ul> <li><i>[Article]</i> <br/> Doyle SR, Illingworth CJR, Laing R, Bartley DJ, Redman E, et al. (2019) Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus. BMC Genomics 20. Available: http://dx.doi.org/10.1186/s12864-019-5592-6.. DOI: <a href="https://doi.org/10.1186/s12864-019-5592-6" >10.1186/s12864-019-5592-6</a> HANDLE: <a href="http://hdl.handle.net/10754/631748">10754/631748</a></li></ul>


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