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Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use

Sheep farmers in the UK rely on strategic anthelmintic use to treat and control gastrointestinal roundworms in their flocks. However, resistance to these drugs is now widespread and threatens the sustainability of sheep production. The mechanisms underlying resistance to the most commonly used class...

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Autores principales: Laing, Roz, Maitland, Kirsty, Lecová, Lenka, Skuce, Philip J., Tait, Andy, Devaney, Eileen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011429/
https://www.ncbi.nlm.nih.gov/pubmed/27179994
http://dx.doi.org/10.1016/j.ijpara.2016.03.010
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author Laing, Roz
Maitland, Kirsty
Lecová, Lenka
Skuce, Philip J.
Tait, Andy
Devaney, Eileen
author_facet Laing, Roz
Maitland, Kirsty
Lecová, Lenka
Skuce, Philip J.
Tait, Andy
Devaney, Eileen
author_sort Laing, Roz
collection PubMed
description Sheep farmers in the UK rely on strategic anthelmintic use to treat and control gastrointestinal roundworms in their flocks. However, resistance to these drugs is now widespread and threatens the sustainability of sheep production. The mechanisms underlying resistance to the most commonly used class, the macrocyclic lactones, are not known and sensitive diagnostic tools based on molecular markers are not currently available. This prohibits accurate surveillance of resistance or assessment of strategies aimed at controlling its spread. In this study, we examined four UK field populations of Haemonchus contortus, differing in macrocyclic lactone treatment history, for evidence of selection at ‘candidate gene’ loci identified as determining macrocyclic lactone resistance in previously published research. Individual worms were genotyped at Hc-lgc-37, Hc-glc-5, Hc-avr-14 and Hc-dyf-7, and four microsatellite loci. High levels of polymorphism were identified at the first three candidate gene loci with remarkably little polymorphism at Hc-dyf-7. While some between-population comparisons of individual farms with and without long-term macrocyclic lactone use identified statistically significant differences in allele frequency and/or fixation index at the Hc-lgc-37, Hc-glc-5 or Hc-avr-14 loci, we found no consistent evidence of selection in other equivalent comparisons. While it is possible that different mechanisms are important in different populations or that resistance may be conferred by small changes at multiple loci, our findings suggest that these are unlikely to be major loci conferring macrocyclic lactone resistance on UK farms or suitable for diagnostic marker development. More powerful approaches, using genome-wide or whole genome sequencing, may be required to define macrocyclic lactone resistance loci in such genetically variable populations.
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spelling pubmed-50114292016-09-14 Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use Laing, Roz Maitland, Kirsty Lecová, Lenka Skuce, Philip J. Tait, Andy Devaney, Eileen Int J Parasitol Article Sheep farmers in the UK rely on strategic anthelmintic use to treat and control gastrointestinal roundworms in their flocks. However, resistance to these drugs is now widespread and threatens the sustainability of sheep production. The mechanisms underlying resistance to the most commonly used class, the macrocyclic lactones, are not known and sensitive diagnostic tools based on molecular markers are not currently available. This prohibits accurate surveillance of resistance or assessment of strategies aimed at controlling its spread. In this study, we examined four UK field populations of Haemonchus contortus, differing in macrocyclic lactone treatment history, for evidence of selection at ‘candidate gene’ loci identified as determining macrocyclic lactone resistance in previously published research. Individual worms were genotyped at Hc-lgc-37, Hc-glc-5, Hc-avr-14 and Hc-dyf-7, and four microsatellite loci. High levels of polymorphism were identified at the first three candidate gene loci with remarkably little polymorphism at Hc-dyf-7. While some between-population comparisons of individual farms with and without long-term macrocyclic lactone use identified statistically significant differences in allele frequency and/or fixation index at the Hc-lgc-37, Hc-glc-5 or Hc-avr-14 loci, we found no consistent evidence of selection in other equivalent comparisons. While it is possible that different mechanisms are important in different populations or that resistance may be conferred by small changes at multiple loci, our findings suggest that these are unlikely to be major loci conferring macrocyclic lactone resistance on UK farms or suitable for diagnostic marker development. More powerful approaches, using genome-wide or whole genome sequencing, may be required to define macrocyclic lactone resistance loci in such genetically variable populations. Elsevier Science 2016-09 /pmc/articles/PMC5011429/ /pubmed/27179994 http://dx.doi.org/10.1016/j.ijpara.2016.03.010 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Laing, Roz
Maitland, Kirsty
Lecová, Lenka
Skuce, Philip J.
Tait, Andy
Devaney, Eileen
Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use
title Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use
title_full Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use
title_fullStr Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use
title_full_unstemmed Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use
title_short Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use
title_sort analysis of putative resistance gene loci in uk field populations of haemonchus contortus after 6 years of macrocyclic lactone use
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011429/
https://www.ncbi.nlm.nih.gov/pubmed/27179994
http://dx.doi.org/10.1016/j.ijpara.2016.03.010
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