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

Laing, R. , Maitland, K. , Lecova, L., Skuce, P. J., Tait, A. and Devaney, E. (2016) Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after six years of macrocyclic lactone use. International Journal for Parasitology, 46(10), pp. 621-630. (doi: 10.1016/j.ijpara.2016.03.010) (PMID:27179994) (PMCID:PMC5011429)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Lecova, Dr Lenka and Devaney, Professor Eileen and Tait, Professor Andy and Skuce, Dr Philip and Laing, Dr Roz and Maitland, Ms Kirsty
Authors: Laing, R., Maitland, K., Lecova, L., Skuce, P. J., Tait, A., and Devaney, E.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:International Journal for Parasitology
ISSN (Online):1879-0135
Published Online:11 May 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in International Journal for Parasitology 46(10): 621-630
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
636401The BUG consortium Building Upon the Genome: using H. contortus genomic resources to develop novel interventions to control endemic GI parasitesEileen DevaneyBiotechnology and Biological Sciences Research Council (BBSRC)BB/M003949/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED