Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing

Redman, E., Sargison, N., Whitelaw, F., Jackson, F., Morrison, A., Bartley, D.J. and Gilleard, J. (2012) Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing. PLoS Pathogens, 8(2), e1002534. (doi: 10.1371/journal.ppat.1002534) (PMID:22359506) (PMCID:PMC3280990)

Abstract

Anthelmintic drug resistance in livestock parasites is already widespread and in recent years there has been an increasing level of anthelmintic drug selection pressure applied to parasitic nematode populations in humans leading to concerns regarding the emergence of resistance. However, most parasitic nematodes, particularly those of humans, are difficult experimental subjects making mechanistic studies of drug resistance extremely difficult. The small ruminant parasitic nematode Haemonchus contortus is a more amenable model system to study many aspects of parasite biology and investigate the basic mechanisms and genetics of anthelmintic drug resistance. Here we report the successful introgression of ivermectin resistance genes from two independent ivermectin resistant strains, MHco4(WRS) and MHco10(CAVR), into the susceptible genome reference strain MHco3(ISE) using a backcrossing approach. A panel of microsatellite markers were used to monitor the procedure. We demonstrated that after four rounds of backcrossing, worms that were phenotypically resistant to ivermectin had a similar genetic background to the susceptible reference strain based on the bulk genotyping with 18 microsatellite loci and individual genotyping with a sub-panel of 9 microsatellite loci. In addition, a single marker, Hcms8a20, showed evidence of genetic linkage to an ivermectin resistance-conferring locus providing a starting point for more detailed studies of this genomic region to identify the causal mutation(s). This work presents a novel genetic approach to study anthelmintic resistance and provides a “proof-of-concept” of the use of forward genetics in an important model strongylid parasite of relevance to human hookworms. The resulting strains provide valuable resources for candidate gene studies, whole genome approaches and for further genetic analysis to identify ivermectin resistance loci.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Redman, Dr Elizabeth and Gilleard, Professor John and Whitelaw, Miss Fiona
• Authors: Redman, E., Sargison, N., Whitelaw, F., Jackson, F., Morrison, A., Bartley, D.J., and Gilleard, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Published Online: 16 February 2012
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in PLoS Pathogens 8(2):e1002534
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
44388	1	Population genetics and genomics of ovine parasitic nematodes and their application to the study of anthelmintic resistance	Andrew Tait	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/E018505/1	School of Veterinary Medicine