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

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 parasi...

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Autores principales:	Elizabeth Redman, Neil Sargison, Fiona Whitelaw, Frank Jackson, Alison Morrison, David Jon Bartley, John Stuart Gilleard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/509c5eb8b7484e06af2392cff4d0b0f4
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spelling	oai:doaj.org-article:509c5eb8b7484e06af2392cff4d0b0f42021-11-18T06:04:45ZIntrogression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing.1553-73661553-737410.1371/journal.ppat.1002534https://doaj.org/article/509c5eb8b7484e06af2392cff4d0b0f42012-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22359506/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Anthelmintic 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.Elizabeth RedmanNeil SargisonFiona WhitelawFrank JacksonAlison MorrisonDavid Jon BartleyJohn Stuart GilleardPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 2, p e1002534 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Elizabeth Redman Neil Sargison Fiona Whitelaw Frank Jackson Alison Morrison David Jon Bartley John Stuart Gilleard Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing.
description	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.
format	article
author	Elizabeth Redman Neil Sargison Fiona Whitelaw Frank Jackson Alison Morrison David Jon Bartley John Stuart Gilleard
author_facet	Elizabeth Redman Neil Sargison Fiona Whitelaw Frank Jackson Alison Morrison David Jon Bartley John Stuart Gilleard
author_sort	Elizabeth Redman
title	Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing.
title_short	Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing.
title_full	Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing.
title_fullStr	Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing.
title_full_unstemmed	Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing.
title_sort	introgression of ivermectin resistance genes into a susceptible haemonchus contortus strain by multiple backcrossing.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/509c5eb8b7484e06af2392cff4d0b0f4
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Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing.

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