Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.

The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assemb...

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Main Authors: Jennifer McIntyre, Alison Morrison, Kirsty Maitland, Duncan Berger, Daniel R G Price, Sam Dougan, Dionysis Grigoriadis, Alan Tracey, Nancy Holroyd, Katie Bull, Hannah Rose Vineer, Mike J Glover, Eric R Morgan, Alasdair J Nisbet, Tom N McNeilly, Yvonne Bartley, Neil Sargison, Dave Bartley, Matt Berriman, James A Cotton, Eileen Devaney, Roz Laing, Stephen R Doyle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-02-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1012820
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author Jennifer McIntyre
Alison Morrison
Kirsty Maitland
Duncan Berger
Daniel R G Price
Sam Dougan
Dionysis Grigoriadis
Alan Tracey
Nancy Holroyd
Katie Bull
Hannah Rose Vineer
Mike J Glover
Eric R Morgan
Alasdair J Nisbet
Tom N McNeilly
Yvonne Bartley
Neil Sargison
Dave Bartley
Matt Berriman
James A Cotton
Eileen Devaney
Roz Laing
Stephen R Doyle
author_facet Jennifer McIntyre
Alison Morrison
Kirsty Maitland
Duncan Berger
Daniel R G Price
Sam Dougan
Dionysis Grigoriadis
Alan Tracey
Nancy Holroyd
Katie Bull
Hannah Rose Vineer
Mike J Glover
Eric R Morgan
Alasdair J Nisbet
Tom N McNeilly
Yvonne Bartley
Neil Sargison
Dave Bartley
Matt Berriman
James A Cotton
Eileen Devaney
Roz Laing
Stephen R Doyle
author_sort Jennifer McIntyre
collection DOAJ
description The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, total scaffolds = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identifying key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control.
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spelling doaj-art-629e9eaaa18649c9aea62717b4e8519e2025-02-12T05:30:44ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-02-01212e101282010.1371/journal.ppat.1012820Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.Jennifer McIntyreAlison MorrisonKirsty MaitlandDuncan BergerDaniel R G PriceSam DouganDionysis GrigoriadisAlan TraceyNancy HolroydKatie BullHannah Rose VineerMike J GloverEric R MorganAlasdair J NisbetTom N McNeillyYvonne BartleyNeil SargisonDave BartleyMatt BerrimanJames A CottonEileen DevaneyRoz LaingStephen R DoyleThe parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, total scaffolds = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identifying key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control.https://doi.org/10.1371/journal.ppat.1012820
spellingShingle Jennifer McIntyre
Alison Morrison
Kirsty Maitland
Duncan Berger
Daniel R G Price
Sam Dougan
Dionysis Grigoriadis
Alan Tracey
Nancy Holroyd
Katie Bull
Hannah Rose Vineer
Mike J Glover
Eric R Morgan
Alasdair J Nisbet
Tom N McNeilly
Yvonne Bartley
Neil Sargison
Dave Bartley
Matt Berriman
James A Cotton
Eileen Devaney
Roz Laing
Stephen R Doyle
Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.
PLoS Pathogens
title Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.
title_full Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.
title_fullStr Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.
title_full_unstemmed Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.
title_short Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.
title_sort chromosomal genome assembly resolves drug resistance loci in the parasitic nematode teladorsagia circumcincta
url https://doi.org/10.1371/journal.ppat.1012820
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