Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta

Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic archite...

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Bibliographic Details
Published in:PLoS genetics 2017-06, Vol.13 (6), p.e1006857-e1006857
Main Authors: Choi, Young-Jun, Bisset, Stewart A, Doyle, Stephen R, Hallsworth-Pepin, Kymberlie, Martin, John, Grant, Warwick N, Mitreva, Makedonka
Format: Article
Language:English
Subjects:
Animals
Anthelmintic agents
Anthelmintics
Anthelmintics - therapeutic use
Bioinformatics
Biology and Life Sciences
Chemotherapy
Chromosome Mapping
Copy number
DNA Copy Number Variations - genetics
Dosage and administration
Drug resistance
Drug Resistance - genetics
Gene expression
Gene mapping
Gene polymorphism
Genes
Genetic aspects
Genomes
Genomics
Genotype
Grants
Health aspects
Humans
Inbreeding
Livestock
Medicine
Microbial drug resistance
Multidrug resistance
Parasites
Population
Regulatory sequences
Research and Analysis Methods
Roundworms
Sheep - parasitology
Soil sciences
Studies
Trichostrongyloidea - drug effects
Trichostrongyloidea - genetics
Trichostrongyloidea - pathogenicity
Trichostrongyloidiasis - drug therapy
Trichostrongyloidiasis - genetics
Trichostrongyloidiasis - parasitology
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Summary:Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic architecture of resistance is poorly understood for any nematode, we have analyzed multidrug resistant Teladorsagia circumcincta, a major parasite of sheep, as a model for analysis of resistance selection. We introgressed a field-derived multiresistant genotype into a partially inbred susceptible genetic background (through repeated backcrossing and drug selection) and performed genome-wide scans in the backcross progeny and drug-selected F2 populations to identify the major genes responsible for the multidrug resistance. We identified variation linking candidate resistance genes to each drug class. Putative mechanisms included target site polymorphism, changes in likely regulatory regions and copy number variation in efflux transporters. This work elucidates the genetic architecture of multiple anthelmintic resistance in a parasitic nematode for the first time and establishes a framework for future studies of anthelmintic resistance in nematode parasites of humans.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1006857