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

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posted on 2023-04-26, 06:23 authored by Young-Jun Choi, Stewart A Bisset, Stephen R Doyle, Kymberlie Hallsworth-Pepin, John Martin, Warwick GrantWarwick Grant, Makedonka Mitreva

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.

History

Publication Date

2017-06-23

Journal

PLOS Genetics

Volume

13

Issue

6

Article Number

e1006857

Pagination

31p.

Publisher

Public Library of Science

ISSN

1553-7404

Rights Statement

© 2017 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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