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A Whole Genome Re-Sequencing Based GWA Analysis Reveals Candidate Genes Associated with Ivermectin Resistance in Haemonchus contortus

文献类型： 外文期刊

作者： Khan, Sawar 1 ; Nisar, Ayesha 1 ; Yuan, Jianqi 1 ; Luo, Xiaoping 1 ; Dou, Xueqin 1 ; Liu, Fei 1 ; Zhao, Xiaochao 1 ; Li, 1 ;

作者机构： 1.Chinese Acad Agr Sci, Shanghai Vet Res Inst, Key Lab Anim Parasitol, Minist Agr China, Shanghai 200241, Peoples R China

2.Inner Mongolia Acad Agr & Anim Husb Sci, Vet Res Inst, Hohhot 010031, Peoples R China

3.Hazara Univ, Dept Genet, Mansehra 21300, Pakistan

4.Hazara Univ, Dept Zool, Mansehra 21300, Pakistan

关键词： Haemonchus contortus; population genomics; drug resistance; ivermectin; RNAi; functional validation; larvae culture

期刊名称：GENES （ 影响因子：4.096； 五年影响因子：4.339 ）

ISSN：

年卷期： 2020 年 11 卷 4 期

页码：

收录情况： SCI

摘要： The most important and broad-spectrum drug used to control the parasitic worms to date is ivermectin (IVM). Resistance against IVM has emerged in parasites, and preserving its efficacy is now becoming a serious issue. The parasitic nematode Haemonchus contortus (Rudolphi, 1803) is economically an important parasite of small ruminants across the globe, which has a successful track record in IVM resistance. There are growing evidences regarding the multigenic nature of IVM resistance, and although some genes have been proposed as candidates of IVM resistance using lower magnification of genome, the genetic basis of IVM resistance still remains poorly resolved. Using the full magnification of genome, we herein applied a population genomics approach to characterize genome-wide signatures of selection among pooled worms from two susceptible and six ivermectin-resistant isolates of H. contortus, and revealed candidate genes under selection in relation to IVM resistance. These candidates also included a previously known IVM-resistance-associated candidate gene HCON_00148840, glc-3. Finally, an RNA-interference-based functional validation assay revealed the HCON_00143950 as IVM-tolerance-associated gene in H. contortus. The possible role of this gene in IVM resistance could be detoxification of xenobiotic in phase I of xenobiotic metabolism. The results of this study further enhance our understanding on the IVM resistance and continue to provide further evidence in favor of multigenic nature of IVM resistance.

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