Genome-wide analysis of the response to ivermectin treatment by a Swedish field population of Haemonchus contortus.
Genome-wide analysis of the response to ivermectin treatment by a Swedish field population of Haemonchus contortus.
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DOI：
10.1016/j.ijpddr.2021.12.002
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Höglund J
中科院分区：
文献类型：
--
作者：
Baltrušis P;Doyle SR;Halvarsson P;Höglund J
弯曲血蜱是小型反刍动物的一种致病性胃肠道线虫，部分由于其产生耐药性的能力，在世界范围内造成动物生产部门的重大损失。尽管经过了几十年的研究，但对该物种对伊维菌素等药物产生耐药性的具体机制知之甚少。在这里，我们描述了一种全基因组方法，用于检测来自瑞典的田间种群中伊维菌素治疗的选择证据，使用伊维菌素暴露前和暴露后7天从同一动物中采集的寄生虫，然后进行全基因组测序。尽管通过粪卵计数减少试验测量，治疗后恢复的寄生虫减少了89%，但存活的种群在遗传上与治疗前的种群高度相似，这表明抗性可能随着时间的推移而进化，抗性等位基因存在于不同的单倍型上。成对基因和SNP频率比较表明，分化程度最高的是4号染色体的末端，而核苷酸多样性差异最显著的是5号染色体上的一个区域，此前报道该区域含有一个与伊维菌素耐药性有关的主要数量性状位点。这些数据为野外种群中伊维菌素选择的全基因组效应提供了新的见解，并证实了先前建立的数量性状位点在伊维菌素耐药性发展中的重要性。治疗前和治疗后的人群基因相似，尽管减少了89%。在chr4中发现成对基因和SNP频率分化。伊维菌素QTL区核苷酸多样性差异研究
Haemonchus contortus is a pathogenic gastrointestinal nematode of small ruminants and, in part due to its capacity to develop resistance to drugs, contributes to significant losses in the animal production sector worldwide. Despite decades of research, comparatively little is known about the specific mechanism(s) driving resistance to drugs such as ivermectin in this species. Here we describe a genome-wide approach to detect evidence of selection by ivermectin treatment in a field population of H. contortus from Sweden, using parasites sampled from the same animals before and seven days after ivermectin exposure followed by whole-genome sequencing. Despite an 89% reduction in parasites recovered after treatment measured by the fecal egg count reduction test, the surviving population was highly genetically similar to the population before treatment, suggesting that resistance has likely evolved over time and that resistance alleles are present on diverse haplotypes. Pairwise gene and SNP frequency comparisons indicated the highest degree of differentiation was found at the terminal end of chromosome 4, whereas the most striking difference in nucleotide diversity was observed in a region on chromosome 5 previously reported to harbor a major quantitative trait locus involved in ivermectin resistance. These data provide novel insight into the genome-wide effect of ivermectin selection in a field population as well as confirm the importance of the previously established quantitative trait locus in the development of resistance to ivermectin. Pre- and post-treatment populations were genetically similar despite 89% reduction. Pairwise gene and SNP frequency differentiation identified in chr4. Difference in nucleotide diversity found in ivermectin QTL region in chr5.
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影响因子：
4.5
作者：
Choi YJ;Bisset SA;Doyle SR;Hallsworth-Pepin K;Martin J;Grant WN;Mitreva M
通讯作者：
Mitreva M
影响因子：
10.7
作者：
Cheeseman IH;McDew-White M;Phyo AP;Sriprawat K;Nosten F;Anderson TJ
通讯作者：
Anderson TJ
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
6.7
作者：
Abkallo HM;Martinelli A;Inoue M;Ramaprasad A;Xangsayarath P;Gitaka J;Tang J;Yahata K;Zoungrana A;Mitaka H;Acharjee A;Datta PP;Hunt P;Carter R;Kaneko O;Mustonen V;Illingworth CJR;Pain A;Culleton R
通讯作者：
Culleton R
影响因子：
9.6
作者：
Anderson TJC;LoVerde PT;Le Clec'h W;Chevalier FD
通讯作者：
Chevalier FD