Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii.

Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii.
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DOI:
10.1038/s41467-023-40693-0
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发表时间:
2023-08-16
影响因子:
16.6
通讯作者:
Weetman, David
Weetman, David
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lucas, Eric R.;Nagi, Sanjay C.;Egyir-Yawson, Alexander;Essandoh, John;Dadzie, Samuel;Chabi, Joseph;Djogbenou, Luc S.;Medjigbodo, Adande A.;Edi, Constant V.;Ketoh, Guillaume K.;Koudou, Benjamin G.;Van't Hof, Arjen E.;Rippon, Emily J.;Pipini, Dimitra;Harding, Nicholas J.;Dyer, Naomi A.;Cerdeira, Louise T.;Clarkson, Chris S.;Kwiatkowski, Dominic P.;Miles, Alistair;Donnelly, Martin J.;Weetman, David

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按蚊对杀虫剂的耐药性威胁着疟疾控制的有效性,但耐药性的遗传学仅得到部分了解。我们进行了一项大规模的多国全基因组关联研究,对两种广泛使用的杀虫剂:溴氰菊酯和甲基嘧啶的抗性,使用来自An. gambiae和An.来自西非十个地方的小浣熊抗性是高度多基因,多等位基因和变量之间的群体。虽然与溴氰菊酯抗性的最强和最一致的关联来自Cyp 6aa 1,但这是基于An中的几个独立拷贝数变体(CNV)。coluzzii的非CNV单倍型,以及An.冈比亚。对于甲基嘧啶,信号包括Ace 1、细胞色素P450、谷胱甘肽S-转移酶和烟碱类杀虫剂的nAChR靶位点。Cyp 9 k1和Tep家族免疫基因周围的区域显示出对两种杀虫剂交叉抗性的证据。这些局部变化的多等位基因模式突出了抗性基因组监测所涉及的挑战,并可能形成改进监测方法的基础。蚊子的抗药性对疟疾控制方案的成功构成威胁。这项研究发现,在西非不同种群的一种疟疾蚊子中,抗药性与不同的基因或同一组基因中的不同突变有关。
Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An. coluzzii from ten locations in West Africa. Resistance was highly multi-genic, multi-allelic and variable between populations. While the strongest and most consistent association with deltamethrin resistance came from Cyp6aa1, this was based on several independent copy number variants (CNVs) in An. coluzzii, and on a non-CNV haplotype in An. gambiae. For pirimiphos-methyl, signals included Ace1, cytochrome P450s, glutathione S-transferases and the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes showed evidence of cross-resistance to both insecticides. These locally-varying, multi-allelic patterns highlight the challenges involved in genomic monitoring of resistance, and may form the basis for improved surveillance methods. Insecticide resistance in mosquitoes threatens the success of malaria control programmes. This study found that in different populations of a malaria mosquito species in West Africa, resistance is associated with different genes or different mutations in the same set of genes.
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