Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae s.l.
Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae s.l.
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全基因组关联研究揭示了冈比亚按蚊 s.l 中与拟除虫菊酯和有机磷抗性相关的新位点。
DOI：
10.1101/2023.01.13.523889
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hard
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文献类型：
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作者：
Lucas,EricR;Nagi,SanjayC;Egyir-Yawson,Alexander;Essandoh,John;Dadzie,Sam;Chabi,Joseph;Djogbénou,LucS;Medjigbodo,AdandéA;Edi,ConstantV;Ketoh,GuillaumeK;Koudou,BenjaminG;Van'tHof,ArjenE;Rippon,EmilyJ;Pipini,Dimitra;Hard
蚊子对杀虫剂的抗药性威胁着疟疾控制的有效性，但对抗药性的遗传学只有部分了解。我们利用弗罗曼的测序数据，对两种广泛使用的杀虫剂：溴氰菊酯和甲基嘧啶磷进行了大规模的多个国家全基因组关联研究。冈比亚和An.来自西非的十个地点的可口可乐。抗性具有高度多基因、多等位基因和居群间变异的特点。虽然与溴氰菊酯抗性最强烈和最一致的关联来自Cyp6aa1，但这是基于ANN中几个独立的拷贝数变体(CNV)。Coluzzii和非CNV单倍型Inan。冈比亚亚目。甲基嘧啶磷信号包括Ace1、细胞色素P450s、谷胱甘肽S转移酶和新烟碱类杀虫剂的AChR靶位。Cyp9k1和免疫基因Tep族周围的区域显示出对这两种杀虫剂的交叉抗药性。这些局部变异的多等位基因模式突出了基因组监测抗药性所涉及的挑战，并可能形成改进监测方法的基础。
Resistance to insecticides inAnophelesmosquitoes 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 fromAn. gambiaeandAn. coluzziifrom 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 fromCyp6aa1, this was based on several independent copy number variants (CNVs) inAn. coluzzii, and on a non-CNV haplotype inAn. gambiae. For pirimiphos-methyl, signals includedAce1, cytochrome P450s, glutathione S-transferases and thenAChRtarget site of neonicotinoid insecticides. The regions aroundCyp9k1and theTepfamily 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.