Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Department of Biomedical Sciences, University of Cape Coast, Cape Coast, Ghana.
Nat Commun. 2023 Aug 16;14(1):4946. doi: 10.1038/s41467-023-40693-0.
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.
对杀虫剂的抗药性威胁到疟疾控制的有效性，但对其抗药性的遗传学了解还只是部分的。我们对来自西非十个地点的冈比亚按蚊和库蚊进行了大规模的多国全基因组关联研究，以研究对两种广泛使用的杀虫剂：溴氰菊酯和丙溴磷的抗药性。抗药性具有高度的多基因、多等位基因和种群间的变异性。虽然与溴氰菊酯抗药性最强和最一致的关联来自 Cyp6aa1，但这是基于在安·库鲁齐的几个独立的拷贝数变异（CNVs），以及在冈比亚按蚊的非 CNV 单倍型。对于丙溴磷，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 nAChR 靶位。Cyp9k1 和 Tep 家族免疫基因周围的区域显示出对这两种杀虫剂的交叉抗药性的证据。这些局部变化、多等位基因的模式突出了基因组监测抗药性所涉及的挑战，并且可能为改进的监测方法奠定基础。
