A high throughput multi-locus insecticide resistance marker panel for tracking resistance emergence and spread in Anopheles gambiae
A high throughput multi-locus insecticide resistance marker panel for tracking resistance emergence and spread in Anopheles gambiae
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DOI：
10.1038/s41598-019-49892-6
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发表时间：
2019-09-16
影响因子：
4.6
通讯作者：
Donnelly, Martin J.
中科院分区：
文献类型：
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作者：
Lucas, Eric R.;Rockett, Kirk A.;Donnelly, Martin J.
对杀虫剂的抗药性在携带疾病的蚊子中的传播对控制方案的有效性构成了威胁，控制方案在很大程度上依赖于基于杀虫剂的干预措施。监测蚊子种群是必不可少的，但获得抗药性的表型测量既费力又容易出错。高通量基因分型提供了快速和可重复的抗药性估计的前景，同时也允许跟踪和研究抗药性标记。为了证明高度复合的基因筛查用于测量突变的抗药性关联并跟踪其传播的潜力，我们在主要疟疾媒介冈比亚按蚊中开发了一组28个已知或推定的抗药性标记，我们用它们来筛选来自撒哈拉以南非洲大片地区(布基纳法索、加纳、刚果民主共和国和肯尼亚)的蚊子。我们在四个标记中发现了抗性关联，包括解毒基因GSTe2(GSTe2-119V)的一个新突变。我们还在GSTe2中发现了一个复制，将与抗药性相关的突变与其野生型对应的突变结合在一起，潜在地减轻了抗药性的成本。最后，我们描述了kdr抗性的多重来源的分布，在刚果民主共和国发现了前所未有的多样性。该小组代表了向杀虫剂抗性定量基因模型迈出的第一步，该模型可用于预测蚊虫的抗性状态。冈比亚亚目。
The spread of resistance to insecticides in disease-carrying mosquitoes poses a threat to the effectiveness of control programmes, which rely largely on insecticide-based interventions. Monitoring mosquito populations is essential, but obtaining phenotypic measurements of resistance is laborious and error-prone. High-throughput genotyping offers the prospect of quick and repeatable estimates of resistance, while also allowing resistance markers to be tracked and studied. To demonstrate the potential of highly-mulitplexed genotypic screening for measuring resistance-association of mutations and tracking their spread, we developed a panel of 28 known or putative resistance markers in the major malaria vector Anopheles gambiae, which we used to screen mosquitoes from a wide swathe of Sub-Saharan Africa (Burkina Faso, Ghana, Democratic Republic of Congo (DRC) and Kenya). We found resistance association in four markers, including a novel mutation in the detoxification gene Gste2 (Gste2-119V). We also identified a duplication in Gste2 combining a resistance-associated mutation with its wild-type counterpart, potentially alleviating the costs of resistance. Finally, we describe the distribution of the multiple origins of kdr resistance, finding unprecedented diversity in the DRC. This panel represents the first step towards a quantitative genotypic model of insecticide resistance that can be used to predict resistance status in An. gambiae.