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Multigenic architecture of piperaquine resistance trait in Plasmodium falciparum.
The Lancet Infectious Diseases ( IF 56.3 ) Pub Date : 2020-01-01 , DOI: 10.1016/s1473-3099(19)30689-9
Miguel Silva 1 , Carla Calçada 1 , Miguel Teixeira 1 , Maria Isabel Veiga 1 , Pedro Eduardo Ferreira 1
Affiliation  

William L Hamilton and colleagues and Rob W van der Pluijm and colleagues described the genomic evolution of Plasmodium falciparum malaria and the spread of resistance in this species to dihydroartemisinin–piperaquine in southeast Asia. Resistance in the region has been associated with crt polymorphisms, copy number variations in plasmepsins, and mdr1 genes. Despite compelling evidence regarding the determinant effect of crt polymorphisms on piperaquine resistance, the roles of plasmepsin variation and mdr1 genes, which were first identified in a 2017 phenotype–genotype association study, remain unclear. Therefore, we generated P falciparum Dd2 parasite lines with copy number variations in plasmepsin 2 or a hybrid of the plasmepsin 1 and plasmepsin 3 genes (plasmepsin 3–1) on a southeast-Asian genetic background to study the contribution of plasmepsins to piperaquine resistance ().

中文翻译:

恶性疟原虫的哌喹喹抗性状的多基因体系结构。

William L Hamilton及其同事和Rob W van der Pluijm及其同事描述了恶性疟原虫疟疾的基因组进化以及该物种对东南亚双氢青蒿素–哌喹的抗药性扩散。电阻在该区域已经与相关联的crt多态性,  , 拷贝数变异在plasmepsins, ,,  ,  ,  MDR1基因。, 尽管有充分的证据证明crt多态性对哌喹抗性具有决定性作用,但其仍是纤溶酶变异体和mdr1的作用。在2017年表型-基因型关联研究中首次发现的基因尚不清楚。因此,在东南亚遗传背景下,我们产生了恶性疟原虫2纤溶酶1纤溶酶3基因的混合体(纤溶酶3–1)中拷贝数变化的恶性疟原虫Dd2寄生品系,以研究纤溶酶对哌喹喹抗性的贡献( )。
更新日期:2019-12-25
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