抗青蒿素疟疾的一个标记

2014/01/06 21:37:02

青蒿素抗药性在所分离出的东南亚疟疾病原体“镰刀形疟原虫”中的传播，可能会葬送为在全世界根除这种疾病所作努力。监测抗药性这一重要工作一直受阻于缺少一个分子标记。现在，Frederic Ariey及同事识别出了“镰刀形疟原虫”青蒿素抗药性的一个主要决定因子，它也许能提供这样一个标记。他们发现，该寄生虫的PF3D7_1343700 kelch propeller domain 中发生的突变与抗药性最近的传播有关。与在2001年和2012年间收集的样本所作比较显示，与抗药性的传播相一致的是，该标记的频率也增加了。除了提出一个有用的标记外，这些发现还有可能加深我们对抗药性怎样形成的认识，同时为在寻找新型抗疟疾药物中怎样绕过抗药性提供思路。

PCR_Sequencing for genotyping SNPs PF3D7_1343700 Kelch protein propeller domain

doi:10.1038/protex.2013.096

Didier Menard & Frederic Ariey

Table 1: Primary and secondary forward (F) and reverse (R) PCR primers

Primer name	PCR	Sequence (5’–  3’)
K13_PCR_F	PCR	CGGAGTGACCAAATCTGGGA
K13_PCR_R		GGGAATCTGGTGGTAACAGC
K13_N1_F	Nested	GCCAAGCTGCCATTCATTTG
K13_N1_R		GCCTTGTTGAAAGAAGCAGA

Figure 1: PCR products for Nested PCR for PF3D7_1343700.

*S1: 3D7, S2-S16: tested samples, Neg: PCR negative controls

Figure 2:_ P. falciparum_ 3D7 protein coding gene on Pf3D7_13_v3 from 1,724,817 to 1,726,997 (Chromosome: 13)

*2181 bp sequences flanking candidate marker SNPs from 3D7 complete genome are given. Positions of primary primers (yellow) and secondary primers (green) are shown.

Figure 3: Polymorphisms observed in the K13-propeller domain

8. Appendix B. SNPs in PF3D7_1343700 Kelch protein propeller domain already observed

Colour code: dark grey Plasmodium-specific (positions 1-225) then Apicomplexa-specific (225-345), light grey: BTB/POZ domain The individual kelch domains are colour coded as in Figure 5 (see Ariey et al, Nature, 2013)