Science：研究解析东南亚抗药性疟疾的根源

4月6日，国际著名杂志Science在线刊登了国外研究人员的最新研究成果“A Major Genome Region Underlying Artemisinin Resistance in Malaria，”，在文章中，研究人员在恶性疟原虫（这是一种主要的疟疾寄生虫）的某个染色体上发现了一个特定区域，该区域可帮助解释这种在东南亚的寄生虫是如何对目前这一代的以青蒿素为基础的药物产生抗药性的。

目前，以青蒿素为基础的组合疗法几乎代表了所有疟疾流行国家中的第一线的治疗方法。但是，对这些治疗的抗药性的出现最近已经在柬埔寨西部和泰国西部得到证实。这一“治疗延迟”意味着在该地区的以青蒿素为基础的治疗从宿主体内清除疟原虫的速度要比其它地区缓慢。

因此，Ian Cheeseman及其同事们对取自那2个国家及老挝的91个恶性虐原虫的基因组进行了测序，在老挝，对最新的以青蒿素为基础的药物的抗药性还没有出现。在分析了结果之后，他们发现恶性虐原虫基因组的33个区域似乎受到了青蒿素耐药性的强力选择。在进行更为仔细的观察之后，研究人员能够将这一热点的范围缩窄至遍及35,000个碱基对的第13号染色体上的7个特定的基因。据Cheeseman及其同事们披露，这一特定的染色体部分可解释所观察到的恶性虐原虫在东南亚清除速率降低现象中的35%。研究人员还注意到，13号染色体上的这些基因中有3个基因会根据寄生虫进入何种生命周期的阶段而有不同的表达。（生物谷Bioon.com）

doi:10.1126/science.1215966
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A Major Genome Region Underlying Artemisinin Resistance in Malaria

Ian H. Cheeseman1, Becky A. Miller2, Shalini Nair1, Standwell Nkhoma1, Asako Tan2, John C. Tan2, Salma Al Saai1, Aung Pyae Phyo3, Carit Ler Moo3, Khin Maung Lwin3, Rose McGready3,4,5, Elizabeth Ashley3,4,5, Mallika Imwong4, Kasia Stepniewska4,5,7, Poravuth Yi8, Arjen M. Dondorp4,5, Mayfong Mayxay6, Paul N. Newton5,6, Nicholas J. White4,5, François Nosten3,4,5, Michael T. Ferdig2, Timothy J. C. Anderson1,*

Evolving resistance to artemisinin-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10−6 to 10−12) with slow CRs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits.