美国哈佛大学研究人员4月21日公布研究报告称，他们发现了11个与疟原虫产生耐药性有关的基因变异。
研究人员在美国《公共科学图书馆—遗传学》 PLoS Genetics 杂志网络版上报告说，他们分析了来自亚洲、非洲以及南美洲的57个已具有耐药性的恶性疟原虫的脱氧核糖核酸（DNA），筛查了1.7万多个基因变异，并测试了这些疟原虫对13种疟疾药的反应，最终确认了11个基因变异与疟原虫的耐药性有关。
参与研究的哈佛大学公共卫生学院研究人员莎拉·沃尔克曼表示，确认与耐药性有关的基因变异有助于理解疟原虫如何规避药物作用，并据此开发出抗疟疾新药，限制疟原虫这种能力。
疟疾是由疟原虫引起的疾病，通过蚊子叮咬传播，其症状包括发热、头痛、呕吐等，如不及时治疗可能危及生命。在世界很多地区，疟原虫已经对一些抗疟药物产生耐药性。据世界卫生组织统计，2009年全球有78.1万人死于疟疾，其中多数生活在撒哈拉沙漠以南的非洲地区。（生物谷Bioon.com）
生物谷推荐原文出处：
PLoS Genet 7(4): e1001383. doi:10.1371/journal.pgen.1001383
Identification and Functional Validation of the Novel Antimalarial Resistance Locus PF10_0355 in Plasmodium falciparum
Daria Van Tyne1#, Daniel J. Park2,3#, Stephen F. Schaffner2#, Daniel E. Neafsey2#, Elaine Angelino4,5#, Joseph F. Cortese2, Kayla G. Barnes1, David M. Rosen1, Amanda K. Lukens1, Rachel F. Daniels2,6, Danny A. Milner Jr.1, Charles A. Johnson2, Ilya Shlyakhter2,3,4, Sharon R. Grossman2,3,4,5, Justin S. Becker1, Daniel Yamins4, Elinor K. Karlsson2,3,4, Daouda Ndiaye7, Ousmane Sarr7, Souleymane Mboup7, Christian Happi8, Nicholas A. Furlotte9, Eleazar Eskin9, Hyun Min Kang10, Daniel L. Hartl3, Bruce
The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms (~1 SNP/kb), and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS), searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome.
