Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Nat Genet. 2010 Mar;42(3):268-71. doi: 10.1038/ng.528. Epub 2010 Jan 31.
Antimalarial drugs impose strong selective pressure on Plasmodium falciparum parasites and leave signatures of selection in the parasite genome; screening for genes under selection may suggest potential drug or immune targets. Genome-wide association studies (GWAS) of parasite traits have been hampered by the lack of high-throughput genotyping methods, inadequate knowledge of parasite population history and time-consuming adaptations of parasites to in vitro culture. Here we report the first Plasmodium GWAS, which included 189 culture-adapted P. falciparum parasites genotyped using a custom-built Affymetrix molecular inversion probe 3K malaria panel array with a coverage of approximately 1 SNP per 7 kb. Population structure, variation in recombination rate and loci under recent positive selection were detected. Parasite half-maximum inhibitory concentrations for seven antimalarial drugs were obtained and used in GWAS to identify genes associated with drug responses. This study provides valuable tools and insight into the P. falciparum genome.
抗疟药物对恶性疟原虫寄生虫施加了强烈的选择性压力，并在寄生虫基因组中留下了选择的痕迹；筛选受选择的基因可能提示潜在的药物或免疫靶标。寄生虫特征的全基因组关联研究（GWAS）受到缺乏高通量基因分型方法、寄生虫种群历史知识不足以及寄生虫对体外培养的耗时适应的阻碍。在这里，我们报告了第一个恶性疟原虫 GWAS，该研究包括使用定制的 Affymetrix 分子反转探针 3K 疟疾面板阵列对 189 株经培养适应的恶性疟原虫寄生虫进行基因分型，该阵列的覆盖率约为每 7 kb 有 1 个 SNP。检测到种群结构、重组率变异和近期正选择下的基因座。获得了七种抗疟药物的寄生虫半数最大抑制浓度，并用于 GWAS 以鉴定与药物反应相关的基因。这项研究为恶性疟原虫基因组提供了有价值的工具和见解。
