Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome
Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome
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DOI：
10.1038/ng1924
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发表时间：
2007-01-01
期刊：
影响因子：
30.8
通讯作者：
Su, Xin-zhuan
中科院分区：
文献类型：
--
作者：
Mu, Jianbing;Awadalla, Philip;Su, Xin-zhuan
恶性疟原虫基因组测序的一个目标是发现疫苗和药物靶标(1)。恶性疟原虫是最致命的疟疾形式的病原体。然而，在基因组中识别这些靶点是一个巨大的挑战，在基因组中，大约60%的基因具有未知的功能。由于大多数已知的疟疾抗原和耐药基因是高度多态的，并在不同的选择压力(2-6)下，全基因组分析选择的特征可能导致发现新的候选疫苗和药物。在这里，我们调查了3539个恶性疟原虫基因(与预测基因的65%相似)的多态，并确定了各种高度多态的基因座和基因，其中一些编码新的抗原，我们用人免疫血清证实了这一点。我们收集的全基因组SNPs(类似于65%的非同义)以及多态微卫星和INDELs为绘制寄生虫特征和研究寄生虫种群提供了高分辨率的图谱(每个类似4kb的标记一个)。此外，我们还报告了新的抗原，为疾病控制提供了急需的候选疫苗。
One goal in sequencing the Plasmodium falciparum genome, the agent of the most lethal form of malaria, is to discover vaccine and drug targets(1). However, identifying those targets in a genome in which similar to 60% of genes have unknown functions is an enormous challenge. Because the majority of known malaria antigens and drug-resistant genes are highly polymorphic and under various selective pressures(2-6), genome-wide analysis for signatures of selection may lead to discovery of new vaccine and drug candidates. Here we surveyed 3,539 P. falciparum genes (similar to 65% of the predicted genes) for polymorphisms and identified various highly polymorphic loci and genes, some of which encode new antigens that we confirmed using human immune sera. Our collections of genome-wide SNPs (similar to 65% nonsynonymous) and polymorphic microsatellites and indels provide a high-resolution map (one marker per similar to 4 kb) for mapping parasite traits and studying parasite populations. In addition, we report new antigens, providing urgently needed vaccine candidates for disease control.