Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection
Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection
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DOI：
10.1086/421330
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发表时间：
2004-06-01
影响因子：
9.8
通讯作者：
Tokunaga, K
中科院分区：
文献类型：
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作者：
Ohashi, J;Naka, I;Tokunaga, K
血红蛋白E变体（HbE; (β)26Glu- >Lys）集中在疟疾流行的东南亚部分地区，HbE携带者已被证明对恶性疟原虫疟疾具有一定的保护作用。为了研究自然选择对连锁不平衡（LD）模式的影响，并推断HbE变体的进化史，我们分析了泰国人群中HbE变体周围的双等位基因标记。对HbE和43个周围双等位基因标记进行的双等位基因分析显示，HbE的遗传变异长度超过100 kb，而非HbE变异与相同标记之间没有遗传变异。推断的单倍型网络表明泰国人群中HbE变体的单一起源。在各种选择模型下进行的时间前计算机模拟表明，HbE变体出现在1240 - 4440年前。这些结果支持了HbE突变发生时间较近且等位基因频率增加较快的推测。我们的研究提供了另一个清晰的证据，即人类基因组的高分辨率LD图可以检测到最近受到正选择的变异。
The hemoglobin E variant (HbE; (beta)26Glu-->Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240-4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.