Haplotype diversity and linkage disequilibrium at human G6PD:: Recent origin of alleles that confer malarial resistance
Haplotype diversity and linkage disequilibrium at human G6PD:: Recent origin of alleles that confer malarial resistance
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DOI：
10.1126/science.1061573
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发表时间：
2001-07-20
期刊：
影响因子：
56.9
通讯作者：
Clark, AG
中科院分区：
文献类型：
--
作者：
Tishkoff, SA;Varkonyi, R;Clark, AG
人葡萄糖-6-磷酸脱氢酶低活性等位基因的频率与疟疾的流行高度相关。这些“缺陷”等位基因被认为降低了疟原虫寄生虫感染的风险，并且尽管它们引起血液病理学，但仍保持高频率。在这个位点上的“A-”和“Med”突变的单倍型分析表明，它们已经独立进化，并且频率以太快的速度增加，以至于不能用随机遗传漂变来解释。统计模型表明，A-等位基因出现在过去的3840年至11,760年，而Med等位基因出现在过去的1600年至6640年。这些结果支持了这样一个假设，即疟疾只是在过去10，000年内引入农业之后才对人类产生重大影响，并提供了人类基因组选择特征的一个引人注目的例子。
The frequencies of Low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite the hemopathologies that they cause. Haplotype analysis of "A-" and "Med" mutations at this Locus indicates that they have evolved independently and have increased in frequency at a rate that is too rapid to be explained by random genetic drift. Statistical modeling indicates that the A- allele arose within the past 3840 to 11,760 years and the Med allele arose within the past 1600 to 6640 years. These results support the hypothesis that malaria has had a major impact on humans only since the introduction of agriculture within the past 10,000 years and provide a striking example of the signature of selection on the human genome.