Allelic variation in human gene expression
Allelic variation in human gene expression
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DOI：
10.1126/science.1072545
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发表时间：
2002-08-16
期刊：
影响因子：
56.9
通讯作者：
Kinzler, KW
中科院分区：
文献类型：
--
作者：
Yan, H;Yuan, WS;Kinzler, KW
了解人类变异的遗传基础是生物医学研究的一个重要目标。对其他生物的研究表明，基因表达水平的差异是物种内和物种间变异的主要原因（1，2）。为了解决这一问题，在人类中，我们开发了方法来定量评估等位基因变异的基因expression.The基因表达变异的分析是复杂的潜在的小差异与单个等位基因的改变，以及由环境或生理，而不是遗传因素引起的个体之间的潜在变化。为了避免这些分析问题，我们比较了同一细胞样品中同一基因的两个等位基因的相对表达水平。为了进行这些比较，我们使用了基于荧光双脱氧终止子的方法（3）来区分等位基因的mRNA产物与目标转录本中单核苷酸多态性（SNP）杂合的正常个体（图S1）。我们估计，当两个等位基因的表达差异超过20%时，这种方法可以可靠地识别变异（3）。
Understanding the genetic basis of human variation is a vital goal of biomedical research. Studies in other organisms suggest that differences in gene expression levels account for a major part of the variation within and among species (1, 2). To address this in humans, we developed methods to quantitatively evaluate allelic variation in gene expression.The analysis of variation in gene expression is complicated by the potentially small differences associated with alterations in a single allele as well as by potential variations between individuals that arise from environmental or physiological rather than genetic factors. To circumvent these analytic problems, we compared the relative expression levels of two alleles of the same gene within the same cellular sample. To make these comparisons, we used a fluorescent dideoxy terminator–based method (3) to distinguish the mRNA products of alleles from normal individuals who were heterozygous for a single nucleotide polymorphism (SNP) in the transcript of interest (fig. S1). We estimated that this approach could confidently identify variations when the differences between expression of the two alleles differed by more than 20%(3).