Cis-acting variation in the expression of a high proportion of genes in human brain
Cis-acting variation in the expression of a high proportion of genes in human brain
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DOI：
10.1007/s00439-003-0956-y
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发表时间：
2003-07-01
期刊：
影响因子：
5.3
通讯作者：
O'Donovan, MC
中科院分区：
文献类型：
--
作者：
Bray, NJ;Buckland, PR;O'Donovan, MC
人类表型多样性的许多遗传组成部分，包括对疾病的易感性，被认为是顺式作用对基因表达的影响的结果。如果这一假设是正确的，这意味着顺式作用的调控变异是一种普遍现象。然而，支持这一观点的直接证据很少。我们已经应用了高度定量的等位基因特异性表达的措施，以筛选平均19个信息主题（范围8-26）的存在下，共同的顺式作用的影响，通过使用来自人脑的RNA的15个基因的表达。我们发现，在15个测定基因中的7个中，至少一个个体表现出20%或更多的等位基因表达的相对差异，并且在一个基因（DTNBP 1）中，等位基因表达差异超过50%。这些结果表明，顺式作用的基因表达的变化通常发生在天然组织，因此提供经验支持的假设，这是潜在的一个重要机制，人类表型多样性。
Much of the genetic component of human phenotypic diversity, including susceptibility to disease, is proposed to be the result of cis-acting influences on gene expression. If this hypothesis is correct, it implies that cis-acting regulatory variation is a common phenomenon. However, direct evidence in support of this view is scarce. We have applied highly quantitative measures of allele-specific expression in order to screen an average of 19 informative subjects (range 8-26) for the presence of common cis-acting influences on the expression of 15 genes by using RNA derived from human brain. We found that, in seven of the 15 assayed genes, at least one individual exhibited relative differences in allelic expression of 20% or more and, in one gene (DTNBP1), allelic expression differences exceeded 50%. These results suggest that cis-acting variation in gene expression commonly occurs in native tissue and hence provide empirical support for the hypothesis that this is potentially an important mechanism underlying human phenotypic diversity.