Detection of regulatory variation in mouse genes
Detection of regulatory variation in mouse genes
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DOI：
10.1038/ng992
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发表时间：
2002-11-01
期刊：
影响因子：
30.8
通讯作者：
Lander, ES
中科院分区：
文献类型：
--
作者：
Cowles, CR;Hirschhorn, JN;Lander, ES
基因的功能多态性可分为编码变异（coding variation）和调控变异（regulatory variation），前者改变了编码蛋白的氨基酸序列，后者影响了基因表达的水平或模式。编码变异可以直接从DNA序列中识别出来，因此其频率和特征已经得到了广泛的描述。相比之下，人们对基因调控在种群中的变化程度几乎一无所知。然而，调控变异体在调节基因功能方面很可能是重要的：基因调控的改变已被提出影响疾病易感性，并已成为物种进化的主要基础(1)。在这里，我们报告了一项系统研究，以评估四个近交小鼠品系中69个基因的顺式作用调控变异程度。我们发现这些基因中至少有四个在表达水平上表现出1.5倍或更高的等位基因差异，其中一些差异是组织特异性的。结果表明，调控变异的影响可以在基因组调查中以显著的频率检测到，并表明这种变异可能对生物体表型和进化产生重要影响。结果表明，在小鼠和人类中进行更大规模的调查可以鉴定出大量具有共同调控变异的基因。
Functional polymorphism in genes can be classified as coding variation, altering the amino-acid sequence of the encoded protein, or regulatory variation, affecting the level or pattern of expression of the gene. Coding variation can be recognized directly from DNA sequence, and consequently its frequency and characteristics have been extensively described. By contrast, virtually nothing is known about the extent to which gene regulation varies in populations. Yet it is likely that regulatory variants are important in modulating gene function: alterations in gene regulation have been proposed to influence disease susceptibility and to have been the primary substrate for the evolution of species(1). Here, we report a systematic study to assess the extent of cis-acting regulatory variation in 69 genes across four inbred mouse strains. We find that at least four of these genes show allelic differences in expression level of 1.5-fold or greater, and that some of these differences are tissue specific. The results show that the impact of regulatory variants can be detected at a significant frequency in a genomic survey and suggest that such variation may have important consequences for organismal phenotype and evolution. The results indicate that larger-scale surveys in both mouse and human could identify a substantial number of genes with common regulatory variation.