A survey of allelic imbalance in F1 mice
A survey of allelic imbalance in F1 mice
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DOI：
10.1101/gr.068692.107
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发表时间：
2008-04-01
期刊：
影响因子：
7
通讯作者：
Hirschhorn, Joel N.
中科院分区：
文献类型：
--
作者：
Campbell, Catarina D.;Kirby, Andrew;Hirschhorn, Joel N.
基因表达存在广泛的、由遗传决定的差异。然而，比较个体之间转录水平的方法受到反式作用效应和环境差异的影响。通过观察近交系小鼠F1代的等位基因特异性表达，我们可以直接检测等位基因不平衡（AI），这一定是由于亲本品系中的顺式作用变体。我们在F1小鼠中测试了C57 BI/6 J和A/J等位基因之间的100多个AI基因，包括富含顺式作用变体的23个基因的验证集和第二组92个基因，其直系同源物先前在人类中进行了AI检查。我们分析了平均两个转录单核苷酸多态性每个基因在肝脏，脾脏和大脑从三个男性和三个女性的F1小鼠。在92个基因中，我们观察到33个基因（36%）具有显著的AI，包括特定于某些组织或转录本的AI基因。我们还观察到广泛的组织特异性AI，92个基因中有11个（12%）在组织之间的AI存在差异。有趣的是，几个具有交替转录本的基因具有转录本特异性AI。最后，我们观察到人类基因中AI的存在与小鼠直系同源物中AI的存在相关（单尾P = 0.003），这表明某些基因可能更耐受跨物种的顺式作用变异。
There are widespread, genetically determined differences in gene expression. However, methods that compare transcript levels between individuals are subject to trans-acting effects and environmental differences. By looking at allele-specific expression in the F1 progeny of inbred mice, we can directly test for allelic imbalance (AI), which must be due to cis-acting variants in the parental strains. We tested over one hundred genes for AI between C57BI/6J and A/J alleles in F1 mice, including a validation set of 23 genes enriched for cis-acting variants and a second set of 92 genes whose orthologs were previously examined for AI in humans. We assayed an average of two transcribed SNPs per gene in liver, spleen, and brain from three male and three female F1 mice. In the set of 92 genes, we observed 33 genes (36%) with significant AI including genes with AI that was specific to certain tissues or transcripts. We also observed extensive tissue-specific AI, with 11 out of 92 genes (12%) having differences in AI between tissues. Interestingly, several genes with alternate transcripts have transcript-specific AI. Finally, we observed that the presence of AI in human genes was correlated to the presence of AI in the mouse orthologs (one-tailed P = 0.003), suggesting that certain genes may be more tolerant of cis-acting variation across species.