Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human.
Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human.
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DOI：
10.1038/nmeth.1357
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发表时间：
2009-08
期刊：
影响因子：
48
通讯作者：
Church, George M.
中科院分区：
文献类型：
--
作者：
Zhang, Kun;Li, Jin Billy;Gao, Yuan;Egli, Dieter;Xie, Bin;Deng, Jie;Li, Zhe;Lee, Je-Hyuk;Aach, John;Leproust, Emily M.;Eggan, Kevin;Church, George M.
我们开发了一种数字RNA等位基因分型方法，用于定量探究等位基因特异性基因表达。该方法涉及对从转录组中锁式探针捕获的单核苷酸多态性（SNP）进行超高深度测序。我们对来自个人基因组计划中的两名人类受试者建立的四种细胞系进行了特征分析。在每种细胞系中，大约11 - 22%的与杂合mRNA相关的SNP显示出等位基因特异性表达；并且4.3 - 8.5%是组织特异性的，这表明存在组织特异性的顺式调控。当应用于两对同胞人类胚胎干细胞系时，同胞细胞系在等位基因特异性表达上比无遗传关系的细胞系更为相似。我们发现，不同细胞系之间基因表达中等位基因比例的变化主要由遗传变异解释，远比由特定组织类型或培养条件解释的程度要高。对正义链和反义链转录本上表达的SNP进行比较表明，等位基因比例主要由正义链转录本上的顺式调控机制决定。
We developed a digital RNA allelotyping method for quantitatively interrogating allele-specific gene expression. This method involves ultra-deep sequencing of padlock captured SNPs from the transcriptome. We characterized four cell lines established from two human subjects in the Personal Genome Project. Approximately 11–22% of the heterozygous mRNA-associated SNPs show allele-specific expression in each cell line; and 4.3–8.5% are tissue-specific, suggesting the presence of tissue-specific cis-regulation. When applied to two pairs of sibling human embryonic stem cell lines, the sibling lines were more similar in allele-specific expression than were the genetically unrelated lines. We found that the variation of allelic ratios in gene expression among different cell lines is primarily explained by genetic variations, much more so than by specific tissue types or culturing conditions. Comparison of expressed SNPs on the sense and anti-sense transcripts suggested that allelic ratios are primarily determined by cis-regulatory mechanisms on the sense transcripts.
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影响因子：
46.9
作者：
Deng, Jie;Shoemaker, Robert;Xie, Bin;Gore, Athurva;LeProust, Emily M.;Antosiewicz-Bourget, Jessica;Egli, Dieter;Maherali, Nimet;Park, In-Hyun;Yu, Junying;Daley, George Q.;Eggan, Kevin;Hochedlinger, Konrad;Thomson, James;Wang, Wei;Gao, Yuan;Zhang, Kun
通讯作者：
Zhang, Kun
影响因子：
7
作者：
Milani, Lili;Lundmark, Anders;Syvanen, Ann-Christine
通讯作者：
Syvanen, Ann-Christine
影响因子：
5.2
作者：
Hoffman, LM;Hall, L;Carpenter, MK
通讯作者：
Carpenter, MK
影响因子：
7
作者：
Bjornsson, Hans T.;Albert, Thomas J.;Feinberg, Andrew P.
通讯作者：
Feinberg, Andrew P.
影响因子：
48
作者：
Cloonan, Nicole;Forrest, Alistair R. R.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.