Successful Computational Prediction of Novel Imprinted Genes from Epigenomic Features
Successful Computational Prediction of Novel Imprinted Genes from Epigenomic Features
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DOI：
10.1128/mcb.01355-09
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发表时间：
2010-07-01
影响因子：
5.3
通讯作者：
Soloway, Paul D.
中科院分区：
文献类型：
--
作者：
Brideau, Chelsea M.;Eilertson, Kirsten E.;Soloway, Paul D.
大约 100 个小鼠基因经历基因组印记，两个亲代等位基因之一被表观遗传沉默。印记基因影响发育、X染色体失活、肥胖、精神分裂症和糖尿病等过程，促进所有印记基因座的识别。局部序列特征已被用来预测候选印记基因，但使用互交的严格测试仅验证了三个，其中之一位于先前识别的印记簇中。在这里，我们展示了小鼠细胞中特定的表观遗传特征与小鼠的印记状态相关，并且我们鉴定了数百个预计将在小鼠中印记的基因。我们使用多层方法来验证印记表达，包括使用定制的单核苷酸多态性阵列和传统的分子方法。在对 65 个候选基因进行等位基因特异性表达的分子测定中，我们发现了 10 个在胎盘中母体表达的新印记基因。
Approximately 100 mouse genes undergo genomic imprinting, whereby one of the two parental alleles is epigenetically silenced. Imprinted genes influence processes including development, X chromosome inactivation, obesity, schizophrenia, and diabetes, motivating the identification of all imprinted loci. Local sequence features have been used to predict candidate imprinted genes, but rigorous testing using reciprocal crosses validated only three, one of which resided in previously identified imprinting clusters. Here we show that specific epigenetic features in mouse cells correlate with imprinting status in mice, and we identify hundreds of additional genes predicted to be imprinted in the mouse. We used a multitiered approach to validate imprinted expression, including use of a custom single nucleotide polymorphism array and traditional molecular methods. Of 65 candidates subjected to molecular assays for allele-specific expression, we found 10 novel imprinted genes that were maternally expressed in the placenta.