Department of Molecular Biology and Genetics, Cornell Center for Comparative and Population Genomics, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY 14853, USA.
Genetics. 2011 Sep;189(1):109-22. doi: 10.1534/genetics.111.130088. Epub 2011 Jul 29.
Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on embryonic day 17.5 (E17.5) mouse placenta cDNA samples from reciprocal cross F1 progeny of AKR and PWD mouse strains and quantified the allele-specific expression and the degree of parent-of-origin allelic imbalance. We confirmed the imprinting status of 23 known imprinted genes in the placenta and found that 12 genes reported previously to be imprinted in other tissues are also imprinted in mouse placenta. Through a well-replicated design using an orthogonal allelic-expression technology, we verified 5 novel imprinted genes that were not previously known to be imprinted in mouse (Pde10, Phf17, Phactr2, Zfp64, and Htra3). Our data suggest that most of the strongly imprinted genes have already been identified, at least in the placenta, and that evidence supports perhaps 100 additional weakly imprinted genes. Despite previous appearance that the placenta tends to display an excess of maternally expressed imprinted genes, with the addition of our validated set of placenta-imprinted genes, this maternal bias has disappeared.
许多关于基因组印记的调控、功能特化、计算预测和进化的问题,如果能有一个详尽的、能显示出亲本来源差异表达的全基因组印记基因目录,将会得到更好的解决。作为对新印记基因的初步扫描,我们在 AKR 和 PWD 两种小鼠品系的 F1 杂交后代的胚胎第 17.5 天(E17.5)胎盘 cDNA 样本上进行了 mRNA-seq 实验,并对等位基因特异性表达和亲本来源等位基因失衡的程度进行了定量分析。我们确认了胎盘 23 个已知印记基因的印记状态,并发现了 12 个之前在其他组织中报道为印记的基因在胎盘也是印记的。通过使用正交等位基因表达技术的复制良好的设计,我们验证了 5 个之前在小鼠中未被报道为印记的新印记基因(Pde10、Phf17、Phactr2、Zfp64 和 Htra3)。我们的数据表明,大多数强印记基因已经被识别,至少在胎盘是这样,并且有证据支持大约 100 个额外的弱印记基因。尽管之前的研究表明胎盘倾向于显示出过多的母源表达的印记基因,但在加入我们验证的胎盘印记基因集合后,这种母源偏倚已经消失。