Biological significance of genomic Imprinting

基因组印迹在哺乳动物的发育、生长和行为中起着至关重要的作用。父本和母本基因组之间的功能差异被认为是由于两种印记基因，即父本表达基因(Peg)和母本表达基因(Meg)。我们使用一种新的消减杂交方法系统地分离了新的peg和meg。通过减去正常受精胚胎和只有母体基因组的孤雌胚胎之间的差异来筛选PEG，通过减去正常胚胎和只有父系基因组的雄核胚胎之间的差异来筛选Megs。到目前为止，已经获得了13个印记基因，其中包括9个新基因。对这些印记基因的定位表明，它们都位于遗传学研究预测的小鼠先前预测的印记区域，这表明包括一些人类遗传病在内的各种印记效应是由于印记基因、PEGS和Megs的缺乏和/或过度生产造成的。对这些基因表达部位的系统分析表明，目前研究的所有印记基因都在胎盘组织中普遍表达，包括卵黄囊组织。我们提出了一个新的胎盘假说，即基因组印记是基因表达的机制，使一组印记基因在胎盘组织中得以表达。因此，这种机制在目前哺乳动物的发育中起着重要的作用，也可能是哺乳动物群体从祖先动物进化而来的关键。

Genomic imprinting plays an essential role on mammalian development, growth and behavior. Functional difference between paternal and maternal genomes are thought to be attributable to two kinds of imprinted genes, Peg (paternally expressed genes) and Meg (maternally expressed genes).We have isolated novel Pegs and Megs systematically using a newly developed subtraction-hybridization method. Pegs have been screened by subtraction between normal fertilized embryos and parthenogenetic embryos that have only maternal genomes and Megs by subtraction between normal embryos and androgenetic embryos that have only paternal genomes. So far 13 imprinted genes including 9 novel ones have been obtained. Mapping of these imprinted genes demonstrated that they all located in the previously estimated imprinted regions in the mouse predicted by genetical study, indicating that varieties of imprinting effects including some human genetic diseases were caused by lack and/or overproduction of the imprinted genes, Pegs and Megs.Systematic analysis on expression sites of these genes revealed that all imprinted genes so far examined were commonly expressed in placental tissues including yolk sac tissues. We proposed a novel placenta hypothesis that genomic imprinting is the mechanism of gene expression that enabled a group of the imprinted genes to be expressed in the placental tissues. Thus, this mechanise plays an important role for mammalian development at present and also might be essential for evolution of mammalian group from, ancestor animals.