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Biological significance of genomic Imprinting

基因组印记的生物学意义

基本信息

批准号：
08458216
负责人：
ISHINO Fumitoshi
金额：
$ 4.93万
依托单位：
TOKYO INSTITUTE OF TECHNOLOGY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

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.

基因组印记在哺乳动物的发育、生长和行为中起着重要的作用。父本和母本基因组之间的功能差异被认为是由两种印记基因Peg（父本表达基因）和Meg（母本表达基因）引起的。通过在正常受精胚胎和仅具有母本基因组的孤雌生殖胚胎之间进行减法来筛选PEG，并且通过在正常胚胎和仅具有父本基因组的雄激素发生胚胎之间进行减法来筛选Megs。目前已获得13个印迹基因，其中9个为新的印迹基因。这些印迹基因的定位结果表明，它们均位于遗传学研究预测的小鼠印迹区域内，表明包括人类遗传疾病在内的各种印迹效应都是由印迹基因的缺失和/或过量产生引起的，对这些基因表达位点的系统分析显示，迄今为止检测到的所有印迹基因通常在胎盘组织中表达，组织包括卵黄囊组织。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表达。因此，这一机制在哺乳动物的发育中起着重要的作用，也可能是哺乳动物从祖先动物进化到哺乳动物类群的必要条件。