IMPRINTED GENES IN NORMAL AND ABNORMAL PLACENTAL/FETAL FUNCTION

描述(申请人提供)：胎儿宫内发育迟缓(IUGR)是导致婴儿死亡和发病的重要原因，影响超过8%的妊娠。与LUGR相关的并发症包括宫内死亡、分娩中胎儿窘迫和围产期窒息。这还不包括产前困难和成年人对冠心病、高血压和糖尿病等疾病的易感性增加。虽然IUGR的原因多种多样，但在相当大比例的病例中，它与胎盘有关！功能障碍。胎盘是一个复杂的器官，除了作为一个活跃的内分泌器官外，还具有许多功能，包括营养和废物转移。印记基因在胎盘、胎儿和神经发育中起着重要作用。在目前已知的超过75个印记基因中，有21个与胎盘特有的印记模式或胎盘功能异常表达有关，表明它们在胎盘功能中发挥关键作用。为了阐明印记基因在IUGR中的作用，我们建议对已知的印记基因在正常和IUGR胎盘中的表达进行详细的分析。此外，我们还开发了一个模型，用于识别与胎盘运输功能相关的新印记基因。这些新基因的表达也将在正常和IUGR胎盘中进行研究。我们建议比较单亲和双亲组织以及IUGR和正常胎盘的基因表达谱。产生的信息将被汇编，并选择候选基因进行进一步分析。将对IUGR和正常妊娠的胎盘进行基因表达水平和SNPs关联分析。

DESCRIPTION (provided by applicant): Intrauterine growth retardation (IUGR) is a significant cause of infant mortality and morbidity, affecting over 8% of all pregnancies. lUGR-related complications include intrauterine death, intrapartum fetal distress, and perinatal asphyxia. This is in addition to both prenatal difficulties and increased adult predisposition to ailments such as coronary heart diseases, hypertension and diabetes. While the causes of IUGR are varied, in a significant proportion of cases it is associated with placenta! dysfunction. The placenta is a complex organ that performs many functions including nutrient and waste transfer, in addition to serving as an active endocrine organ. Imprinted genes play a major role in placental, fetal and neural development. Of the over 75 imprinted genes presently known, 21 are implicated in either placental-specific imprinting patterns or disruption of placental function when expressed abnormally, indicating their critical role in placental function. In order to elucidate the role of imprinted genes in IUGR we propose to undertake a detailed analysis of known imprinted gene expression in normal and IUGR placentas. In addition, we have developed a model for identifying novel imprinted genes involved in placental transport functions. The expression of these novel genes will also be studied in normal and IUGR placentas. We propose to compare gene expression profiles of uni- and bi-parental tissues, and IUGR and normal placentas. The information generated will be compiled, and candidate genes selected for further analysis. Gene expression level and SNPs association analysis will be carried out in placentas from IUGR and normal pregnancies.