评估出生缺陷风险的父源性表观遗传学标志物--相关印记基因筛选

项目名称： 评估出生缺陷风险的父源性表观遗传学标志物--相关印记基因筛选

项目编号： No.81673185

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 强梅

作者单位： 山西医科大学

项目金额： 25万元

中文摘要： 出生缺陷已成为影响我国人口生育健康的重大社会问题。其病因机制尚未阐明, 建立有效的筛查系统是预防出生缺陷的一个重要挑战。表观遗传学研究为疾病的病因探索和防治策略提供新的思路。印记基因甲基化是一个独特的表观遗传学调节方式，在胎盘功能和胎儿的发育中有特定的作用。新近研究指出，父源性暴露于环境污染物诱导印记基因甲基化异常。鉴于印记基因甲基化对环境致畸物极其敏感，我们的假设是：精子印记基因甲基化可能成为环境致畸因素致出生缺陷的表观遗传学标志物。本研究拟首先利用致畸物暴露的动物模型应用高通量基因甲基化测序分析技术初选出精子印记基因甲基化区敏感的候选基因；然后采用病例-对照和追踪观察的方法对上述候选印记基因进行人群的特异性验证。其结果对于探讨父源性因素通过印记基因调控胎儿发育的机制具有重要学术意义，亦为从精准医学的角度建立精子出生缺陷相关印记基因筛查系统提供理论依据和数据支持，以提升出生缺陷防控水平。

中文关键词： 出生缺陷；印记基因；表观遗传学；筛查；父源性

英文摘要： Birth defects are the major social problems impacting on reproductive health in China. Due to exact mechanisms of birth defects remain unclear; it is a challenge to establish an effective preventive screening system for birth defects. Epigenetic study has provided new insight for exploring etiology and preventive strategies. Imprinting gene methylation is a special type of epigenetic regulations, which plays an important role on placenta function and fetal development. Recent studies indicated that paternally exposed to environmental pollutants induced the changes of imprinting gene methylation. In view of the methylation regions (DMRs) of imprinted genes is extremely sensitive to environmental teratogens, we hypothesizes that sperm imprinting gene methylation may become an epigenetic biomarker for birth defects in responding to environmental teratogens. To address this proposal aim, we will first screen the candidate imprinting gene sensitive to environmental teratogens in DMRs in the mice exposure model by using next generation sequencing; then we will verify the specificity of these candidate genes through human epidemiological studies of case-control and follow-up studies. The results from the proposed study will be of important in exploring the molecular mechanisms underlying the contribution of paternal factors to the control of fetal development. Also, this proposed study will provide the base in theory and actually data base for establishment of the sperm birth defects relevant imprinting gene screening system.

英文关键词： Birth defects;Imprinting genes;Epigenetics ;Screening;Paternal