先天性小耳畸形全基因组甲基化谱的建立.docVIP

  先天性小耳畸形全基因组甲基化谱的建立# 林琳，宋宇鹏，潘博，蒋海越，韩娟* （中国医学科学院整形外科医院，北京 100144） 5 10 摘要：目的 筛查先天性小耳畸形患者整个基因组存在甲基化水平异常的 CpG 岛和 CpG 位点 及其相关差异基因，进而探讨基因甲基化水平的异常与先天性小耳畸形发病之间的关系。方 法 收集我院先天性小耳畸形患者术中废弃的残耳软骨组织为研究对象（实验组）3 例，非 耳畸形（耳外伤）患者的正常耳软骨组织 3 例(对照组)。应用 Nimblegen CpG 启动子芯片， 对两组样本的基因组 DNA 进行全基因组 28226 个 CpG 岛扫描，筛选存在 CpG 岛甲基化水平差 异的基因。结果 实验组与对照组在全基因组范围内存在 36 个具有甲基化水平差异的 CpG 岛，其中有 29 个与已命名的 29 个基因相关。结论 初步建立了先天性小耳畸形甲基化谱， 发现的 36 个具有甲基化水平差异的 CpG 岛(包括其中已命名的 29 个基因)可能与先天性小耳 畸形发病相关，有待进一步实验验证。 关键词：小耳畸形；DNA 甲基化；CpG 岛 15 Establishment of DNA Methylation Profile in Congenital Microtia Lin Lin, SONG Yupeng, PAN bo, JIANG Haiyue, HAN Juan (Plastic Surgery Hospital,PUMC, Beijing 100144) 20 25 30 35 40 Abstract: Objective Screening for abnormal methylation in CpG islands and CpG sites through whole genome of congenital microtia to identify their associated genes. To discuss the relationship between abnormal methylation level of genes and the etiology of congenital microtia. Methods To collect the residual ear cartilage of 3 patients with microtia as the research object; normal ear cartilage of 3 patients without ear malformations as control. Choosing Nimblegen CpG promoter array to screen the 28226 CpG islands in the whole genome of both experimental group and control group, the genes with differential methylated CpG islands were selected. Results There were thirty-six CpG islands with differential methylated level in whole genome between experimental group and control group, in which twenty-nine CpG islands were connected with twenty-nine named genes. Conclusions The DNA methylation profile of the entire genome was initially established. The 36 abnormal methylated CpG islands, including twenty-nine named genes might, relate to the pathogenesis of the disease. Keywords: Microtia; DNA methylation; CpG island 0 引言 先天性小耳畸形是我国重要体表缺陷之一，国外报道的发生率为 0.76/万~ 4.34 /万，我 国为 5.18/万[1]。先天性小耳畸形是由于胚胎时期第 1 鳃沟及其邻近的第 1、2 鳃弓的发育异 常引起的一组颌面畸形，临床上常表现为耳廓畸形、外耳道闭锁和中耳畸形。小耳畸形病因 尚不明确，在以往遗传因素、环境因素研究基础上，以环境因素与细胞遗传物质交互作用的 表观遗传学研究为