母儿差异DNA甲基化片段用于唐氏综合征诊断的初步探索

Preliminary research on prenatal diagnosis of Down’s syndrome using different methylated DNA fragments between fetus and mother

目的对文献已有报道的胎盘和白细胞之间甲基化水平有差异的DNA片段在大样本中国人群进行验证,探索可能用于中国人群的DNA甲基化标记物。方法以母亲胎盘胎儿面和外周血白细胞为研究对象,采用甲基化敏感性限制性内切酶酶切,检测母亲外周血白细胞和母亲胎盘胎儿面甲基化状态的差别,并在孕妇外周血血浆中进行检测,寻找可能的标记。结果通过甲基化敏感性酶切分析的方法,已报道的标记物中,无一能作为临床可用的非侵入性产前诊断唐氏综合征的胎儿DNA甲基化标记。结论通过Hpa Ⅱ-MspⅠ酶切法分析区分母儿DNA的方法需要进一步探索。已报道的标记物中,无一能作为临床可用的非侵入性产前诊断唐氏综合征的胎儿DNA甲基化标记。

Objective To identify different methylated DNA fragments reported by literature between the placenta and leukocyte in a large group of Chinese people and explore the potential applicable DNA markers. Methods Samples include placenta of fetal origin and maternal peripheral leukocyte.We adopted the strategy of methylation-specific enzyme digestion assay to detect these DNA sequences between the two,we also identified these sequences in maternal plasma in order to search for clinical applicable markers.Results None of the reported epigenetic fetal DNA biomarkers can be used for non-invasive prenatal diagnosis on Down syndrome by the methylation-specific enzyme analysis in Chinese population.Conclusion To differentiate fetal DNA from maternal DNA using Hpa Ⅱ-Msp Ⅰanalysis needs further consideration. And more efforts have to be made for the prenatal diagnosis of Down syndrome using epigenetic biomarkers different methylated between fetus and mother.None of the reported epigenetic fetal DNA biomarkers is applicable for the clinical non-invasive prenatal diagnosis of Down syndrome.