Hatt Lotte, Aagaard Mads M, Bach Cathrine, Graakjaer Jesper, Sommer Steffen, Agerholm Inge E, Kølvraa Steen, Bojesen Anders
Department of Clinical Genetics, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark.
Department of Gynecology and Obstetrics, Horsens Hospital, 8700 Horsens, Denmark.
PLoS One. 2016 Aug 4;11(8):e0160319. doi: 10.1371/journal.pone.0160319. eCollection 2016.
Methylation-based non-invasive prenatal testing of fetal aneuploidies is an alternative method that could possibly improve fetal aneuploidy diagnosis, especially for trisomy 13(T13) and trisomy 18(T18). Our aim was to study the methylation landscape in placenta DNA from trisomy 13, 18 and 21 pregnancies in an attempt to find trisomy-specific methylation differences better suited for non-invasive prenatal diagnosis. We have conducted high-resolution methylation specific bead chip microarray analyses assessing more than 450,000 CpGs analyzing placentas from 12 T21 pregnancies, 12 T18 pregnancies and 6 T13 pregnancies. We have compared the methylation landscape of the trisomic placentas to the methylation landscape from normal placental DNA and to maternal blood cell DNA. Comparing trisomic placentas to normal placentas we identified 217 and 219 differentially methylated CpGs for CVS T18 and CVS T13, respectively (delta β>0.2, FDR<0.05), but only three differentially methylated CpGs for T21. However, the methylation differences was only modest (delta β<0.4), making them less suitable as diagnostic markers. Gene ontology enrichment analysis revealed that the gene set connected to theT18 differentially methylated CpGs was highly enriched for GO terms related to"DNA binding" and "transcription factor binding" coupled to the RNA polymerase II transcription. In the gene set connected to the T13 differentially methylated CpGs we found no significant enrichments.
基于甲基化的胎儿非整倍体无创产前检测是一种可能改善胎儿非整倍体诊断的替代方法，尤其是对于13三体（T13）和18三体（T18）。我们的目的是研究13三体、18三体和21三体妊娠胎盘DNA中的甲基化图谱，试图找到更适合无创产前诊断的三体特异性甲基化差异。我们进行了高分辨率甲基化特异性珠芯片微阵列分析，评估了超过45万个CpG，分析了12例21三体妊娠、12例18三体妊娠和6例13三体妊娠的胎盘。我们将三体胎盘的甲基化图谱与正常胎盘DNA和母体血细胞DNA的甲基化图谱进行了比较。将三体胎盘与正常胎盘进行比较，我们分别在绒毛取样的18三体和13三体中鉴定出217个和219个差异甲基化的CpG（δβ>0.2，FDR<0.05），但21三体中只有3个差异甲基化的CpG。然而，甲基化差异仅为中等程度（δβ<0.4），使其不太适合作为诊断标志物。基因本体富集分析显示，与1十八三体差异甲基化CpG相关的基因集高度富集与“DNA结合”和“转录因子结合”相关的GO术语，并与RNA聚合酶II转录偶联。在与13三体差异甲基化CpG相关的基因集中，我们未发现显著富集。
