title: Microarray-Based Analysis of Methylation of 1st Trimester Trisomic Placentas from Down Syndrome, Edwards Syndrome and Patau Syndrome.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark.|Department of Gynecology and Obstetrics, Horsens Hospital, 8700 Horsens, Denmark.|Institute of Regional Health services research, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Hatt
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark.
authors.forename: Mads M
authors.initials: MM
authors.lastname: Aagaard
authors.affiliation: Department of Gynecology and Obstetrics, Horsens Hospital, 8700 Horsens, Denmark.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Bach
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Graakjaer
authors.affiliation: Department of Gynecology and Obstetrics, Horsens Hospital, 8700 Horsens, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Sommer
authors.affiliation: Department of Gynecology and Obstetrics, Horsens Hospital, 8700 Horsens, Denmark.
authors.forename: Inge E
authors.initials: IE
authors.lastname: Agerholm
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark.|Institute of Regional Health services research, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Kølvraa
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark.|Institute of Regional Health services research, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Bojesen
mesh_terms: D025063:Chromosome Disorders / Q000378:metabolism*; D002882:Chromosomes, Human, Pair 13 / Q000378:metabolism; D002887:Chromosomes, Human, Pair 18 / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004314:Down Syndrome / Q000378:metabolism*; D005260:Female; D006801:Humans; D046228:Microarray Analysis; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D014314:Trisomy; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome