title: Microarray-Based Analysis of Methylation Status of CpGs in Placental DNA and Maternal Blood DNA--Potential New Epigenetic Biomarkers for Cell Free Fetal DNA-Based Diagnosis.
abstract: Epigenetic markers for cell free fetal DNA in the maternal blood circulation are highly interesting in the field of non-invasive prenatal testing since such markers will offer a possibility to quantify the amount of fetal DNA derived from different chromosomes in a maternal blood sample. The aim of the present study was to define new fetal specific epigenetic markers present in placental DNA that can be utilized in non-invasive prenatal diagnosis. We have conducted a high-resolution methylation specific beadchip microarray study assessing more than 450.000 CpG sites. We have analyzed the DNA methylation profiles of 10 maternal blood samples and compared them to 12 1st trimesters chorionic samples from normal placentas, identifying a number of CpG sites that are differentially methylated in maternal blood cells compared to chorionic tissue. To strengthen the utility of these differentially methylated CpG sites to be used with methyl-sensitive restriction enzymes (MSRE) in PCR-based NIPD, we furthermore refined the list of selected sites, containing a restriction sites for one of 16 different methylation-sensitive restriction enzymes. We present a list of markers on chromosomes 13, 18 and 21 with a potential for aneuploidy testing as well as a list of markers for regions harboring sub-microscopic deletion- or duplication syndromes.
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, 7100, Vejle, Denmark; Department of Gynecology and Obstetrics, Horsens Hospital, 8700, Horsens, Denmark; Institute of Regional Health 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, 7100, Vejle, Denmark.
authors.forename: Mads M
authors.initials: MM
authors.lastname: Aagaard
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, 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: Cathrine
authors.initials: C
authors.lastname: Bach
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, 7100, Vejle, Denmark; Institute of Regional Health 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, 7100, Vejle, Denmark; Institute of Regional Health research, University of Southern Denmark, 5000, Odense, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Bojesen
mesh_terms: D002474:Cell-Free System; D018899:CpG Islands; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First
chemical_list: D004247:DNA