title: Novel Epigenetic Markers on Chromosome 21 for Noninvasive Prenatal Testing of Fetal Trisomy 21.
abstract: Until now, fetal placenta-specific epigenetic markers for noninvasive prenatal testing of fetal trisomy 21 (T21) have been identified based only on differences in tissue-specific epigenetic characteristics between placenta and maternal blood, but these characteristics have not been validated in T21 placenta. We aimed to discover novel epigenetic markers on chromosome 21 that show a hypermethylated pattern in fetal placenta compared with blood, regardless of the presence of T21. We performed a high-resolution tiling array analysis of chromosome 21 using the methylated-CpG binding domain protein-based method. We identified 93 epigenetic regions that showed fetal placenta-specific differential methylation patterns; among these, three regions showed fetal placenta-specific methylation patterns in T21 placenta samples. The methylation patterns of these three regions in the array were confirmed by bisulfite direct sequencing. The three regions were detectable in first-trimester maternal plasma. Moreover, a combination of their methylation ratio achieved high diagnostic accuracy for noninvasive prenatal testing of fetal T21 by further statistical analysis. These three novel regions with fetal placenta-specific differential methylation patterns on chromosome 21 were identified irrespective of the presence of T21. Our findings suggest that epigenetic characteristics of markers according to the presence or absence of T21 should be considered in the development of noninvasive prenatal testing of fetal T21 using fetal placenta-specific epigenetic markers.
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Republic of Korea.
authors.forename: Da Eun
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Republic of Korea.
authors.forename: Ji Hyae
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Republic of Korea.
authors.forename: Min Hyoung
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Republic of Korea. Electronic address: sy5.park@cgh.co.kr.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Republic of Korea; Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Republic of Korea. Electronic address: hmryu@cgh.co.kr.
authors.forename: Hyun Mee
authors.initials: HM
authors.lastname: Ryu
mesh_terms: D002891:Chromosomes, Human, Pair 21; D016000:Cluster Analysis; D018899:CpG Islands; D056915:DNA Copy Number Variations; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics*; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D060885:Multiplex Polymerase Chain Reaction; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011296:Prenatal Diagnosis; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers