title: DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.
abstract: Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia.
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Junyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Xinyao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Xu
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Xia
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China xzzhao@fudan.edu.cn.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Zhao
mesh_terms: D044466:Asian People; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002681:China; D004247:DNA / Q000097:blood / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005315:Fetal Diseases / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D055106:Genome-Wide Association Study; D006801:Humans; D047468:Immunoprecipitation; D062145:Maternal Serum Screening Tests / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D011261:Pregnancy Trimester, First
chemical_list: D015415:Biomarkers; D004247:DNA
keywords: comparative methylome analysis; fetal DNA marker; non-invasive prenatal testing