{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:05:38Z","timestamp":1790892338157,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T00:00:00Z","timestamp":1204329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100010428","name":"Innovation and Technology Fund","doi-asserted-by":"publisher","award":["ITS\/195\/01"],"award-info":[{"award-number":["ITS\/195\/01"]}],"id":[{"id":"10.13039\/501100010428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003452","name":"Innovation and Technology Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: The presence of fetal DNA in maternal plasma represents a source of fetal genetic material for noninvasive prenatal diagnosis; however, the coexisting background maternal DNA complicates the analysis of aneuploidy in such fetal DNA. Recently, the SERPINB5 gene on chromosome 18 was shown to exhibit different DNA-methylation patterns in the placenta and maternal blood cells, and the allelic ratio for placenta-derived hypomethylated SERPINB5 in maternal plasma was further shown to be useful for noninvasive detection of fetal trisomy 18.<\/jats:p>\n               <jats:p>Methods: To develop a similar method for the noninvasive detection of trisomy 21, we used methylation-sensitive single nucleotide primer extension and\/or bisulfite sequencing to systematically search 114 CpG islands (CGIs)\u201476% of the 149 CGIs on chromosome 21 identified by bioinformatic criteria\u2014for differentially methylated DNA patterns. The methylation index (MI) of a CpG site was estimated as the proportion of molecules methylated at that site.<\/jats:p>\n               <jats:p>Results: We identified 22 CGIs which were shown to contain CpG sites that were either completely unmethylated (MI = 0.00) in maternal blood cells and methylated in the placenta (MI range, 0.22\u20130.65), or completely methylated (MI = 1.00) in maternal blood cells and hypomethylated in the placenta (MI range, 0.00\u20130.75). We detected, for the first time, placental DNA-methylation patterns on chromosome 21 in maternal plasma during pregnancy and observed their postpartum clearance.<\/jats:p>\n               <jats:p>Conclusion: Twenty-two (19%) of the 114 studied CGIs on chromosome 21 showed epigenetic differences between samples of placenta and maternal blood cells; these CGIs may provide a rich source of markers for noninvasive prenatal diagnosis.<\/jats:p>","DOI":"10.1373\/clinchem.2007.098731","type":"journal-article","created":{"date-parts":[[2008,1,17]],"date-time":"2008-01-17T20:45:57Z","timestamp":1200602757000},"page":"500-511","source":"Crossref","is-referenced-by-count":113,"title":["Systematic Search for Placental DNA-Methylation Markers on Chromosome 21: Toward a Maternal Plasma-Based Epigenetic Test for Fetal Trisomy 21"],"prefix":"10.1093","volume":"54","author":[{"given":"Stephen S C","family":"Chim","sequence":"first","affiliation":[{"name":"Centre for Research into Circulating Fetal 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SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Yang","sequence":"first","affiliation":[{"name":"Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences"},{"name":"Department of Chemical Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu K","family":"Tong","sequence":"first","affiliation":[{"name":"Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences"},{"name":"Department of Chemical Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak Y","family":"Leung","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze K","family":"Lau","sequence":"first","affiliation":[{"name":"Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences"},{"name":"Department of Obstetrics and 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