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Article: Systematic identification of placental epigenetic signatures for the noninvasive prenatal detection of Edwards Syndrome

TitleSystematic identification of placental epigenetic signatures for the noninvasive prenatal detection of Edwards Syndrome
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2010, v. 5 n. 11 How to Cite?
AbstractBackground: Noninvasive prenatal diagnosis of fetal aneuploidy by maternal plasma analysis is challenging owing to the low fractional and absolute concentrations of fetal DNA in maternal plasma. Previously, we demonstrated for the first time that fetal DNA in maternal plasma could be specifically targeted by epigenetic (DNA methylation) signatures in the placenta. By comparing one such methylated fetal epigenetic marker located on chromosome 21 with another fetal genetic marker located on a reference chromosome in maternal plasma, we could infer the relative dosage of fetal chromosome 21 and noninvasively detect fetal trisomy 21. Here we apply this epigenetic-genetic (EGG) chromosome dosage approach to detect Edwards syndrome (trisomy 18) in the fetus noninvasively. Principal Findings: We have systematically identified methylated fetal epigenetic markers on chromosome 18 by methylated DNA immunoprecipitation (MeDIP) and tiling array analysis with confirmation using quantitative DNA methylation assays. Methylated DNA sequences from an intergenic region between the VAPA and APCDD1 genes (the VAPAAPCDD1 DNA) were detected in pre-delivery, but not post-delivery, maternal plasma samples. The concentrations correlated positively with those of an established fetal genetic marker, ZFY, in pre-delivery maternal plasma. The ratios of methylated VAPA-APCDD1(chr18) to ZFY(chrY) were higher in maternal plasma samples of 9 male trisomy 18 fetuses than those of 27 male euploid fetuses (Mann-Whitney test, P = 0.029). We defined the cutoff value for detecting trisomy 18 fetuses as mean+1.96 SD of the EGG ratios of the euploid cases. Eight of 9 trisomy 18 and 1 of 27 euploid cases showed EGG ratios higher than the cutoff value, giving a sensitivity of 88.9% and a specificity of 96.3%. Conclusions: Our data have shown that the methylated VAPA-APCDD1 DNA in maternal plasma is redominantly derived from the fetus. We have demonstrated that this novel fetal epigenetic marker in maternal plasma is useful for the noninvasive detection of fetal trisomy 18. © Tsui et al.
Persistent Identifierhttp://hdl.handle.net/10722/180699
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTsui, DWYen_US
dc.contributor.authorLam, YMDen_US
dc.contributor.authorLee, WSen_US
dc.contributor.authorLeung, TYen_US
dc.contributor.authorLau, TKen_US
dc.contributor.authorLau, ETen_US
dc.contributor.authorTang, MHYen_US
dc.contributor.authorAkolekar, Ren_US
dc.contributor.authorNicolaides, KHen_US
dc.contributor.authorChiu, RWKen_US
dc.contributor.authorDennis Lo, YMen_US
dc.contributor.authorChim, SSCen_US
dc.date.accessioned2013-01-28T01:41:13Z-
dc.date.available2013-01-28T01:41:13Z-
dc.date.issued2010en_US
dc.identifier.citationPlos One, 2010, v. 5 n. 11en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10722/180699-
dc.description.abstractBackground: Noninvasive prenatal diagnosis of fetal aneuploidy by maternal plasma analysis is challenging owing to the low fractional and absolute concentrations of fetal DNA in maternal plasma. Previously, we demonstrated for the first time that fetal DNA in maternal plasma could be specifically targeted by epigenetic (DNA methylation) signatures in the placenta. By comparing one such methylated fetal epigenetic marker located on chromosome 21 with another fetal genetic marker located on a reference chromosome in maternal plasma, we could infer the relative dosage of fetal chromosome 21 and noninvasively detect fetal trisomy 21. Here we apply this epigenetic-genetic (EGG) chromosome dosage approach to detect Edwards syndrome (trisomy 18) in the fetus noninvasively. Principal Findings: We have systematically identified methylated fetal epigenetic markers on chromosome 18 by methylated DNA immunoprecipitation (MeDIP) and tiling array analysis with confirmation using quantitative DNA methylation assays. Methylated DNA sequences from an intergenic region between the VAPA and APCDD1 genes (the VAPAAPCDD1 DNA) were detected in pre-delivery, but not post-delivery, maternal plasma samples. The concentrations correlated positively with those of an established fetal genetic marker, ZFY, in pre-delivery maternal plasma. The ratios of methylated VAPA-APCDD1(chr18) to ZFY(chrY) were higher in maternal plasma samples of 9 male trisomy 18 fetuses than those of 27 male euploid fetuses (Mann-Whitney test, P = 0.029). We defined the cutoff value for detecting trisomy 18 fetuses as mean+1.96 SD of the EGG ratios of the euploid cases. Eight of 9 trisomy 18 and 1 of 27 euploid cases showed EGG ratios higher than the cutoff value, giving a sensitivity of 88.9% and a specificity of 96.3%. Conclusions: Our data have shown that the methylated VAPA-APCDD1 DNA in maternal plasma is redominantly derived from the fetus. We have demonstrated that this novel fetal epigenetic marker in maternal plasma is useful for the noninvasive detection of fetal trisomy 18. © Tsui et al.en_US
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_US
dc.relation.ispartofPLoS ONEen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleSystematic identification of placental epigenetic signatures for the noninvasive prenatal detection of Edwards Syndromeen_US
dc.typeArticleen_US
dc.identifier.emailTang, MHY: mhytang@hkucc.hku.hken_US
dc.identifier.authorityTang, MHY=rp01701en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0015069en_US
dc.identifier.pmid21152411-
dc.identifier.scopuseid_2-s2.0-78649773775en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78649773775&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume5en_US
dc.identifier.issue11en_US
dc.identifier.isiWOS:000284755100058-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridTsui, DWY=23096203700en_US
dc.identifier.scopusauthoridLam, YMD=36997974200en_US
dc.identifier.scopusauthoridLee, WS=7407084160en_US
dc.identifier.scopusauthoridLeung, TY=7202110959en_US
dc.identifier.scopusauthoridLau, TK=24491963900en_US
dc.identifier.scopusauthoridLau, ET=36006491400en_US
dc.identifier.scopusauthoridTang, MHY=8943401300en_US
dc.identifier.scopusauthoridAkolekar, R=25724167500en_US
dc.identifier.scopusauthoridNicolaides, KH=7203078780en_US
dc.identifier.scopusauthoridChiu, RWK=7103038413en_US
dc.identifier.scopusauthoridDennis Lo, YM=7401935391en_US
dc.identifier.scopusauthoridChim, SSC=6701728226en_US

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