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Article: Differential DNA methylation between fetus and mother as a strategy for detecting fetal DNA in maternal plasma

TitleDifferential DNA methylation between fetus and mother as a strategy for detecting fetal DNA in maternal plasma
Authors
Issue Date2002
PublisherAmerican Association for Clinical Chemistry, Inc. The Journal's web site is located at http://www.clinchem.org
Citation
Clinical Chemistry, 2002, v. 48 n. 1, p. 35-41 How to Cite?
AbstractBackground: Fetal DNA has been detected in maternal plasma by the use of genetic differences between mother and fetus. We explore the possibility of using epigenetic markers for the specific detection of fetal DNA in maternal plasma. Methods: A differentially methylated region in the human IGF2-H19 locus and a single-nucleotide polymorphism in this region were chosen for the study. The methylation status in this region is maintained in such a way that the paternal allele is methylated and the maternal allele is unmethylated. The single-nucleotide polymorphism was typed by direct sequencing of PCR products. The methylation status of this region was ascertained by bisulfite conversion and methylation-specific PCR. Differentially methylated fetal alleles were detected in maternal plasma by direct sequencing and a primer-extension assay. Results: Women in the second (n = 21; 17-21 weeks) and third (n = 18; 37-42 weeks) trimesters of pregnancy were recruited. Among these 39 volunteers, the 16 who were heterozygous for the single-nucleotide polymorphism were chosen for further analysis. In 11 of these 16 cases, paternally inherited methylated fetal alleles were different from the methylated alleles of the respective mothers. Using direct sequencing, we detected paternally inherited methylated fetal DNA in 6 of 11 (55%) cases. In 8 of the 16 heterozygous cases, the fetuses possessed an unmethylated maternally inherited allele that was different from the unmethylated allele of the mother. Using a primer-extension assay, we detected fetal-derived maternally inherited alleles in maternal plasma of four of eight (50%) cases. Conclusions: These results represent the first use of fetal epigenetic markers in noninvasive prenatal analysis. These data may also have implications for the investigation of other types of chimerism. © 2002 American Association for Clinical Chemistry.
Persistent Identifierhttp://hdl.handle.net/10722/179775
ISSN
2015 Impact Factor: 7.457
2015 SCImago Journal Rankings: 2.472
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPoon, LLMen_US
dc.contributor.authorLeung, TNen_US
dc.contributor.authorLau, TKen_US
dc.contributor.authorChow, KCKen_US
dc.contributor.authorLo, YMDen_US
dc.date.accessioned2012-12-19T10:04:30Z-
dc.date.available2012-12-19T10:04:30Z-
dc.date.issued2002en_US
dc.identifier.citationClinical Chemistry, 2002, v. 48 n. 1, p. 35-41en_US
dc.identifier.issn0009-9147en_US
dc.identifier.urihttp://hdl.handle.net/10722/179775-
dc.description.abstractBackground: Fetal DNA has been detected in maternal plasma by the use of genetic differences between mother and fetus. We explore the possibility of using epigenetic markers for the specific detection of fetal DNA in maternal plasma. Methods: A differentially methylated region in the human IGF2-H19 locus and a single-nucleotide polymorphism in this region were chosen for the study. The methylation status in this region is maintained in such a way that the paternal allele is methylated and the maternal allele is unmethylated. The single-nucleotide polymorphism was typed by direct sequencing of PCR products. The methylation status of this region was ascertained by bisulfite conversion and methylation-specific PCR. Differentially methylated fetal alleles were detected in maternal plasma by direct sequencing and a primer-extension assay. Results: Women in the second (n = 21; 17-21 weeks) and third (n = 18; 37-42 weeks) trimesters of pregnancy were recruited. Among these 39 volunteers, the 16 who were heterozygous for the single-nucleotide polymorphism were chosen for further analysis. In 11 of these 16 cases, paternally inherited methylated fetal alleles were different from the methylated alleles of the respective mothers. Using direct sequencing, we detected paternally inherited methylated fetal DNA in 6 of 11 (55%) cases. In 8 of the 16 heterozygous cases, the fetuses possessed an unmethylated maternally inherited allele that was different from the unmethylated allele of the mother. Using a primer-extension assay, we detected fetal-derived maternally inherited alleles in maternal plasma of four of eight (50%) cases. Conclusions: These results represent the first use of fetal epigenetic markers in noninvasive prenatal analysis. These data may also have implications for the investigation of other types of chimerism. © 2002 American Association for Clinical Chemistry.en_US
dc.languageengen_US
dc.publisherAmerican Association for Clinical Chemistry, Inc. The Journal's web site is located at http://www.clinchem.orgen_US
dc.relation.ispartofClinical Chemistryen_US
dc.subject.meshDna - Blood - Geneticsen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshFemaleen_US
dc.subject.meshFetus - Metabolismen_US
dc.subject.meshGenomic Imprintingen_US
dc.subject.meshHeterozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshPolymorphism, Single Nucleotideen_US
dc.subject.meshPregnancyen_US
dc.titleDifferential DNA methylation between fetus and mother as a strategy for detecting fetal DNA in maternal plasmaen_US
dc.typeArticleen_US
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_US
dc.identifier.authorityPoon, LLM=rp00484en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid11751536-
dc.identifier.scopuseid_2-s2.0-0036140193en_US
dc.identifier.hkuros108438-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036140193&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume48en_US
dc.identifier.issue1en_US
dc.identifier.spage35en_US
dc.identifier.epage41en_US
dc.identifier.isiWOS:000172936900005-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPoon, LLM=7005441747en_US
dc.identifier.scopusauthoridLeung, TN=7202110927en_US
dc.identifier.scopusauthoridLau, TK=24491963900en_US
dc.identifier.scopusauthoridChow, KCK=25951247200en_US
dc.identifier.scopusauthoridLo, YMD=7401935391en_US

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