Clinical Chemistry
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Clinical Chemistry 54: 500-511, 2008. First published January 17, 2008; 10.1373/clinchem.2007.098731
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
clinchem.2007.098731v1
54/3/500    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (14)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chim, S. S.C.
Right arrow Articles by Lo, Y.M. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chim, S. S.C.
Right arrow Articles by Lo, Y.M. D.
Related Collections
Right arrow Molecular Diagnostics and Genetics
(Clinical Chemistry. 2008;54:500-511.)
© 2008 American Association for Clinical Chemistry, Inc.


Molecular Diagnostics and Genetics

Systematic Search for Placental DNA-Methylation Markers on Chromosome 21: Toward a Maternal Plasma-Based Epigenetic Test for Fetal Trisomy 21

Stephen S.C. Chim1,2, Shengnan Jin1,3, Tracy Y.H. Lee1,3, Fiona M.F. Lun1,3, Wing S. Lee1,3, Lisa Y.S. Chan1,3, Yongjie Jin1,4, Ningning Yang1,3, Yu K. Tong1,3, Tak Y. Leung2, Tze K. Lau1,2, Chunming Ding1,4, Rossa W.K. Chiu1,3 and Y.M. Dennis Lo1,3,a

1 Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences; 2 Department of Obstetrics and Gynaecology; 3 Department of Chemical Pathology; 4 Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.

aAddress correspondence to this author at: Department of Chemical Pathology, Rm. 38061, 1/F, Clinical Sciences Building, Prince of Wales Hospital, 30-32 Ngan Shing St., Shatin, Hong Kong SAR. Fax 852-2636-5090; e-mail loym{at}cuhk.edu.hk.

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.

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)—76% of the 149 CGIs on chromosome 21 identified by bioinformatic criteria—for differentially methylated DNA patterns. The methylation index (MI) of a CpG site was estimated as the proportion of molecules methylated at that site.

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, 0.22–0.65), or completely methylated (MI = 1.00) in maternal blood cells and hypomethylated in the placenta (MI range, 0.00–0.75). We detected, for the first time, placental DNA-methylation patterns on chromosome 21 in maternal plasma during pregnancy and observed their postpartum clearance.

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.




The following articles in journals at HighWire Press have cited this article:


Home page
BioinformaticsHome page
T. Chu, K. Bunce, W. A. Hogge, and D. G. Peters
Statistical model for whole genome sequencing and its application to minimally invasive diagnosis of fetal genetic disease
Bioinformatics, May 15, 2009; 25(10): 1244 - 1250.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
E. A. Papageorgiou, H. Fiegler, V. Rakyan, S. Beck, M. Hulten, K. Lamnissou, N. P. Carter, and P. C. Patsalis
Sites of Differential DNA Methylation between Placenta and Peripheral Blood: Molecular Markers for Noninvasive Prenatal Diagnosis of Aneuploidies
Am. J. Pathol., May 1, 2009; 174(5): 1609 - 1618.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Pathol.Home page
E C W Hung, R W K Chiu, and Y M D Lo
Detection of circulating fetal nucleic acids: a review of methods and applications
J. Clin. Pathol., April 1, 2009; 62(4): 308 - 313.
[Abstract] [Full Text] [PDF]


Home page
Clin. Chem.Home page
J. Beck, H. B. Urnovitz, J. Riggert, M. Clerici, and E. Schutz
Profile of the Circulating DNA in Apparently Healthy Individuals
Clin. Chem., April 1, 2009; 55(4): 730 - 738.
[Abstract] [Full Text] [PDF]


Home page
Hum Reprod UpdateHome page
C. F. Wright and H. Burton
The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis
Hum. Reprod. Update, January 1, 2009; 15(1): 139 - 151.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
R. W. K. Chiu, K. C. A. Chan, Y. Gao, V. Y. M. Lau, W. Zheng, T. Y. Leung, C. H. F. Foo, B. Xie, N. B. Y. Tsui, F. M. F. Lun, et al.
Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma
PNAS, December 23, 2008; 105(51): 20458 - 20463.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
F. M. F. Lun, N. B. Y. Tsui, K. C. A. Chan, T. Y. Leung, T. K. Lau, P. Charoenkwan, K. C. K. Chow, W. Y. W. Lo, C. Wanapirak, T. Sanguansermsri, et al.
Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma
PNAS, December 16, 2008; 105(50): 19920 - 19925.
[Abstract] [Full Text] [PDF]


Home page
NeoReviewsHome page
J. F. Smith and Y. Blumenfeld
Cell-free Fetal DNA in Maternal Plasma: Progress and Potential
NeoReviews, August 1, 2008; 9(8): e332 - e337.
[Abstract] [Full Text] [PDF]


Home page
Clin. Chem.Home page
C. B. M. Oudejans
Noncoding RNA and DNA as Biomarkers: Toward an Epigenetic Fetal Barcode for Use in Maternal Plasma
Clin. Chem., March 1, 2008; 54(3): 456 - 457.
[Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the American Association for Clinical Chemistry.