Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y

被引:165
作者
Nicolaides, K. H. [1 ,2 ]
Syngelaki, A. [1 ]
Gil, M. [1 ]
Atanasova, V. [1 ]
Markova, D. [1 ]
机构
[1] Kings Coll Hosp London, Harris Birthright Res Ctr Fetal Med, London, England
[2] Univ Coll London Hosp, Dept Fetal Med, London, England
关键词
MATERNAL PLASMA; FETAL DNA; TRISOMY-21; DIAGNOSIS; IMPACT; RISK;
D O I
10.1002/pd.4103
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Objective To assess the performance of cell-free DNA (cfDNA) testing in maternal blood for detection of fetal aneuploidy of chromosomes 13, 18, 21, X, and Y using targeted sequencing of single-nucleotide polymorphisms. Methods Prospective study in 242 singleton pregnancies undergoing chorionic villus sampling at 11 to 13weeks. Maternal blood was collected before chorionic villus sampling and sent to Natera (San Carlos, CA, USA). cfDNA was isolated from maternal plasma, and targeted multiplex PCR amplification followed by sequencing of 19488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y was performed. Sequencing data were analyzed using the NATUS algorithm that determines the copy number and calculates a sample-specific accuracy for each of the five chromosomes tested. Laboratory personnel were blinded to fetal karyotype. Results Results were provided for 229 (94.6%) of the 242 cases. Thirty-two cases were correctly identified as aneuploid, including trisomy 21 [n=25; sensitivity=100% (CI: 86.3100%), specificity=100% (CI: 98.2100%)], trisomy 18 (n=3), trisomy 13 (n=1), Turner syndrome (n=2), and triploidy (n=1), with no false positive or false negative results. Median accuracy was 99.9% (range: 96.0100%). Conclusions cfDNA testing in maternal blood using targeted sequencing of polymorphic loci at chromosomes 13, 18, 21, X, and Y holds promise for accurate detection of fetal autosomal trisomies, sex chromosome aneuploidies, and triploidy. (c) 2013 John Wiley & Sons, Ltd.
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收藏
页码:575 / 579
页数:5
相关论文
共 25 条
[1]   Trisomy 13 detection in the first trimester of pregnancy using a chromosome-selective cell-free DNA analysis method [J].
Ashoor, G. ;
Syngelaki, A. ;
Wang, E. ;
Struble, C. ;
Oliphant, A. ;
Song, K. ;
Nicolaides, K. H. .
ULTRASOUND IN OBSTETRICS & GYNECOLOGY, 2013, 41 (01) :21-25
[2]   Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18 [J].
Ashoor, Ghalia ;
Syngelaki, Argyro ;
Wagner, Marion ;
Birdir, Cahit ;
Nicolaides, Kypros H. .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2012, 206 (04) :322.e1-322.e5
[3]   Fetal Fraction in Maternal Plasma Cell-Free DNA at 11-13 Weeks' Gestation: Effect of Maternal and Fetal Factors [J].
Ashoor, Ghalia ;
Poon, Leona ;
Syngelaki, Argyro ;
Mosimann, Beatrice ;
Nicolaides, Kypros H. .
FETAL DIAGNOSIS AND THERAPY, 2012, 31 (04) :237-243
[4]   Genome-Wide Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing [J].
Bianchi, Diana W. ;
Platt, Lawrence D. ;
Goldberg, James D. ;
Abuhamad, Alfred Z. ;
Sehnert, Amy J. ;
Rava, Richard P. .
OBSTETRICS AND GYNECOLOGY, 2012, 119 (05) :890-901
[5]   Noninvasive Prenatal Diagnosis of Fetal Trisomy 18 and Trisomy 13 by Maternal Plasma DNA Sequencing [J].
Chen, Eric Z. ;
Chiu, Rossa W. K. ;
Sun, Hao ;
Akolekar, Ranjit ;
Chan, K. C. Allen ;
Leung, Tak Y. ;
Jiang, Peiyong ;
Zheng, Yama W. L. ;
Lun, Fiona M. F. ;
Chan, Lisa Y. S. ;
Jin, Yongjie ;
Go, Attie T. J. I. ;
Lau, Elizabeth T. ;
To, William W. K. ;
Leung, Wing C. ;
Tang, Rebecca Y. K. ;
Au-Yeung, Sidney K. C. ;
Lam, Helena ;
Kung, Yu Y. ;
Zhang, Xiuqing ;
van Vugt, John M. G. ;
Minekawa, Ryoko ;
Tang, Mary H. Y. ;
Wang, Jun ;
Oudejans, Cees B. M. ;
Lau, Tze K. ;
Nicolaides, Kypros H. ;
Lo, Y. M. Dennis .
PLOS ONE, 2011, 6 (07)
[6]   Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study [J].
Chiu, Rossa W. K. ;
Akolekar, Ranjit ;
Zheng, Yama W. L. ;
Leung, Tak Y. ;
Sun, Hao ;
Chan, K. C. Allen ;
Lun, Fiona M. F. ;
Go, Attie T. J. I. ;
Lau, Elizabeth T. ;
To, William W. K. ;
Leung, Wing C. ;
Tang, Rebecca Y. K. ;
Au-Yeung, Sidney K. C. ;
Lam, Helena ;
Kung, Yu Y. ;
Zhang, Xiuqing ;
van Vugt, John M. G. ;
Minekawa, Ryoko ;
Tang, Mary H. Y. ;
Wang, Jun ;
Oudejans, Cees B. M. ;
Lau, Tze K. ;
Nicolaides, Kypros H. ;
Lo, Y. M. Dennis .
BMJ-BRITISH MEDICAL JOURNAL, 2011, 342 :217
[7]   Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma [J].
Chiu, Rossa W. K. ;
Chan, K. C. Allen ;
Gao, Yuan ;
Lau, Virginia Y. M. ;
Zheng, Wenli ;
Leung, Tak Y. ;
Foo, Chris H. F. ;
Xie, Bin ;
Tsui, Nancy B. Y. ;
Lun, Fiona M. F. ;
Zee, Benny C. Y. ;
Lau, Tze K. ;
Cantor, Charles R. ;
Lo, Y. M. Dennis .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (51) :20458-20463
[8]   Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting [J].
Ehrich, Mathias ;
Deciu, Cosmin ;
Zwiefelhofer, Tricia ;
Tynan, John A. ;
Cagasan, Lesley ;
Tim, Roger ;
Lu, Vivian ;
McCullough, Ron ;
McCarthy, Erin ;
Nygren, Anders O. H. ;
Dean, Jarrod ;
Tang, Lin ;
Hutchison, Don ;
Lu, Tim ;
Wang, Huiquan ;
Angkachatchai, Vach ;
Oeth, Paul ;
Cantor, Charles R. ;
Bombard, Allan ;
van den Boom, Dirk .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2011, 204 (03)
[9]   Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood [J].
Fan, H. Christina ;
Blumenfeld, Yair J. ;
Chitkara, Usha ;
Hudgins, Louanne ;
Quake, Stephen R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (42) :16266-16271
[10]   First-trimester screening for trisomy 21 by free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A: impact of maternal and pregnancy characteristics [J].
Kagan, K. O. ;
Wright, D. ;
Spencer, K. ;
Molina, F. S. ;
Nicolaides, K. H. .
ULTRASOUND IN OBSTETRICS & GYNECOLOGY, 2008, 31 (05) :493-502