Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the Fetus

被引：812

作者：

Lo, Y. M. Dennis ^{[1
,2
]}

Chan, K. C. Allen ^{[1
,2
]}

Sun, Hao ^{[1
,2
]}

Chen, Eric Z. ^{[1
,2
]}

Jiang, Peiyong ^{[1
,2
]}

Lun, Fiona M. F. ^{[1
,2
]}

Zheng, Yama W. ^{[1
,2
]}

Leung, Tak Y. ^{[3
]}

Lau, Tze K. ^{[3
]}

Cantor, Charles R. ^{[4
]}

Chiu, Rossa W. K. ^{[1
,2
]}

机构：

[1] Chinese Univ Hong Kong, Prince Wales Hosp, Li Ka Shing Inst Hlth Sci, Ctr Res Circulating Fetal Nucle Acids, Shatin, Hong Kong, Peoples R China

[2] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Chem Pathol, Shatin, Hong Kong, Peoples R China

[3] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Obstet & Gynaecol, Shatin, Hong Kong, Peoples R China

[4] Sequenom Inc, San Diego, CA 92121 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2010年 / 2卷 / 61期

关键词：

CELL-FREE DNA; NONINVASIVE PRENATAL-DIAGNOSIS; FETAL DNA; SIZE DISTRIBUTIONS; COUNTING ALLELES; DIGITAL PCR; SELECTION;

D O I：

10.1126/scitranslmed.3001720

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cell-free fetal DNA is present in the plasma of pregnant women. It consists of short DNA fragments among primarily maternally derived DNA fragments. We sequenced a maternal plasma DNA sample at up to 65-fold genomic coverage. We showed that the entire fetal and maternal genomes were represented in maternal plasma at a constant relative proportion. Plasma DNA molecules showed a predictable fragmentation pattern reminiscent of nuclease-cleaved nucleosomes, with the fetal DNA showing a reduction in a 166-base pair (bp) peak relative to a 143-bp peak, when compared with maternal DNA. We constructed a genome-wide genetic map and determined the mutational status of the fetus from the maternal plasma DNA sequences and from information about the paternal genotype and maternal haplotype. Our study suggests the feasibility of using genome-wide scanning to diagnose fetal genetic disorders prenatally in a noninvasive way.

引用

页数：13

共 39 条

[1] Ethical challenges in providing noninvasive prenatal diagnosis [J].

Benn, Peter A. ;

Chapman, Audrey R. .

CURRENT OPINION IN OBSTETRICS & GYNECOLOGY, 2010, 22 (02) :128-134

[2] Hypermethylated RASSF1A in maternal plasma:: A universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis [J].

Chan, K. C. Allen ;

Ding, Chunming ;

Gerovassili, Ageliki ;

Yeung, Sze W. ;

Chiu, Rossa W. K. ;

Leung, Tse N. ;

Lau, Tze K. ;

Chim, Stephen S. C. ;

Chung, Grace T. Y. ;

Nicolaides, Kypros H. ;

Lo, Y. M. Dennis .

CLINICAL CHEMISTRY, 2006, 52 (12) :2211-2218

[3] Effects of preanalytical factors on the molecular size of cell-free DNA in blood [J].

Chan, KCA ;

Yeung, SW ;

Lui, WB ;

Rainer, TH ;

Lo, YMD .

CLINICAL CHEMISTRY, 2005, 51 (04) :781-784

[4] Size distributions of maternal and fetal DNA in maternal plasma [J].

Chan, KCA ;

Zhang, J ;

Hui, ABY ;

Wong, N ;

Lau, TK ;

Leung, TN ;

Lo, KW ;

Huang, DWS ;

Lo, YMD .

CLINICAL CHEMISTRY, 2004, 50 (01) :88-92

[5] Maternal Plasma DNA Analysis with Massively Parallel Sequencing by Ligation for Noninvasive Prenatal Diagnosis of Trisomy 21 [J].

Chiu, Rossa W. K. ;

Sun, Hao ;

Akolekar, Ranjit ;

Clouser, Christopher ;

Lee, Clarence ;

McKernan, Kevin ;

Zhou, Daixing ;

Nicolaides, Kypros H. ;

Lo, Y. M. Dennis .

CLINICAL CHEMISTRY, 2010, 56 (03) :459-463

[6] 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

[7] New strategy for prenatal diagnosis of X-linked disorders. [J].

Costa, JM ;

Benachi, A ;

Gautier, E .

NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (19) :1502-1502

[8] Non-invasive prenatal testing: ethical issues explored [J].

de Jong, Antina ;

Dondorp, Wybo J. ;

de Die-Smulders, Christine E. M. ;

Frints, Suzanne G. M. ;

de Wert, Guido M. W. R. .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2010, 18 (03) :272-277

[9] Direct molecular haplotyping of long-range genomic DNA with M1-PCR [J].

Ding, CM ;

Cantor, CR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (13) :7449-7453

[10] Getting more from digital SNP data [J].

El Karoui, Noureddine ;

Zhou, Wei ;

Whittemore, Alice S. .

STATISTICS IN MEDICINE, 2006, 25 (18) :3124-3133

← 1 2 3 4 →