Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting

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 T.; Boom, Dirk van den

doi:10.1016/j.ajog.2010.12.060

Cited by 426 publications

(373 citation statements)

References 23 publications

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“…Between 2011 and 2013, there were at least eight widely quoted validation studies spread across four laboratories offering NIPS clinically. [4][5][6][7][8][20][21][22] Validation studies reached similar conclusions. NIPS had very high DR and SPEC, reaching nearly 99% for Down syndrome caused by trisomy 21, translocations, and trisomy 21 mosaicism.…”

Section: Acmg Statementsupporting

confidence: 59%

“…Sequencing with quantification can be random, targeted, and followed by quantification or exploitation of single-nucleotide polymorphisms. [4][5][6][7][8] Alternatively, sequencing can take place by measuring the release of hydrogen ions as nucleotides are added to a DNA template (i.e., semiconductor sequencing). 9 Microarray technology can also be used to quantify DNA.…”

mentioning

confidence: 99%

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Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

Gregg

Skotko

Benkendorf

et al. 2016

Genetics in Medicine

565

560

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guidelines and statements have assisted patients seeking prenatal screening information and health-care providers responsible for providing accurate and up-to-date information to their patients. [1][2][3] Until recently, noninvasive prenatal screening for aneuploidy relied on measurements of maternal serum analytes and/or ultrasonography. These have a false-positive rate of approximately 5% and detection rates of 50-95%, depending on the specific screening strategy used. Advances in genomic technologies led to noninvasive prenatal screening that relies on the presence of cell-free DNA derived from the placenta but circulating in maternal blood, which is referred to here as noninvasive prenatal screening (NIPS). Massive parallel sequencing of maternal and placental (also called fetal when speaking of the fraction of this DNA in maternal blood) fragments of DNA occurs simultaneously. Sequencing with quantification can be random, targeted, and followed by quantification or exploitation of single-nucleotide polymorphisms. [4][5][6][7][8] Alternatively, sequencing can take place by measuring the release of hydrogen ions as nucleotides are added to a DNA template (i.e., semiconductor sequencing). 9 Microarray technology can also be used to quantify DNA. 10 Bioinformatics that enable these methodologies is complex and proprietary. Since the introduction of NIPS in 2011, health-care providers and patients have experienced marketing pressures, rapidly evolving professional practice guidelines, and confusion regarding the appropriate role of Noninvasive prenatal screening using cell-free DNA (NIPS) has been rapidly integrated into prenatal care since the initial American College of Medical Genetics and Genomics (ACMG) statement in 2013. New evidence strongly suggests that NIPS can replace conventional screening for Patau, Edwards, and Down syndromes across the maternal age spectrum, for a continuum of gestational age beginning at 9-10 weeks, and for patients who are not significantly obese. This statement sets forth a new framework for NIPS that is supported by information from validation and clinical utility studies. Pretest counseling for NIPS remains crucial; however, it needs to go beyond discussions of Patau, Edwards, and Down syndromes. The use of NIPS to include sex chromosome aneuploidy screening and screening for selected copy-number variants (CNVs) is becoming commonplace because there are no other screening options to identify these conditions. Providers should have a more thorough understanding of patient preferences and be able to educate about the current drawbacks of NIPS across the prenatal screening spectrum. Laboratories are encouraged to meet the needs of providers and their patients by delivering meaningful screening reports and to engage in education. With health-care-provider guidance, the patient should be able to make an educated decision about the current use of NIPS and the ramifications of a positive, negative, or no-call result. Genet Med advance online publication 28 July 2016Key Words: cell-f...

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Section: Acmg Statementsupporting

confidence: 59%

mentioning

confidence: 99%

Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

Gregg

Skotko

Benkendorf

et al. 2016

Genetics in Medicine

565

560

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“…Several publications in 2011 noted this difficulty in determining aneuploidy in chromosomes 18 and 13, for example [13,14] . To correct for such variation, we have utilized a chromosome ratio, where the count of mapped sites for a given chromosome of interest (e.g., chromosome 21) is normalized to cumulative counts observed on a predetermined set of custom chromosomes.…”

Section: Optimized Chromosome Quantificationmentioning

confidence: 99%

Non-invasive prenatal testing for fetal aneuploidy by massively parallel DNA sequencing of maternal plasma: the future has arrived today/Nicht-invasiver Pränatal-Test auf fetale Aneuploidie mittels massiv-paralleler DNA-Sequenzanalyse im mütterlichen Plasma: in der Zukunft angekommen

Swanson

Coffeen

Sehnert

2012

Laboratoriumsmedizin

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: After decades of research, non-invasive prenatal testing (NIPT) using maternal blood to determine fetal chromosome status has found its way from the research laboratory into clinical practice, triggering a long-awaited paradigm shift in prenatal care. A variety of methods using sequencing of maternal cell-free DNA (cfDNA) have now been studied, primarily demonstrating their ability to detect the most common fetal aneuploidy, trisomy 21 (T21). The focus of this article is on massively parallel sequencing (MPS) with optimized sequence tag mapping and chromosome quantification, which accurately detects T21 as well as multiple other aneuploidies across the genome. The power of this technique resides in its high precision and reduction of variation within and between sequencing runs. Using MPS, classification of aneuploidy status for a given sample can be reliably assigned from the genetic information alone without the need to factor in other maternal pre-test risk or other clinical variables. Performance of this method has been prospectively demonstrated in a rigorous, blinded, multi-center study in the United States. The findings suggest that MPS can be incorporated into existing prenatal screening algorithms to reduce unnecessary invasive procedures. This technology and key considerations for clinical implementation are discussed.Keywords: cell-free DNA (cfDNA); fetal aneuploidy; massively parallel sequencing (MPS); maternal plasma; noninvasive prenatal testing (NIPT) .Zusammenfassung : Nach jahrzehntelanger Forschung hat der Nicht-invasive Pr ä natal-Test (NIPT) des fetalen Chromosomenstatus im m ü tterlichen Plasma seinen Weg aus den Forschungslaboren in die klinische Praxis gefunden und l ö st einen lange herbeigesehnten Paradigmenwechsel in der pr ä natalen Diagnostik aus. Es wurde bereits eine Vielzahl von Methoden, welche die Sequenzanalyse von m ü tterlicher zell-freier DNA (cfDNA) verwenden, untersucht. Dabei zeigte sich, dass dieser Ansatz f ü r den Nachweis der h ä ufigsten fetalen Aneuploidie, der Trisomie 21 (T21) genutzt werden kann. Der Fokus dieses Artikels liegt auf der massiv-parallelen Sequenzanalyse (MPS) mit optimiertem "Sequence Tag Mapping " und Chromosomenquantifizierung, wodurch T21 und zahlreiche andere Aneuploidie im Genom exakt nachgewiesen werden k ö nnen. Der Vorteil dieser Methode liegt in ihrer hohen Pr ä zision und der Reduzierung der Variation innerhalb eines sowie zwischen mehreren Sequenzierungsl ä ufen. Durch die Verwendung von MPS kann der Aneuploidie-Status einer Probe zuverl ä ssig allein aus der genetischen Information ohne die Fakturierung in anderen m ü tterlichen Pr ä test-Risiko oder anderen klinischen Variablen ermittelt werden. Die Eignung dieser Methode konnte prospektiv in einer streng verblindeten, multizentrischen Studie in den USA demonstriert werden. Die Ergebnisse deuten darauf hin, dass MPS in existierende pr ä natale Screening-Algorithmen integriert werden kann und somit unn ö tige invasive Eingriffe reduziert werden k ö nnen. Die Technologie und ih...

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“…Several recent studies have demonstrated that the most effective screening method for trisomy 21, with a detection rate of more than 99% and false-positive rate of about 0.1%, is derived from examination of cell-free DNA (cf DNA) in maternal plasma [4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis

Kotsopoulou¹,

Tsoplou²,

Mavrommatis

et al. 2015

Diagnosis

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With the discovery of existing circulating cellfree fetal DNA (ccffDNA) in maternal plasma and the advent of next-generation sequencing (NGS) technology, there is substantial hope that prenatal diagnosis will become a predominately non-invasive process in the future. At the moment, non-invasive prenatal testing (NIPT) is available for high-risk pregnancies with significant better sensitivity and specificity than the other existing non-invasive methods (biochemical and ultrasonographical). Mainly it is performed by NGS methods in a few commercial labs worldwide. However, it is expected that many other labs will offer analogous services in the future in this fastgrowing field with a multiplicity of in-house methods (e.g., epigenetic, etc.). Due to various limitations of the available methods and technologies that are explained in detail in this manuscript, NIPT has not become diagnostic yet and women may still need to undergo risky invasive procedures to verify a positive finding or to secure (or even expand) a negative one. Efforts have already started to make the NIPT technologies more accurate (even at the level of a complete fetal genome) and cheaper and thus more affordable, in order to become diagnostic screening tests for all pregnancies in the near future.

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Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting

Cited by 426 publications

References 23 publications

Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

Non-invasive prenatal testing for fetal aneuploidy by massively parallel DNA sequencing of maternal plasma: the future has arrived today/Nicht-invasiver Pränatal-Test auf fetale Aneuploidie mittels massiv-paralleler DNA-Sequenzanalyse im mütterlichen Plasma: in der Zukunft angekommen

Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis

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