A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study

Dhallan, Ravinder; Guo, Xin; Emche, Sarah; Damewood, Marian D.; Bayliss, Philip; Cronin, Michael J.; Barry, Julie; Betz, Jordan; Franz, Kara; Gold, Katie; Vallecillo, Brett; Varney, John

doi:10.1016/s0140-6736(07)60115-9

Cited by 120 publications

(69 citation statements)

References 22 publications

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“…To achieve a fractional fetal DNA concentration of 25%, methods are needed to allow the selective enrichment of fetal DNA (22) or the suppression of the maternal DNA background (11,23) The number of plasma DNA molecules that are present per unit volume of maternal plasma is limited (8). For example, in early pregnancy, the median maternal plasma concentration of an autosomal locus, the ␤-globin gene, has been shown to be 986 copies per milliliter, with contributions from both the fetus and mother (8).…”

Section: Discussionmentioning

confidence: 99%

“…Second, fetal nucleic acids circulate in maternal plasma in a cell-free form, making it difficult to derive chromosome dosage information. Significant developments have recently been made (9)(10)(11). One approach focuses on the detection of nucleic acid species that are fetal-specific, including DNA fragments with a placenta-specific DNA methylation pattern (10,12) and RNA molecules expressed by the placenta (9).…”

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confidence: 99%

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Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Lun²,

Chan³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

390

328

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Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal diagnostic methods involve the sampling of fetal materials by invasive procedures such as amniocentesis. Screening by ultrasonography and biochemical markers have been used to risk-stratify pregnant women before definitive invasive diagnostic procedures. However, these screening methods generally target epiphenomena, such as nuchal translucency, associated with trisomy 21. It would be ideal if noninvasive genetic methods were available for the direct detection of the core pathology of trisomy 21. Here we outline an approach using digital PCR for the noninvasive detection of fetal trisomy 21 by analysis of fetal nucleic acids in maternal plasma. First, we demonstrate the use of digital PCR to determine the allelic imbalance of a SNP on PLAC4 mRNA, a placenta-expressed transcript on chromosome 21, in the maternal plasma of women bearing trisomy 21 fetuses. We named this the digital RNA SNP strategy. Second, we developed a nonpolymorphism-based method for the noninvasive prenatal detection of trisomy 21. We named this the digital relative chromosome dosage (RCD) method. Digital RCD involves the direct assessment of whether the total copy number of chromosome 21 in a sample containing fetal DNA is overrepresented with respect to a reference chromosome. Even without elaborate instrumentation, digital RCD allows the detection of trisomy 21 in samples containing 25% fetal DNA. We applied the sequential probability ratio test to interpret the digital PCR data. Computer simulation and empirical validation confirmed the high accuracy of the disease classification algorithm.circulating fetal nucleic acids ͉ noninvasive prenatal diagnosis ͉ sequential probability ratio test ͉ trisomy 21 ͉ RNA SNP

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Lun²,

Chan³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

390

328

View full text Add to dashboard Cite

show abstract

“…Cell-free circulating DNA (CFDNA) has been studied in a wide range of physiological and pathological conditions, including pregnancy, trauma, inflammatory disorders and malignancy [1,2]. It is present in normal healthy individuals at low concentrations (ng/ml) [3].…”

Section: Introductionmentioning

confidence: 99%

Optimizing the yield and utility of circulating cell-free DNA from plasma and serum

Xue

Teare

Holen

et al. 2009

Clinica Chimica Acta

139

114

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“…Currently researchers worldwide are trying to develop techniques *Correspondence to: Loes Kooij, Department of Health Sciences, University Medical Centre Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. E-mail: halkooij@xs4all.nl that are to result in accurate testing for fetal aneuploidie (Dhallan et al, 2007). It is quite possible that these tests can already be applied in the first trimester of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

“…The test is relatively simple-a blood sample of the pregnant woman will do-and the diagnose can be given with a high certainty in the first trimester of pregnancy (Dhallan et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The attitude of women toward current and future possibilities of diagnostic testing in maternal blood using fetal DNA

2009

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The attitude of women toward current and future possibilities of diagnostic testing in maternal blood using fetal DNA Kooij, Loes; Tymstra, Tjeerd; van den Berg, Paul Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Objective To determine the opinions of women about the new developments in the field of noninvasive prenatal diagnosis (NIPD).Method Prospective study using questionnaires in two groups of women: women visiting the University Medical Centre Groningen and the Martini Hospital Groningen for the routine fetal anomaly ultrasound scan at 20 weeks' gestation and female medical master students.Results Both groups consider NIPD an important asset in the reliable diagnosis of fetal aneuploidy and gender-determined genetic disorders, with the exception of disorders manifesting themselves later in life. There is a negative response as to its application for family balancing. Eighty-two percent of the pregnant women and 79% of the medical students responded positively to the question whether they consider NIPD an important asset in prenatal care. The statement that it is an asset because it enables pregnant women to bear an 'optimal child' is strongly rejected by both groups.Conclusions NIPD paves the way for screening on a large scale. Our survey shows that women feel positive about these new possibilities, but find it hard to fully realize the consequences and new choices they will be confronted with.

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A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study

Cited by 120 publications

References 22 publications

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Optimizing the yield and utility of circulating cell-free DNA from plasma and serum

The attitude of women toward current and future possibilities of diagnostic testing in maternal blood using fetal DNA

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