Noninvasive prenatal testing goes global.
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ABSTRACT:
SUBMITTER: Chandrasekharan S
PROVIDER: S-EPMC4112725 | biostudies-literature | 2014 Apr
REPOSITORIES: biostudies-literature
Publications
Noninvasive prenatal testing goes global.
Chandrasekharan Subhashini S Minear Mollie A MA Hung Anthony A Allyse Megan M
Science translational medicine 20140401 231
Noninvasive prenatal genetic testing is becoming available worldwide--particularly in low- and middle-income countries--but practical and ethical challenges must be overcome. ...[more]
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Project description: Not available
| S-EPMC4150709 | biostudies-literature
Project description:PurposeThe aim of the study was to evaluate the diagnostic accuracy of an informatics-based, noninvasive, prenatal paternity test using array-based single-nucleotide polymorphism measurements of cell-free DNA isolated from maternal plasma.MethodsBlood samples were taken from 21 adult pregnant women (with gestational ages between 6 and 21 weeks), and a genetic sample was taken from the corresponding biological fathers. Paternity was confirmed by genetic testing of the infant, products of conception, control of fertilization, and/or preimplantation genetic diagnosis during in vitro fertilization. Parental DNA samples and maternal plasma cell-free DNA were amplified and analyzed using a HumanCytoSNP-12 array. An informatics-based method measured single-nucleotide polymorphism data, confirming or rejecting paternity. Each plasma sample with a sufficient fetal cell-free DNA fraction was independently tested against the confirmed father and 1,820 random, unrelated males.ResultsOne of the 21 samples had insufficient fetal cell-free DNA. The test correctly confirmed paternity for the remaining 20 samples (100%) when tested against the biological father, with P values of <10(-4). For the 36,400 tests using an unrelated male as the alleged father, 99.95% (36,382) correctly excluded paternity and 0.05% (18) were indeterminate. There were no miscalls.ConclusionA noninvasive paternity test using informatics-based analysis of single-nucleotide polymorphism array measurements accurately determined paternity early in pregnancy.
| S-EPMC3910294 | biostudies-literature
Project description:Concerns of traditional prenatal aneuploidy testing methods, such as low accuracy of noninvasive and health risks associated with invasive procedures, were overcome with the introduction of novel noninvasive methods based on genetics (NIPT). These were rapidly adopted into clinical practice in many countries after a series of successful trials of various independent submethods. Here we present results of own NIPT trial carried out in Moscow, Russia. 1012 samples were subjected to the method aimed at measuring chromosome coverage by massive parallel sequencing. Two alternative approaches are ascertained: one based on maternal/fetal differential methylation and another based on allelic difference. While the former failed to provide stable results, the latter was found to be promising and worthy of conducting a large-scale trial. One critical point in any NIPT approach is the determination of fetal cell-free DNA fraction, which dictates the reliability of obtained results for a given sample. We show that two different chromosome Y representation measures-by real-time PCR and by whole-genome massive parallel sequencing-are practically interchangeable (r=0.94). We also propose a novel method based on maternal/fetal allelic difference which is applicable in pregnancies with fetuses of either sex. Even in its pilot form it correlates well with chromosome Y coverage estimates (r=0.74) and can be further improved by increasing the number of polymorphisms.
| S-EPMC5054814 | biostudies-literature
Project description:Nowadays it is common sense in obstetrics that an increased risk for pregnancy loss due to invasive testing does not exist. Nonetheless, noninvasive prenatal testing (NIPT) is a hot topic, even though this approach does not provide a reduction of unintentionally induced abortions. NIPT has a number of shortcuts which are highlighted in this review, including: (1) in NIPT placental rather than fetal DNA is studied, (2) NIPT fails in 2-6% of cases, and (3) trisomy 21 accounts for only ∼50% of existing chromosomal aberrations. Thus, we agree with the literature that NIPT is a fascinating possibility to gain information on unborn life from minimal amounts of DNA. However, it remains a pure risk estimation test directed towards the detection of specific chromosomal abnormalities from peripheral blood of the pregnant woman. It is important to highlight that families buying this test, and getting a normal result, may be provided with a false sense of security. Thus, careful and comprehensive genetic counselling should be performed before the test is offered, and should include a clear explanation of the advantages and disadvantages, as well as limitations, compared to other methods.
| S-EPMC6945944 | biostudies-literature
Project description:BackgroundChromosome 18p deletion syndrome is a disease caused by the complete or partial deletion of the short arm of chromosome 18, there were few cases reported about the prenatal diagnosis of 18p deletion syndrome. Noninvasive prenatal testing (NIPT) is widely used in the screening of common fetal chromosome aneuploidy. However, the segmental deletions and duplications should also be concerned. Except that some cases had increased nuchal translucency or holoprosencephaly, most of the fetal phenotype of 18p deletion syndrome may not be evident during the pregnancy, 18p deletion syndrome was always accidentally discovered during the prenatal examination.Case presentationsIn our case, we found a pure partial monosomy 18p deletion during the confirmation of the result of NIPT by copy number variation sequencing (CNV-Seq). The result of NIPT suggested that there was a partial or complete deletion of X chromosome. The amniotic fluid karyotype was normal, but result of CNV-Seq indicated a 7.56 Mb deletion on the short arm of chromosome 18 but not in the couple, which means the deletion was de novo deletion. Finally, the parents chose to terminate the pregnancy.ConclusionsTo our knowledge, this is the first case of prenatal diagnosis of 18p deletion syndrome following NIPT.NIPT combined with ultrasound may be a relatively efficient method to screen chromosome microdeletions especially for the 18p deletion syndrome.
| S-EPMC6925888 | biostudies-literature
Project description:ObjectiveNoninvasive prenatal testing (NIPT) is widely used in clinical detection of fetal autosomal duplications or deletions. The aim of this study was to investigate the clinical application of NIPT for detection of chromosomal microdeletions.MethodsMicrodeletions of about 5 Mb in the long arm of chromosome 15 (q11.2-q12) were detected by NIPT and were confirmed by karyotype analysis and copy number variation (CNV) analysis based on high-throughput sequencing technology.ResultsThe CNV results of prenatal diagnosis showed that there were approximately 4.96 Mb of microdeletions in 15q11.2-q13.1, which was consistent with the NIPT results. The karyotype analysis showed no abnormalities.ConclusionIn this study, the microdeletion fragment of fetal chromosome 15 was successfully detected and diagnosed using NIPT. This suggests that NIPT is an efficient method to gain genetic information about chromosomal abnormalities.
| S-EPMC6642313 | biostudies-literature
Project description:Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring.
| S-EPMC4060699 | biostudies-literature
Project description:OBJECTIVE:To develop a method for noninvasive prenatal paternity testing based on targeted sequencing of single nucleotide polymorphisms (SNPs). METHOD:SNPs were selected based on population genetics data. Target-SNPs in cell-free DNA extracted from maternal blood (maternal cfDNA) were analyzed by targeted sequencing wherein target enrichment was based on multiplex amplification using QIAseq Targeted DNA Panels with Unique Molecular Identifiers. Fetal SNP genotypes were called using a novel bioinformatics algorithm, and the combined paternity indices (CPIs) and resultant paternity probabilities were calculated. RESULTS:Fetal SNP genotypes obtained from targeted sequencing of maternal cfDNA were 100% concordant with those from amniotic fluid-derived fetal genomic DNA. From an initial panel of 356 target-SNPs, an average of 148 were included in paternity calculations in 15 family trio cases, generating paternity probabilities of greater than 99.9999%. All paternity results were confirmed by short-tandem-repeat analysis. The high specificity of the methodology was validated by successful paternity discrimination between biological fathers and their siblings and by large separations between the CPIs calculated for the biological fathers and those for 60 unrelated men. CONCLUSION:The novel method is highly effective, with substantial improvements over similar approaches in terms of reduced number of target-SNPs, increased accuracy, and reduced costs.
| S-EPMC7154534 | biostudies-literature
Project description:ObjectiveThe goal was to develop methods for detection of chromosomal and subchromosomal abnormalities in fetal cells in the mother's circulation at 10-16?weeks' gestation using analysis by array comparative genomic hybridization (CGH) and/or next-generation sequencing (NGS).MethodNucleated cells from 30?mL of blood collected at 10-16?weeks' gestation were separated from red cells by density fractionation and then immunostained to identify cytokeratin positive and CD45 negative trophoblasts. Individual cells were picked and subjected to whole genome amplification, genotyping, and analysis by array CGH and NGS.ResultsFetal cells were recovered from most samples as documented by Y chromosome PCR, short tandem repeat analysis, array CGH, and NGS including over 30 normal male cells, one 47,XXY cell from an affected fetus, one trisomy 18 cell from an affected fetus, nine cells from a trisomy 21 case, three normal cells and one trisomy 13 cell from a case with confined placental mosaicism, and two chromosome 15 deletion cells from a case known by CVS to have a 2.7?Mb de novo deletion.ConclusionWe believe that this is the first report of using array CGH and NGS whole genome sequencing to detect chromosomal abnormalities in fetal trophoblastic cells from maternal blood. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
| S-EPMC5129580 | biostudies-literature
Project description:To the authors' best knowledge, this is the first report of acute myeloid leukemia (AML) detected by noninvasive prenatal testing. This was an aggressive case that otherwise would have been difficult to characterize due to disadvantages of "gold-standard" techniques.
| S-EPMC7562837 | biostudies-literature