scholarly journals Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies

2014 ◽  
Vol 34 (4) ◽  
pp. 335-340 ◽  
Author(s):  
Xuan Huang ◽  
Jing Zheng ◽  
Min Chen ◽  
Yangyu Zhao ◽  
Chunlei Zhang ◽  
...  
Keyword(s):  
Massively Parallel Sequencing ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Massively Parallel ◽  
Plasma Dna ◽  
Noninvasive Prenatal Testing ◽  
Parallel Sequencing ◽  
Twin Pregnancies

scholarly journals Combined Count- and Size-Based Analysis of Maternal Plasma DNA for Noninvasive Prenatal Detection of Fetal Subchromosomal Aberrations Facilitates Elucidation of the Fetal and/or Maternal Origin of the Aberrations

2017 ◽  
Vol 63 (2) ◽  
pp. 495-502 ◽  
Author(s):  
Stephanie C Y Yu ◽  
Peiyong Jiang ◽  
K C Allen Chan ◽  
Brigitte H W Faas ◽  
Kwong W Choy ◽  
...  
Keyword(s):  
Massively Parallel Sequencing ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Massively Parallel ◽  
Test Cases ◽  
Plasma Dna ◽  
Diagnostic Specificity ◽  
Noninvasive Prenatal Testing ◽  
Prenatal Detection ◽  
Positive Results

Abstract BACKGROUND Noninvasive prenatal detection of fetal subchromosomal copy number aberrations (CNAs) can be achieved through massively parallel sequencing of maternal plasma DNA. However, when a mother herself is a carrier of a CNA, one cannot discern if her fetus has inherited the CNA. In addition, false-positive results would become more prevalent when more subchromosomal regions are analyzed. METHODS We used a strategy that combined count- and size-based analyses of maternal plasma DNA for the detection of fetal subchromosomal CNAs in 7 target regions for 10 test cases. RESULTS For the 5 cases in which CNAs were present only in the fetus, the size-based approach confirmed the aberrations detected by the count-based approach. For the 5 cases in which the mother herself carried an aberration, we successfully deduced that 3 of the fetuses had inherited the aberrations and that the other 2 fetuses had not inherited the aberrations. No false positives were observed in this cohort. CONCLUSIONS Combined count- and size-based analysis of maternal plasma DNA permits the noninvasive elucidation of whether a fetus has inherited a CNA from its mother who herself is a carrier of the CNA. This strategy has the potential to improve the diagnostic specificity of noninvasive prenatal testing.

scholarly journals Noninvasive Prenatal Diagnosis of Monogenic Diseases by Targeted Massively Parallel Sequencing of Maternal Plasma: Application to β-Thalassemia

2012 ◽  
Vol 58 (10) ◽  
pp. 1467-1475 ◽  
Author(s):  
Kwan-Wood G Lam ◽  
Peiyong Jiang ◽  
Gary J W Liao ◽  
K C Allen Chan ◽  
Tak Y Leung ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Massively Parallel Sequencing ◽  
Globin Gene ◽  
Maternal Plasma ◽  
Massively Parallel ◽  
Sequencing Data ◽  
Plasma Dna ◽  
Parallel Sequencing ◽  
Noninvasive Prenatal Diagnosis ◽  
Monogenic Diseases

Abstract BACKGROUND A genomewide genetic and mutational profile of a fetus was recently determined via deep sequencing of maternal plasma DNA. This technology could have important applications for noninvasive prenatal diagnosis (NIPD) of many monogenic diseases. Relative haplotype dosage (RHDO) analysis, a core step of this procedure, would allow one to elucidate the maternally inherited half of the fetal genome. For clinical applications, the cost and complexity of data analysis might be reduced via targeted application of this approach to selected genomic regions containing disease-causing genes. There is thus a need to explore the feasibility of performing RHDO analysis in a targeted manner. METHODS We performed target enrichment by using solution-phase hybridization followed by massively parallel sequencing of the β-globin gene region in 2 families undergoing prenatal diagnosis for β-thalassemia. We used digital PCR strategies to physically deduce parental haplotypes. Finally, we performed RHDO analysis with target-enriched sequencing data and parental haplotypes to reveal the β-thalassemic status for the fetuses. RESULTS A mean sequencing depth of 206-fold was achieved in the β-globin gene region by targeted sequencing of maternal plasma DNA. RHDO analysis was successful for the sequencing data obtained from the target-enriched samples, including a region in one of the families in which the parents had similar haplotype structures. Data analysis revealed that both fetuses were heterozygous carriers of β-thalassemia. CONCLUSIONS Targeted sequencing of maternal plasma DNA for NIPD of monogenic diseases is feasible.

scholarly journals Maternal Plasma DNA Analysis with Massively Parallel Sequencing by Ligation for Noninvasive Prenatal Diagnosis of Trisomy 21

2010 ◽  
Vol 56 (3) ◽  
pp. 459-463 ◽  
Author(s):  
Rossa WK Chiu ◽  
Hao Sun ◽  
Ranjit Akolekar ◽  
Christopher Clouser ◽  
Clarence Lee ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Trisomy 21 ◽  
Massively Parallel Sequencing ◽  
Maternal Plasma ◽  
Chromosome 21 ◽  
Massively Parallel ◽  
Plasma Dna ◽  
Parallel Sequencing ◽  
Noninvasive Prenatal Diagnosis ◽  
Sequencing By Synthesis

Abstract Background: Noninvasive prenatal diagnosis of trisomy 21 (T21) has recently been shown to be achievable by massively parallel sequencing of maternal plasma on a sequencing-by-synthesis platform. The quantification of several other human chromosomes, including chromosomes 18 and 13, has been shown to be less precise, however, with quantitative biases related to the chromosomal GC content. Methods: Maternal plasma DNA from 10 euploid and 5 T21 pregnancies was sequenced with a sequencing-by-ligation approach. We calculated the genomic representations (GRs) of sequenced reads from each chromosome and their associated measurement CVs and compared the GRs of chromosome 21 (chr21) for the euploid and T21 pregnancies. Results: We obtained a median of 12 × 106 unique reads (21% of the total reads) per sample. The GRs deviated from those expected for some chromosomes but in a manner different from that previously reported for the sequencing-by-synthesis approach. Measurements of the GRs for chromosomes 18 and 13 were less precise than for chr21. z Scores of the GR of chr21 were increased in the T21 pregnancies, compared with the euploid pregnancies. Conclusions: Massively parallel sequencing-by-ligation of maternal plasma DNA was effective in identifying T21 fetuses noninvasively. The quantitative biases observed among the GRs of certain chromosomes were more likely based on analytical factors than biological factors. Further research is needed to enhance the precision for measuring for the representations of chromosomes 18 and 13.

Noninvasive prenatal testing of fetal aneuploidies by massively parallel sequencing in a prospective Chinese population

2013 ◽  
Vol 33 (7) ◽  
pp. 700-706 ◽  
Author(s):  
Yijun Song ◽  
Congcong Liu ◽  
Hong Qi ◽  
Yunping Zhang ◽  
Xuming Bian ◽  
...  
Keyword(s):  
Chinese Population ◽  
Massively Parallel Sequencing ◽  
Prenatal Testing ◽  
Massively Parallel ◽  
Noninvasive Prenatal Testing ◽  
Parallel Sequencing ◽  
Fetal Aneuploidies

scholarly journals Targeted Massively Parallel Sequencing of Maternal Plasma DNA Permits Efficient and Unbiased Detection of Fetal Alleles

2011 ◽  
Vol 57 (1) ◽  
pp. 92-101 ◽  
Author(s):  
Gary JW Liao ◽  
Fiona MF Lun ◽  
Yama WL Zheng ◽  
KC Allen Chan ◽  
Tak Y Leung ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Massively Parallel Sequencing ◽  
Maternal Plasma ◽  
Targeted Sequencing ◽  
Massively Parallel ◽  
Target Enrichment ◽  
Plasma Dna ◽  
Parallel Sequencing ◽  
Fetal Dna ◽  
Genomic Regions

BACKGROUND Massively parallel sequencing has recently been used in noninvasive prenatal diagnosis. The current costs of this technology are still relatively expensive, however, and sample throughput is still relatively low when it is used as a molecular diagnostic tool. Rather than nonselectively sequencing the genome, target enrichment provides a logical approach for more efficient and cost-effective massively parallel sequencing because it increases the proportion of informative data from the targeted region(s). Existing applications of targeted sequencing have mainly been qualitative analyses of genomic DNA. In this study, we investigated its applicability in enriching selected genomic regions from plasma DNA and the quantitative performance of this approach. METHODS DNA was extracted from plasma samples collected from 12 pregnant women carrying female fetuses. The SureSelect Target Enrichment System (Agilent Technologies) was used to enrich for exons on chromosome X. Plasma DNA libraries with and without target enrichment were analyzed by massively parallel sequencing. Genomic DNA samples of the mother and fetus for each case were genotyped by microarray. RESULTS For the regions targeted by the enrichment kit, the mean sequence coverage of the enriched samples was 213-fold higher than that of the nonenriched samples. Maternal and fetal DNA molecules were enriched evenly. After target enrichment, the coverage of fetus-specific alleles within the targeted region increased from 3.5% to 95.9%. CONCLUSIONS Targeted sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles at genomic regions of interest and is a powerful method for measuring the proportion of fetal DNA in a maternal plasma sample.

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