scholarly journals Detection of fetal copy number variants by non-invasive prenatal testing for common aneuploidies

2016 ◽  
Vol 47 (1) ◽  
pp. 53-57 ◽  
Author(s):  
R. Li ◽  
J. Wan ◽  
Y. Zhang ◽  
F. Fu ◽  
Y. Ou ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Non Invasive

scholarly journals PREIMPLANTATION GENETIC TESTING: Non-invasive prenatal testing for aneuploidy, copy-number variants and single-gene disorders

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. A1-A11
Author(s):  
J Shaw ◽  
E Scotchman ◽  
N Chandler ◽  
L S Chitty
Keyword(s):  
Copy Number ◽  
Sex Chromosome ◽  
Single Gene ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Aneuploidy Screening ◽  
Preimplantation Genetic Testing ◽  
Non Invasive ◽  
Single Gene Disorders ◽  
Cell Free Fetal Dna

The discovery of cell-free fetal DNA (cffDNA) in maternal plasma has enabled a paradigm shift in prenatal testing, allowing for safer, earlier detection of genetic conditions of the fetus. Non-invasive prenatal testing (NIPT) for fetal aneuploidies has provided an alternative, highly efficient approach to first-trimester aneuploidy screening, and since its inception has been rapidly adopted worldwide. Due to the genome-wide nature of some NIPT protocols, the commercial sector has widened the scope of cell-free DNA (cfDNA) screening to include sex chromosome aneuploidies, rare autosomal trisomies and sub-microscopic copy-number variants. These developments may be marketed as ‘expanded NIPT’ or ‘NIPT Plus’ and bring with them a plethora of ethical and practical considerations. Concurrently, cfDNA tests for single-gene disorders, termed non-invasive prenatal diagnosis (NIPD), have been developed for an increasing array of conditions but are less widely available. Despite the fact that all these tests utilise the same biomarker, cfDNA, there is considerable variation in key parameters such as sensitivity, specificity and positive predictive value depending on what the test is for. The distinction between diagnostics and screening has become blurred, and there is a clear need for the education of physicians and patients regarding the technical capabilities and limitations of these different forms of testing. Furthermore, there is a requirement for consistent guidelines that apply across health sectors, both public and commercial, to ensure that tests are validated and robust and that careful and appropriate pre-test and post-test counselling is provided by professionals who understand the tests offered.

scholarly journals Non-invasive prenatal testing reveals copy number variations related to pregnancy complications

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Guangping Wu ◽  
Rong Li ◽  
Chao Tong ◽  
Miaonan He ◽  
Zhiwei Qi ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Copy Number ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Non Invasive

scholarly journals Validation of Copy Number Variants Detection from Pregnant Plasma Using Low-Pass Whole-Genome Sequencing in Noninvasive Prenatal Testing-Like Settings

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 569
Author(s):  
Michaela Hyblova ◽  
Maria Harsanyova ◽  
Diana Nikulenkov-Grochova ◽  
Jitka Kadlecova ◽  
Marcel Kucharik ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Detection Algorithm ◽  
Detection Sensitivity ◽  
Clinical Settings ◽  
Noninvasive Prenatal Testing ◽  
Low Pass ◽  
Cnv Detection ◽  
Fetal Fraction

Detection of copy number variants as an integral part of noninvasive prenatal testing is increasingly used in clinical practice worldwide. We performed validation on plasma samples from 34 pregnant women with known aberrations using cell-free DNA sequencing to evaluate the sensitivity for copy number variants (CNV) detection using an in-house CNV fraction-based detection algorithm. The sensitivity for CNVs smaller than 3 megabases (Mb), larger than 3Mb, and overall was 78.57%, 100%, and 90.6%, respectively. Regarding the fetal fraction, detection sensitivity in the group with a fetal fraction of less than 10% was 57.14%, whereas there was 100% sensitivity in the group with fetal fraction exceeding 10%. The assay is also capable of indicating whether the origin of an aberration is exclusively fetal or fetomaternal/maternal. This validation demonstrated that a CNV fraction-based algorithm was applicable and feasible in clinical settings as a supplement to testing for common trisomies 21, 18, and 13.

scholarly journals Expanding the application of non-invasive prenatal testing in the detection of foetal chromosomal copy number variations

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chaohong Wang ◽  
Junxiang Tang ◽  
Keting Tong ◽  
Daoqi Huang ◽  
Huayu Tu ◽  
...  
Keyword(s):  
Copy Number ◽  
Prenatal Testing ◽  
Trisomy 13 ◽  
Clinical Samples ◽  
Chromosomal Microarray Analysis ◽  
True Positive ◽  
Predictive Values ◽  
Non Invasive ◽  
Chromosome Aneuploidy

Abstract Purpose The aim of this study was to assess the detection efficiency and clinical application value of non-invasive prenatal testing (NIPT) for foetal copy number variants (CNVs) in clinical samples from 39,002 prospective cases. Methods A total of 39,002 pregnant women who received NIPT by next-generation sequencing (NGS) with a sequencing depth of 6 M reads in our centre from January 2018 to April 2020 were enrolled. Chromosomal microarray analysis (CMA) was further used to diagnose suspected chromosomal aneuploidies and chromosomal microdeletion/microduplication for consistency assessment. Results A total of 473 pregnancies (1.213%) were positive for clinically significant foetal chromosome abnormalities by NIPT. This group comprised 99 trisomy 21 (T21, 0.254%), 30 trisomy 18 (T18, 0.077%), 25 trisomy 13 (T13, 0.064%), 155 sex chromosome aneuploidy (SCA, 0.398%), 69 rare trisomy (0.177%), and 95 microdeletion/microduplication syndrome (MMS, 0.244%) cases. Based on follow-up tests, the positive predictive values (PPVs) for the T21, T18, T13, SCA, rare trisomy, and MMS cases were calculated to be 88.89%, 53.33%, 20.00%, 40.22%, 4.88%, and 49.02%, respectively. In addition, the PPVs of CNVs of < 5 Mb, 5–10 Mb, and > 10 Mb were 54.55%, 38.46%, and 40.00%, respectively. Among the 95 cases with suspected CNVs, 25 were diagnosed as true positive and 26 cases as false positive; follow-up prenatal diagnosis by CMA was not performed for 44 cases. Moreover, among the 25 true positive cases, 10 were pathogenic, 3 were likely pathogenic, and 12 were of uncertain significance. Conclusion NIPT is not only suitable for screening T21, T18, T13, and SCA but also has potential significance for CNV detection. As combined with ultrasound, extended NIPT is effective for screening MMS. However, NIPT should not be recommended for whole-chromosome aneuploidy screening.

scholarly journals Clinical Validation of a Non-Invasive Prenatal Test for Genome-Wide Detection of Fetal Copy Number Variants

2015 ◽  
Author(s):  
Roy B Lefkowitz ◽  
John A Tynan ◽  
Tong Liu ◽  
Yijin Wu ◽  
Amin R Mazloom ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Copy Number Variants ◽  
Trisomy 13 ◽  
Clinical Validation ◽  
Fetal Sex ◽  
Non Invasive ◽  
Genome Wide ◽  
Wide Range

Background: Current cell-free DNA (cfDNA) assessment of fetal chromosomes does not analyze and report on all chromosomes. Hence, a significant proportion of fetal chromosomal abnormalities are not detectable by current non-invasive methods. Here we report the clinical validation of a novel NIPT designed to detect genome-wide gains and losses of chromosomal material ≥7 Mb and losses associated with specific deletions <7 Mb. Objective: The objective of this study is to provide a clinical validation of the sensitivity and specificity of a novel NIPT for detection of genome-wide abnormalities. Study Design: This retrospective, blinded study included maternal plasma collected from 1222 study subjects with pregnancies at increased risk for fetal chromosomal abnormalities that were assessed for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), fetal sex, genome-wide copy number variants (CNVs) 7 Mb and larger, and select deletions smaller than 7 Mb. Performance was assessed by comparing test results with findings from G-band karyotyping, microarray data, or high coverage sequencing. Results: Clinical sensitivity within this study was determined to be 100% for T21, T18, T13, and SCAs, and 97.7% for genome-wide CNVs. Clinical specificity within this study was determined to be 100% for T21, T18, and T13, and 99.9% for SCAs and CNVs. Fetal sex classification had an accuracy of 99.6%. Conclusion: This study has demonstrated that genome-wide non-invasive prenatal testing (NIPT) for fetal chromosomal abnormalities can provide high resolution, sensitive, and specific detection of a wide range of sub-chromosomal and whole chromosomal abnormalities that were previously only detectable by invasive karyotype analysis. In some instances, this NIPT also provided additional clarification about the origin of genetic material that had not been identified by invasive karyotype analysis.

scholarly journals Identification of Structural Variation from NGS-Based Non-Invasive Prenatal Testing

2019 ◽  
Vol 20 (18) ◽  
pp. 4403 ◽  
Author(s):  
Ondrej Pös ◽  
Jaroslav Budis ◽  
Zuzana Kubiritova ◽  
Marcel Kucharik ◽  
Frantisek Duris ◽  
...  
Keyword(s):  
Genetic Diseases ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Genomic Data ◽  
Population Diversity ◽  
Clinical Diagnostics ◽  
Plasma Dna ◽  
Non Invasive ◽  
Slovak Population ◽  
Pathogenic Variants

Copy number variants (CNVs) are an important type of human genome variation, which play a significant role in evolution contribute to population diversity and human genetic diseases. In recent years, next generation sequencing has become a valuable tool for clinical diagnostics and to provide sensitive and accurate approaches for detecting CNVs. In our previous work, we described a non-invasive prenatal test (NIPT) based on low-coverage massively parallel whole-genome sequencing of total plasma DNA for detection of CNV aberrations ≥600 kbp. We reanalyzed NIPT genomic data from 5018 patients to evaluate CNV aberrations in the Slovak population. Our analysis of autosomal chromosomes identified 225 maternal CNVs (47 deletions; 178 duplications) ranging from 600 to 7820 kbp. According to the ClinVar database, 137 CNVs (60.89%) were fully overlapping with previously annotated variants, 66 CNVs (29.33%) were in partial overlap, and 22 CNVs (9.78%) did not overlap with any previously described variant. Identified variants were further classified with the AnnotSV method. In summary, we identified 129 likely benign variants, 13 variants of uncertain significance, and 83 likely pathogenic variants. In this study, we use NIPT as a valuable source of population specific data. Our results suggest the utility of genomic data from commercial CNV analysis test as background for a population study.

scholarly journals Expanded Noninvasive Prenatal Testing for Chromosomal aneuploidies and Copy Number Variants in a Cohort of 16128 Single Pregnancies

2021 ◽  
Author(s):  
Jing He ◽  
Xuan Feng ◽  
Xing Wang ◽  
Qinghua Zhang ◽  
Lei Zheng ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
True Positive ◽  
Noninvasive Prenatal Testing ◽  
Cell Free Fetal Dna ◽  
Monogenic Diseases ◽  
Positive Rate ◽  
Chromosomal Aneuploidies

Abstract Background: Noninvasive prenatal testing (NIPT) is based on second-generation genomic sequencing technology to scan cell-free fetal DNA originating from the placenta in maternal plasma. As the depth of sequencing increases, it can be used to focus on chromosomal aneuploidies, copy number variants (CNVs), and monogenic diseases. It can significantly improve the accuracy of prenatal screening and reduces the number of invasive testing.Methods: In this study, we retrospectively analyzed 16128 naturally conceived singleton pregnancies who underwent expanded NIPT to calculate the true positive rate (TPR) of chromosomal aneuploidies and CNVs, and analyzed the potential influence of maternal sex chromosome abnormalities (SCAs) and maternal CNVs on expanded NIPT results.Results: After invasive prenatal diagnosis and follow-up, 103 pregnancies were found to be true-positive, including 73 cases of chromosomal abnormalities and 30 cases of CNVs. The TPR of T21 was 84.62%, T18 was 50.00%, T13 was 22.22%, SCA was 34.06%, and CNVs was 40.28%. In addition, we found that the positive rate of aneuploidies increased with maternal age and that maternal SCAs accounted for 13.33% of the 60 false positive cases of SCAs.Conclusion: Expanded NIPT showed high sensitivity and specificity in detecting diseases of chromosomal abnormalities. It also shows good performance in detecting CNVs, but maternal SCAs and CNVs confused some NIPT results, indicating it is still necessary to study the potential maternal influence on expanded NIPT results and to report related clinical validation studies.

scholarly journals Expanding the Scope of Non-invasive Prenatal Testing to Detect Fetal Chromosomal Copy Number Variations

2021 ◽  
Vol 8 ◽  
Author(s):  
Songchang Chen ◽  
Lanlan Zhang ◽  
Jiong Gao ◽  
Shuyuan Li ◽  
Chunxin Chang ◽  
...  
Keyword(s):  
Copy Number ◽  
Detection Rate ◽  
Prenatal Testing ◽  
Read Depth ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Non Invasive ◽  
Positive Detection Rate ◽  
Cnv Detection

Non-invasive prenatal testing (NIPT) for common fetal trisomies is effective. However, the usefulness of cell-free DNA testing to detect other chromosomal abnormalities is poorly understood. We analyzed the positive rate at different read depths in next-generation sequencing (NGS) and identified a strategy for fetal copy number variant (CNV) detection in NIPT. Pregnant women who underwent NIPT by NGS at read depths of 4–6 M and fetuses with suspected CNVs were analyzed by amniocentesis and chromosomal microarray analysis (CMA). These fetus samples were re-sequenced at a read depth of 25 M and the positive detection rate was determined. With the increase in read depth, the positive CNV detection rate increased. The positive CNV detection rates at 25 M with small fragments were higher by NGS than by karyotype analysis. Increasing read depth in NGS improves the positive CNV detection rate while lowering the false positive detection rate. NIPT by NGS may be an accurate method of fetal chromosome analysis and reduce the rate of birth defects.

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