Efficacy of copy-number variation sequencing technology in prenatal diagnosis

2019 ◽  
Vol 47 (6) ◽  
pp. 651-655 ◽  
Author(s):  
Xiaoxi Zhao ◽  
Lin Fu
Keyword(s):  
Prenatal Diagnosis ◽  
Copy Number Variation ◽  
Copy Number ◽  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Balanced Translocation ◽  
Combined Application ◽  
Number Variation ◽  
Medical University

Abstract Background Classical karyotyping and copy-number variation sequencing (CNV-seq) are useful methods for the prenatal detection of chromosomal abnormalities. Here, we examined the potential of using a combination of the two methods for improved and accurate diagnosis. Methods From February 2013 to January 2018, 64 pregnant women showing indications for fetal chromosomal examination in the affiliated hospital of the Inner Mongolia Medical University were selected for this study. Amniotic fluid was collected and used for karyotype analysis and CNV-seq. Results Karyotype analysis of the 64 cases showed that six cases (9.38%) had chromosomal abnormalities. Using CNV-seq, in addition to three cases with numerical abnormalities of chromosomes, 14 cases were detected with CNV, of which five were pathogenic CNV, four were of uncertain clinical significance and five were polymorphic CNV. However, CNV-seq failed to detect one case with sex chromosome mosaicism and a balanced translocation carrier. The rate of abnormal chromosome and CNV detection was 26.56% (17/64) by CNV-seq. Conclusion Application of CNV-seq in prenatal diagnosis could allow the detection of submicroscopic chromosomal abnormalities and effectively reduce the birth of children with microdeletion and microduplication syndrome. Additionally, the combined application of karyotype analysis and CNV-seq can effectively improve the detection rate of chromosome abnormalities.

Application of Copy Number Variation Sequencing in Genetic Analysis of Miscarriages in Early and Middle Pregnancy

2020 ◽  
Vol 160 (11-12) ◽  
pp. 634-642
Author(s):  
Shiqiang Luo ◽  
Xingyuan Chen ◽  
Tizhen Yan ◽  
Jiaolian Ya ◽  
Zehui Xu ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
High Throughput ◽  
Copy Number ◽  
High Throughput Sequencing ◽  
Chromosomal Abnormalities ◽  
Pregnancy Termination ◽  
Mendelian Inheritance ◽  
Copy Number Variations ◽  
Abnormal Chromosome ◽  
Number Variation

High-throughput sequencing based on copy number variation (CNV-seq) is commonly used to detect chromosomal abnormalities. This study identifies chromosomal abnormalities in aborted embryos/fetuses in early and middle pregnancy and explores the application value of CNV-seq in determining the causes of pregnancy termination. High-throughput sequencing was used to detect chromosome copy number variations (CNVs) in 116 aborted embryos in early and middle pregnancy. The detection data were compared with the Database of Genomic Variants (DGV), the Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER), and the Online Mendelian Inheritance in Man (OMIM) database to determine the CNV type and the clinical significance. High-throughput sequencing results were successfully obtained in 109 out of 116 specimens, with a detection success rate of 93.97%. In brief, there were 64 cases with abnormal chromosome numbers and 23 cases with CNVs, in which 10 were pathogenic mutations and 13 were variants of uncertain significance. An abnormal chromosome number is the most important reason for embryo termination in early and middle pregnancy, followed by pathogenic chromosome CNVs. CNV-seq can quickly and accurately detect chromosome abnormalities and identify microdeletion and microduplication CNVs that cannot be detected by conventional chromosome analysis, which is convenient and efficient for genetic etiology diagnosis in miscarriage.

scholarly journals 8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families

2010 ◽  
Vol 3 (1) ◽  
pp. 3 ◽  
Author(s):  
John CK Barber ◽  
Dave Bunyan ◽  
Merryl Curtis ◽  
Denise Robinson ◽  
Susanne Morlot ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Copy Number Variation ◽  
Copy Number ◽  
Number Variation ◽  
Duplication Syndrome

scholarly journals Analysis of Genomic Copy Number Variation in Miscarriages During Early and Middle Pregnancy

2021 ◽  
Vol 12 ◽  
Author(s):  
Heming Wu ◽  
Qingyan Huang ◽  
Xia Zhang ◽  
Zhikang Yu ◽  
Zhixiong Zhong
Keyword(s):  
Prenatal Diagnosis ◽  
Old Age ◽  
Chromosomal Abnormality ◽  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Copy Number Variations ◽  
Variants Of Unknown Significance ◽  
Number Variation ◽  
Structural Chromosomal Abnormality ◽  
Numerical Chromosomal Abnormality

The purpose of this study was to explore the copy number variations (CNVs) associated with miscarriage during early and middle pregnancy and provide useful genetic guidance for pregnancy and prenatal diagnosis. A total of 505 fetal specimens were collected and CNV sequencing (CNV-seq) analysis was performed to determine the types and clinical significance of CNVs, and relevant medical records were collected. The chromosomal abnormality rate was 54.3% (274/505), among which the numerical chromosomal abnormality rate was 40.0% (202/505) and structural chromosomal abnormality rate was 14.3% (72/505). Chromosomal monosomy mainly occurred on sex chromosomes, and chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 15, 13, and 9. The incidence of numerical chromosomal abnormalities in ≥35 year-old age pregnant women was significantly higher than <35 year-old age group. The highest incidence of pathogenic CNV (pCNV) was found in fetuses at ≤6 weeks of pregnancy (5.26%), and the incidence of variants of unknown significance (VOUS) CNVs decreased gradually with the increase of gestational age. The rate of chromosomal abnormalities of fetuses in early pregnancy (59.5%) was higher than that of fetuses in middle pregnancy (27.2%) (p < 0.001). There were 168 genes in VOUS + pCNV regions. 41 functions and 12 pathways (p < 0.05) were enriched of these genes by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Some meaningful genetic etiology information such as genes and pathways has been obtained, it may provide useful genetic guidance for pregnancy and prenatal diagnosis.

scholarly journals Prenatal diagnosis of 913 fetuses samples using copy number variation sequencing

2021 ◽  
Author(s):  
Liubing Lan ◽  
Lingna She ◽  
Bosen Zhang ◽  
Yanhong He ◽  
Zhiyuan Zheng
Keyword(s):  
Prenatal Diagnosis ◽  
Copy Number Variation ◽  
Copy Number ◽  
Number Variation

scholarly journals Copy Number Assessment by Competitive PCR with Limiting Deoxynucleotide Triphosphates and High-Resolution Melting

2015 ◽  
Vol 61 (5) ◽  
pp. 724-733 ◽  
Author(s):  
Luming Zhou ◽  
Robert A Palais ◽  
Christian N Paxton ◽  
Katherine B Geiersbach ◽  
Carl T Wittwer
Keyword(s):  
Copy Number Variation ◽  
Motor Neuron ◽  
Copy Number ◽  
Sex Chromosome ◽  
Melting Curve ◽  
Growth Factor Receptor ◽  
Relative Quantification ◽  
Pcr Products ◽  
Number Variation ◽  
Survival Of Motor Neuron

Abstract BACKGROUND DNA copy number variation is associated with genetic disorders and cancer. Available methods to discern variation in copy number are typically costly, slow, require specialized equipment, and/or lack precision. METHODS Multiplex PCR with different primer pairs and limiting deoxynucleotide triphosphates (dNTPs) (3–12 μmol/L) were used for relative quantification and copy number assessment. Small PCR products (50–121 bp) were designed with 1 melting domain, well-separated Tms, minimal internal sequence variation, and no common homologs. PCR products were displayed as melting curves on derivative plots and normalized to the reference peak. Different copy numbers of each target clustered together and were grouped by unbiased hierarchical clustering. RESULTS Duplex PCR of a reference gene and a target gene was used to detect copy number variation in chromosomes X, Y, 13, 18, 21, epidermal growth factor receptor (EGFR), survival of motor neuron 1, telomeric (SMN1), and survival of motor neuron 2, centromeric (SMN2). Triplex PCR was used for X and Y and CFTR exons 2 and 3. Blinded studies of 50 potential trisomic samples (13, 18, 21, or normal) and 50 samples with potential sex chromosome abnormalities were concordant to karyotyping, except for 2 samples that were originally mosaics that displayed a single karyotype after growth. Large cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7) (CFTR) deletions, EGFR amplifications, and SMN1 and SMN2 copy number assessments were also demonstrated. Under ideal conditions, copy number changes of 1.11-fold or lower could be discerned with CVs of about 1%. CONCLUSIONS Relative quantification by restricting the dNTP concentration with melting curve display is a simple and precise way to assess targeted copy number variation.

scholarly journals Clinical diagnosis of single-gene disorders and chromosomal abnormalities based on BGISEQ-500 platform

2019 ◽  
Author(s):  
Yanqiu Liu ◽  
Liangwei Mao ◽  
Xiaoming Wei ◽  
Jianfen Man ◽  
Wenqian Zhang ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Clinical Diagnosis ◽  
High Throughput ◽  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Genomic Copy Number ◽  
Genomic Copy ◽  
Monogenic Diseases ◽  
Number Variation ◽  
Genomic Copy Number Variation

AbstractMost of the variation in the human genome is a single nucleotide variation (SNV) based on a single base or small fragment insertions and deletions and genomic copy number variation (CNV). Both types of mutations are involved in many human diseases. Such diseases often have complex clinical symptoms and difficult clinical diagnosis, so an effective detection method is needed to help clinical diagnosis and prevent birth defects. With the development of sequencing technology, the method of chip capture combined with high-throughput sequencing has been extensively used because of its high throughput, high accuracy, high speed and low cost. This study designed a chip that captures the coding region of 3043 genes associated with 4013 monogenic diseases. In addition, 148 chromosomal abnormalities can be identified by setting targets in specific regions. Compared with the whole exon chip, the chip can detect 4013 monogenic diseases and 148 chromosomal abnormalities at a lower cost, including SNV, intra-gene CNV and genomic copy number variation. This study utilized a strategy of combining the BGISEQ500 sequencing platform with the chip to identify 102 disease-associated mutations in 63 patients, 69 of which were new mutations. The evaluation test results also show that this combination complies with the requirements of clinical testing and has good clinical application value.

A PGD Pregnancy Achieved by Embryo Copy Number Variation Sequencing with Confirmation by Non-Invasive Prenatal Diagnosis

2014 ◽  
Vol 41 (8) ◽  
pp. 453-456 ◽  
Author(s):  
Hui Wang ◽  
Li Wang ◽  
Minyue Ma ◽  
Zhuo Song ◽  
Jianguang Zhang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Copy Number Variation ◽  
Copy Number ◽  
Non Invasive ◽  
Number Variation

scholarly journals Combined Application of Chromosome Karyotype and Microarray Analysis in Fetus With Increased Nuchal Translucency

2021 ◽  
Author(s):  
Wang Chaohong ◽  
Tang Junxiang ◽  
Sun Yuxiu ◽  
Pang Yu ◽  
Tong Keting ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Microarray Analysis ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Nuchal Translucency ◽  
Chromosome Abnormalities ◽  
Detection Rates ◽  
Combined Application ◽  
Chromosome Karyotype

Abstract Objective：To examine the risk of chromosomal abnormalities when the thickness of the nuchal translucency( NT ) is 2.5-2.9mm, to evaluate the cutoff value of NT for prenatal diagnosis, to explore the value of combined application of chromosome karyotype and microarray analysis, and to explore the relationship between NT ≥ 5.0mm and fetal prognosis. Methods：A total of 366 pregnant women who underwent prenatal diagnosis in Anhui Province Maternity and Child Health Hospital from January 2018 to August 2020 were collected, of which 241 cases had NT ≥ 2.5mm, 125 cases were elderly (35-38 years old) with NT < 2.5mm. We made grouping statistics on chromosome abnormalities,and compared the detection of chromosome abnormalities by karyotype and microarray analysis. At the same time, we followed up the fetuses with NT ≥ 5.0mm and analyzed their prognosis. Results: (1)Among the 366 cases with NT thickening,the detection rates of chromosome abnormalities by karyotype analysis and microarray analysis(CMA) were 13.39% (49/366) and 13.93% (51/366), respectively, and there was no significant difference (P>0.05), including 25 cases of trisomy 21, 5 cases of trisomy 18, 5 cases of Turner synthesis and 16 cases of other chromosome abnormalities. (2)We compared the effect of different NT value on the detection rate of pathogenic chromosomes, and found that the difference between NT ≥2.5mm and NT < 2.5mm was statistically significant(P<0.05). The detection rates of pathogenic chromosomal abnormalities in NT < 2.5mm group,2.5-2.9mm group, 3.0-3.4mm group,3.5-4.4mm group,4.5-5.4mm group and NT ≥ 5.5mm group were 0.8%(1/ 125), 11.63%(10/ 86), 17.81%(13/ 73), 20%(10/ 49), 47.62%(10/ 21) and 63.64%(7/ 11) respectively. (3)Our study found that different prenatal diagnostic indicators for abnormal chromosome detection rate difference was statistically significant(P<0.05). The detection rates of NT thickening alone and NT thickening combined with other abnormalities were 13.17%(22/ 167) and 35.14%(26/ 74) respectively(P<0.05). (4)Among 18 pregnant women with NT ≥ 5.0 mm, 9 fetuses were chromosomal abnormalities, and 9 fetuses survived healthily. Conclusions：When the NT value is 2.5-2.9mm, the incidence of fetal chromosome abnormality is significantly higher than that in the normal group. It is suggested that invasive prenatal diagnosis should be performed for pregnant women with NT ≥ 2.5mm. Chromosome karyotype analysis and CMA can complement each other, which is conducive to prenatal genetic counseling. The fetuses with NT thickening usually have good pregnancy outcomes when excluding fetal chromosome and prenatal ultrasound does not indicate any abnormalities.

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