scholarly journals Clinical Utility and the Yield of Single Nucleotide Polymorphism Array in Prenatal Diagnosis of Fetal Central Nervous System Abnormalities

2021 ◽  
Vol 8 ◽  
Author(s):  
Meiying Cai ◽  
Hailong Huang ◽  
Liangpu Xu ◽  
Na Lin
Keyword(s):  
Central Nervous System ◽  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Snp Array ◽  
Copy Number Variations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pathogenic Cnvs

Applying single nucleotide polymorphism (SNP) array to identify the etiology of fetal central nervous system (CNS) abnormality, and exploring its association with chromosomal abnormalities, copy number variations, and obstetrical outcome. 535 fetuses with CNS abnormalities were analyzed using karyotype analysis and SNP array. Among the 535 fetuses with CNS abnormalities, chromosomal abnormalities were detected in 36 (6.7%) of the fetuses, which were consistent with karyotype analysis. Further, additional 41 fetuses with abnormal copy number variations (CNVs) were detected using SNP array (the detection rate of additional abnormal CNVs was 7.7%). The rate of chromosomal abnormalities, but not that of pathogenic CNVs in CNS abnormalities with other ultrasound abnormalities was significantly higher than that in isolated CNS abnormalities. The rates of chromosomal abnormalities and pathogenic CNVs in fetuses with spine malformation (50%), encephalocele (50%), subependymal cyst (20%), and microcephaly (16.7%) were higher than those with other isolated CNS abnormalities. The pregnancies for 36 cases with chromosomal abnormalities, 18 cases with pathogenic CNVs, and three cases with VUS CNVs were terminated. SNP array should be used in the prenatal diagnosis of fetuses with CNS abnormalities, which can enable better prenatal assessment and genetic counseling, and affect obstetrical outcomes.

scholarly journals Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huili Xue ◽  
Aili Yu ◽  
Na Lin ◽  
Xuemei Chen ◽  
Min Lin ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Snp Array ◽  
Copy Number Variations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Group I ◽  
Number Variation ◽  
Fetal Ventriculomegaly ◽  
Cns Anomalies

AbstractEtiopathogenesis of fetal ventriculomegaly is poorly understood. Associations between fetal isolated ventriculomegaly and copy number variations (CNVs) have been previously described. We investigated the correlations between fetal ventriculomegaly—with or without other ultrasound anomalies—and chromosome abnormalities. 222 fetuses were divided into four groups: (I) 103 (46.4%) cases with isolated ventriculomegaly, (II) 41 (18.5%) cases accompanied by soft markers, (III) 33 (14.9%) cases complicated with central nervous system (CNS) anomalies, and (IV) 45 (20.3%) cases with accompanying anomalies. Karyotyping and single nucleotide polymorphism (SNP) array were used in parallel. Karyotype abnormalities were identified in 15/222 (6.8%) cases. Karyotype abnormalities in group I, II, III, and IV were 4/103 (3.9%), 2/41 (4.9%), 4/33 (12.1%), and 5/45 (11.1%), respectively. Concerning the SNP array analysis results, 31/222 (14.0%) were CNVs, CNVs in groups I, II, III, and IV were 11/103 (10.7%), 6/41 (14.6%), 9/33 (27.3%), and 5/45 fetuses (11.1%), respectively. Detections of clinical significant CNVs were higher in non-isolated ventriculomegaly than in isolated ventriculomegaly (16.81% vs 10.7%, P = 0.19). SNP arrays can effectively identify CNVs in fetuses with ventriculomegaly and increase the abnormal chromosomal detection rate by approximately 7.2%, especially ventriculomegaly accompanied by CNS anomalies.

scholarly journals Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation

2007 ◽  
Vol 81 (4) ◽  
pp. 768-779 ◽  
Author(s):  
Janine Wagenstaller ◽  
Stephanie Spranger ◽  
Bettina Lorenz-Depiereux ◽  
Bernd Kazmierczak ◽  
Michaela Nathrath ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Mental Retardation ◽  
Copy Number ◽  
Copy Number Variations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Oligonucleotide Arrays

Detection of Copy Number Variations in Breast Cancer Samples Using Single-nucleotide Polymorphism-targeted Massively Multiplexed PCR

2014 ◽  
Vol 207 (6) ◽  
pp. 287
Author(s):  
Joshua E. Babiarz ◽  
Bernhard G. Zimmermann ◽  
Tudor Constantin ◽  
Ryan Swenerton ◽  
Eser Kirkizlar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Copy Number Variations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Multiplexed Pcr

Identification of copy number variations in three Chinese horse breeds using 70K single nucleotide polymorphism BeadChip array

2016 ◽  
Vol 47 (5) ◽  
pp. 560-569 ◽  
Author(s):  
Adiljan Kader ◽  
Xuexue Liu ◽  
Kunzhe Dong ◽  
Shen Song ◽  
Jianfei Pan ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Copy Number Variations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

scholarly journals Chromosomal Microarray Analysis of Fetuses with Nasal Bone Anomaly

2020 ◽  
Author(s):  
Xiaorui Xie ◽  
Xiaoqing Wu ◽  
Linjuan Su ◽  
Meiying Cai ◽  
Ying Li ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Nasal Bone ◽  
Chromosomal Microarray Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Fetal Nasal Bone ◽  
Structural Abnormalities

Abstract Objective: To explore the significance and value of fetal nasal bone anomaly (absence or hypoplasia) as indications of prenatal diagnosis.Methods: A total of 102 fetuses diagnosed with nasal bone absence or hypoplasia by ultrasonography underwent chorionic, amniotic, or umbilical cord blood puncture. Single nucleotide polymorphism microarray (SNP-array) was used to analyze fetal chromosomes.Results: Of the 102 fetuses with nasal bone absence or hypoplasia, 25 (24.5%) had chromosomal abnormalities, including 15 cases of trisomy 21, one trisomy 18 case, and 9 cases of other copy number variations. Among the 52 cases with isolated nasal bone absence or hypoplasia, 7(13.5%) had chromosomal abnormalities. In 50 cases, abnormal nasal bone with additional soft markers or structural abnormalities was observed, while 18 cases (36.0%) had chromosomal abnormalities, which were significantly higher than that among the fetuses with isolated nasal bone abnormality.Conclusion: Fetal nasal bone absence or hypoplasia can be used as an indication for prenatal diagnosis. The detection rate of chromosomal abnormalities increases with additional soft markers or structural abnormalities. This study demonstrates that fetal nasal bone absence or hypoplasia is associated with micro-deletions or micro-duplications of chromosomes. Application of single nucleotide polymorphism microarray (SNP-array) technology can reduce the rate of missed prenatal diagnoses.

P–558 SNP array versus karyotype for prenatal diagnosis in fetuses with abnormal ultrasound: a systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
V Kamath ◽  
M P Chacko ◽  
M Mariano ◽  
R Kirubakaran ◽  
M S Kamath
Keyword(s):  
Systematic Review ◽  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Diagnostic Accuracy ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Index Test ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Abstract Study question Does Single nucleotide polymorphism (SNP) array provide a diagnostic advantage over conventional karyotype in prenatal diagnosis for fetuses with an abnormal ultrasound? Summary answer SNP array in the prenatal setting provides an incremental diagnostic yield over karyotype and the diagnostic accuracy is comparable with combined SNP array and karyotype What is known already Single nucleotide polymorphism and comparative genomic hybridization based arrays (aCGH) are the two chromosomal microarray (CMA) platforms available. Guidelines which recommend offering CMA instead of karyotyping for prenatal diagnosis are mainly based on studies that compared aCGH with karyotype. There is a paucity of reviews that critically appraise the role of SNP array as a prenatal diagnostic tool. We decided to estimate the incremental yield of SNP array over karyotype in detecting chromosomal abnormalities, and to determine the diagnostic accuracy of SNP alone compared with SNP array and karyotype in combination for prenatal diagnosis in fetuses with an abnormal ultrasound. Study design, size, duration We conducted a systematic review of studies comparing SNP array with karyotype for prenatal diagnosis in fetuses with an abnormal ultrasound. We performed a literature search in the electronic databases of EMBASE, PubMed, CENTRAL, CDSR, SCOPUS and Web of science for relevant studies published in the English language between January1996 and May 2020. We also hand searched the referenced list of included studies and performed a google search for grey literature to identify potential studies. Participants/materials, setting, methods The study population was women undergoing prenatal diagnosis for abnormal fetal ultrasound. Studies in which SNP array and karyotyping had been used in fetuses with abnormal ultrasound and which allowed for a 2 x 2 data extraction table were included. We estimated the incremental yields for SNP array over karyotype. For determining the diagnostic accuracy, we considered SNP array alone as the index test and combined karyotype & SNP array as the reference standard. Main results and the role of chance We included six studies for quantitative analysis. After pooling results, incremental yield of SNP array over normal karyotype was 10% (95% confidence interval, CI 4 to 16%) in fetuses with abnormal ultrasound while incremental yield of karyotype over SNP array was 1% (95% CI 0 to 2%). The agreement between SNP array and karyotype was 92%. Variant of uncertain significance (VUS) rates ranged from 4–8%. For SNP array alone versus combined SNP array and conventional karyotype, pooled sensitivity and specificity was 0.96 (95% CI 0.91 to 0.99) and 1.00 (95% CI 0.99 to 1.00) respectively. The Area under curve (AUC) was 0.99 indicating the discriminating ability of the SNP array was very high to identify the fetus with chromosomal abnormalities. Limitations, reasons for caution Only studies published in English were included. There was some degree of heterogeneity in inclusion criteria for the included studies. Wider implications of the findings: The current study suggests SNP array alone can replace conventional karyotype for prenatal diagnosis in fetus with an abnormal ultrasound. Limitations to adoption of SNP testing might include the requirement of requisite expertise to interpret the results and counsel patients appropriately, especially with the propensity of SNPs to identify VUS. Trial registration number Not applicable

scholarly journals Evaluation of chromosomal abnormalities and copy number variations in fetuses with ultrasonic soft markers

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Meiying Cai ◽  
Na Lin ◽  
Xuemei Chen ◽  
Meimei Fu ◽  
Nan Guo ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Copy Number Variations ◽  
Clinical Value ◽  
Single Nucleotide ◽  
Genetic Abnormalities ◽  
Significant Difference ◽  
Snp Array Analysis ◽  
Soft Marker

Abstract Background Some ultrasonic soft markers can be found during ultrasound examination. However, the etiology of the fetuses with ultrasonic soft markers is still unknown. This study aimed to evaluate the genetic etiology and clinical value of chromosomal abnormalities and copy number variations (CNVs) in fetuses with ultrasonic soft markers. Methods Among 1131 fetuses, 729 had single ultrasonic soft marker, 322 had two ultrasonic soft markers, and 80 had three or more ultrasonic soft markers. All fetuses underwent conventional karyotyping, followed by single nucleotide polymorphism (SNP) array analysis. Results Among 1131 fetuses with ultrasonic soft markers, 46 had chromosomal abnormalities. In addition to the 46 fetuses with chromosomal abnormalities consistent with the results of the karyotyping analysis, the SNP array identified additional 6.1% (69/1131) abnormal CNVs. The rate of abnormal CNVs in fetuses with ultrasonic soft marker, two ultrasonic soft markers, three or more ultrasonic soft markers were 6.2%, 6.2%, and 5.0%, respectively. No significant difference was found in the rate of abnormal CNVs among the groups. Conclusions Genetic abnormalities affect obstetrical outcomes. The SNP array can fully complement conventional karyotyping in fetuses with ultrasonic soft markers, improve detection rate of chromosomal abnormalities, and affect pregnancy outcomes.

scholarly journals Cytogenomic Changes in Sporadic Colorectal Cancer and Surrounding Nonneoplastic Tissues: The Relevance of Subtelomeric Copy Number Variations

2021 ◽  
Author(s):  
Mariana Rocha ◽  
Evelin Aline Zanardo ◽  
Alexandre Torchio Dias ◽  
Fabrícia Andréia Rosa Madia ◽  
Thaís Virgínia Moura Machado Costa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Copy Number ◽  
Copy Number Variations ◽  
Sporadic Colorectal Cancer ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pathogenic Cnvs ◽  
Mechanism Of Carcinogenesis ◽  
Tumor Genome ◽  
Dependent Probe

Abstract The purpose of this study was to investigate the relevance of subtelomeric cytogenomic changes in patients with sporadic colorectal cancer (CRC) using multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphism arrays. The results revealed pathogenic genomic alterations in the TNFRS18 (1p), CHL1 (3p), TRIML2 (4q), FBXO25 (8p), NKX3-1 (8p), RECQL4 (8q), DOCK8 (9p), ZMYND11 (10p), KDM5A (12p), PSPC1 (13q), ADPRTL2 (14q), MTA1 (14q), DECR2 (16p), GAS8 (16q), THOC1 (18p), CTDP1 (18q), SOX12 (20p), ADRM1 (20q), UCKL1 (20q), OPRL1 (20q), IL17RA (22q), and SYBL1 (Xq) genes. We detected copy number variations (CNVs) with frequencies greater than 40% in the probes located in 20q, which contains very important genes in the study of tumors. These findings showed instability in the tumor genome and altered regions associated with cell migration, transcription activation, apoptosis, and immune system deregulation. Unexpectedly, we detected concomitant pathogenic CNVs in tumors and surrounding tissues. Our data suggest that characterizing the genomic CRC profile is an important contribution to better understanding instability as a mechanism of carcinogenesis in CRC patients.

Genome-Wide Detection of Copy Number Variation and Identification of Genes Associated with Risk of Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4047-4047
Author(s):  
Il-Kwon Lee ◽  
Nan Young Kim ◽  
Hee Nam Kim ◽  
Yeo-Kyeoung Kim ◽  
Je-Jung Lee ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Single Nucleotide Polymorphism ◽  
Chromosomal Aberrations ◽  
Copy Number ◽  
Snp Array ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Synonymous Snps ◽  
Genome Wide ◽  
Resolution Single

Abstract Abstract 4047 Background: Despite increasing efforts to characterize the role of copy number variants (CNVs) in MM, the genetic contribution to multiple myleoma (MM) has not been fully elucidated. Recent studies showed that chromosomal aberrations are detectable in MM and can be associated with susceptibility to MM. To gain insight into the incidence of the chromosomal aberrations in MM, we examined Korean MM genomes using high-resolution single-nucleotide polymorphism (SNP) array-based analysis. Patients and Methods: As part of a larger cohort study, 14 cases analyzed had been diagnosed with MM (9 male, 5 female). Median age at diagnosis was 58 years (range, 40≂f74). Of these patients, five patients had Ig Kappa type, five with IgG Lambda, two with light chain Kappa and two with light chain Lambda. 1,140,419 CNV markers were considered on these samples using Illumina HumanOmni1-Quad v1 BeadChip. Genome-wide CNV, genotyping of markers including 32119 non-synonymous SNPs, loss of heterozygosity (LOH) analyses were performed using the GenomeStudio v2010.1. Linkage disequilibrium was analyzed by Haploview 4.2. The gene set enrichment analysis was performed using GO software, Panther. Results: The average call rates were 99.9 %. The average number of CNVs per genome in this study (353.9) is much higher than that of CNVs called in the recent studies using lower-resolution SNP- or CNV arrays. The median size of CNVs was 1,902 (range 39 ≂f 2,263,901 bp). When we analyzed the number of CNVs per genome, there was no significant difference between MM patients of different subgroups. Interestingly copy number losses were 36.7 times more frequent than copy number gains. We defined CNV regions (CNVRs) by merging overlapping CNVs (30% of overlap threshold) detected in two or more genomes. In total 1271 CNVRs identified. When all CNVRs identified in the study were compared with the CNVRs in the DGV, 149 common (more than 2 incidences) CNVRs were novel, not found in DGV database. Like CNVs, CNVRs-losses were more frequent than CNVR-gains. Defined CNVRs encompassing 29.2Mb accounted for ≂f1% of the human genome. Total of 1029 NM numbered transcripts were located near or within the 1271 CNVRs. Through gene ontology (GO) analysis, putative target genes within the commonly gained or deleted region were categorized. Gene functions significantly enriched in the identified CNVRs include receptors for signal transduction pathways, transcription factors with nucleic acid binding proteins, defense/immunity molecules and regulatory molecule related functions involved in developmental processes. Hierarchical clustering of pooled datasets clearly distinguished IgG Kappa from Lambda subtypes. Genotype distributions for 32,110 non-synonymous SNPs in MM were also examined and compared to two lab-specific as well as 90 Korean HapMap samples as control reference. Conclusions: Power of High-resolution single-nucleotide polymorphism (SNP) array-based analysis allowed us a high incidence of gains and losses in MM patients. Many of those detectable legions were previously unidentified cryptic chromosomal aberrations. Although results reveals high degrees of heterogeneity in the genomic alterations detectable in MM, genes of the signal transduction pathway and defense/immunity processes were the most frequently altered targets whose deregulation may play a role in the pathogenesis of MM. CNVs/CNVRs identified in the study will be solid resources for investigating chromosomal aberrations in MM and its potential association with MM. Disclosures: No relevant conflicts of interest to declare.

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