scholarly journals Classifying and Evaluating Fetuses With Ventriculomegaly in Genetic Etiologic Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Meiying Cai ◽  
Hailong Huang ◽  
Liangpu Xu ◽  
Na Lin
Keyword(s):  
Statistical Significance ◽  
Snp Array ◽  
Copy Number Variations ◽  
Good Prognosis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Prenatal Consultation ◽  
Pathogenic Cnvs ◽  
Abnormal Copy Number

The association between genetics and fetuses with ventriculomegaly (VM) is unknown. This study aimed to classify and evaluate abnormal copy number variations (CNVs) in fetuses with VM. From December 2016 to September 2020, amniotic fluid or umbilical cord blood from 293 pregnant women carrying fetuses with VM was extracted for single-nucleotide polymorphism microarray (SNP array). Among 293 fetuses with VM, 31 were detected with abnormal CNVs, including 22 with pathogenic CNVs (7.51%) and nine with variation of uncertain clinical significance (VUS) CNVs (3.07%). Of the 22 fetuses with pathogenic CNVs, 13 had known disease syndromes. Among the 293 fetuses, 133 had mild isolated VM [pathogenic CNVs, 7/133 (5.26%)]; 142 had mild non-isolated VM [pathogenic CNVs, 13/142 (9.15%)]; 12 had severe isolated VM [pathogenic CNVs, 2/12 (16.67%)]; and six had severe non-isolated VM (no abnormal CNVs was detected). There was no statistical significance in the rate of pathogenic CNVs among the four groups (P = 0.326, P > 0.05). Among the 267 fetuses with successful follow-up, 38 were terminated (of these, 21 had pathogenic CNVs). Of the 229 fetuses, two had developmental delay and the remaining 227 had a good prognosis after birth. Overall, the results are useful for the detection of fetal microdeletion/microduplication syndrome and for the accurate assessment of fetal prognosis in prenatal consultation.

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 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.

scholarly journals Advantages of Single Nucleotide Polymorphism(SNP)Array Based Karyotyping in Detection of Chromosomal Defects Combined with Metaphase Cytogenetics in Myelodysplastic Syndromes (MDS)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5424-5424
Author(s):  
Yang Ou ◽  
Hongbin Yu ◽  
Yu Wu
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Conflicts Of Interest ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Copy Number Variations ◽  
Genomic Alteration ◽  
Specific Situation ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Chromosomal Defects

Background: Metaphase cytogenetics (MC), which has an important diagnostic, prognostic and therapeutic roles in myelodysplastic syndrome (MDS), is widely used as cytogenetic analyzing tools. It can present entire cytogenetic information at one time, although with some limitations such as Hypocellularity, fewer mitotic cells, secondary myelofibrosis and technicians' subjectivity. Single nucleotide polymorphism(SNP)array based karyotyping ( SNP-A based karyotyping) is a novel diagnostic tool which can detect copy number variations with a high resolution. More importantly, SNP-based array has a unique advantage in detection of loss of heterozygosity, also referred as to uniparental disomy (UPD), which results from duplication of a paternal (unimaternal) or maternal (unipaternal) chromosomal region and concurrent loss of the other allele. However the technology is still relatively expensive, and balanced structural METHOD: We analyzed SNP-A results from 127 patients diagnosed of MDS or MDS related myeloid malignancies(including 6 MDS/MPN, 11 acute myeloid leukemia from MDS, and 110 MDS). 122 patients of them had both MC and SNP-A results. We compared the frequency and diagnostic sensitivity between the cytogenetic aberration findings by MC and genomic alteration findings by SNP-A. In addition, we investigated the novel or additional lesions detected by SNP-A which had not been found by MC, and find further information about the edges of SNP-A. We drew attention to the missing matters of SNP-A which mentioned in MC reports to integrate the limits of SNP-A. We also used multiple-factor analysis to find out the specific situation which MC are not inferior to SNP-A. RESULTS: There are 199 genomic alteration findings in 127 patients by SNP-A ( including 43 UPDs, 57 gain alterations, 86 loss alterations and 13 complicated alterations). The average length of genomic alterations found by SNP-A is 27795.71Kb, the longest one is GainMosaic(1) (248375kb), the shortest is a UPD found in 17q (41.88Kb). In the 122 patients who had both MC and SNP-A results, SNP-A turns to be more effective than MC in significant chromosomal defects(58.2% vs 36.9%,P<0.005). Novel or additional lesions are detected by SNP-A in patients with normal/noninformative (42.2%) and abnormal(44.4%) MC results. By comparison of the specific results between SNP-A and MC, we found in all 10 complex karyotypes (not less than three cytogenetic aberrations detected by MC), SNP-A could be a more sensitive method to gain more information about particular lesions. Except 10 complex karyotypes, 78 novel or additional lesions in 40 patients could be detected by SNP-A while won't turn up in Metaphase cytogenetics, and these included 38 aberrations of UPD and 33 mosaic deletions or gains. 6 chromosome translocations was detected by MC while not found by SNP-A because of no changes in copy numbers. Two mark DNAs were found in two different patients by MC while SNP-A were negative and need further examination. And combined MC/SNP-A lead to higher diagnostic yield of chromosomal defects, compared MC alone(61.4% vs 37.5%, P<0.005). CONCLUSIONS: SNP-A based karyotyping seemed to be more sensitive than MC. Because SNP-A based karyotyping have a high throughput to find mosaic deletions or gains and it is the unique metod to detect UPD. SNP-A also can show more information than MC in complex karyotypes. Disclosures No relevant conflicts of interest to declare.

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 The role of single nucleotide polymorphism of val66met (rs6265) of the brain-derived neurotropic factor in formation of endpoints after st-segment elevation myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
O.V Petyunina ◽  
M.P Kopytsya ◽  
A.E Berezin ◽  
A.A Berezin
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Bdnf Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
St Segment Elevation ◽  
Acute Stemi ◽  
End Point ◽  
St Segment ◽  
The Brain

Abstract Background The single nucleotide polymorphism (SNP) Val66Met (rs6265) of the brain-derived neurotrophic factor (BDNF) gene is a possible candidate that is associated with the development of psychopathology and combines it with cardiovascular events. Purpose To research the possible associations of single-nucleotide polymorphism of Val66Met BDNF gene with the occurrence of endpoints after 6 months of follow-up after ST segment elevation myocardial infarction (STEMI). Methods 256 acute STEMI patients after successful primary percutaneous coronary intervention (PCI) were enrolled in the study. TIMI III blood flow restoring through culprit artery was determined. The study of SNP of Val66Met (rs6265) of the BDNF gene was performed by real-time polymerase chain reaction. The emotional state of the patients and its relationship with stress were assessed with the questionnaire “Depression, Anxiety and Stress-21”. All acute STEMI patients received adjuvant treatment due to current ESC recommendations. All procedures performed in the study involving human participants were in accordance with the ethical standards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and approved by the local ethics committee. Written inform consent was obtained from each patient. The primary endpoint was combined event (follow-up major adverse cardiac events – MACEs and hospitalization) that occurred within 6-month of the discharge from the hospital. MACEs were defined as the composite of CV death, recurrent angina, newly diagnosed heart failure. Results The frequency of genotypes Val66Met gene for BDNF in STEMI patients (n=256) was the following: 66ValVal=74.2% (n=190), 66ValMet + 66MetMet – 25.8% (n=66). The 66ValMet + 66MetMet polymorphism in the BDNF gene, stress and anxiety on 10–14 days before the event, as well as reduced left ventricular ejection fraction (LVEF), were independently associated with combined 6 months clinical end point after STEMI. Severity of depression according to depression scale was more profound in individuals with 66ValMet+66MetMet polymorphysms in BDNF gene (P=0.045) than in patients with 66ValVal genotype. Univariate and multivariate linear regressions has shown that 66ValMet+66MetMet genotype in BDNF gene, anxiety and stress before event, LVEF had independent power on dependent variable entitled combined end point after 6 month observation for STEMI patients with successful revascularization (P=0.0395). Kaplan-Meier curves demonstrated that STEMI patients with 66ValVal genotype in BDNF gene had a lower accumulation of combined end point compared with acute STEMI patients with 66ValMet+66ValMet polymorphism (Cox-criterion, P=0.019; log-rang criterion, P=0.03). Conclusion The Val66Met polymorphism in BDNF gene was found as an independent predictor for combined 6-month clinical end points after acute STEMI treated primary PCI. Funding Acknowledgement Type of funding source: None

scholarly journals Prenatal diagnosis of 7 cases with uniparental disomy by utilization of single nucleotide polymorphism array

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lili Zhou ◽  
Zhaoke Zheng ◽  
Yunzhi Xu ◽  
Xiaoxiao Lv ◽  
Chenyang Xu ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Molecular Analysis ◽  
Correct Diagnosis ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Chromosome 1 ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Rescue Mechanism

Abstract Background The phenotypes of uniparental disomy (UPD) are variable, which may either have no clinical impact, lead to clinical signs and symptoms. Molecular analysis is essential for making a correct diagnosis. This study involved a retrospective analysis of 4512 prenatal diagnosis samples and explored the molecular characteristics and prenatal phenotypes of UPD using a single nucleotide polymorphism (SNP) array. Results Out of the 4512 samples, a total of seven cases of UPD were detected with an overall frequency of 0.16%. Among the seven cases of UPD, two cases are associated with chromosomal aberrations (2/7), four cases (4/7) had abnormal ultrasonographic findings. One case presented with iso-UPD (14), and two case presented with mixed hetero/iso-UPD (15), which were confirmed by Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as maternal UPD (15) associated with Prader-Willi syndrome (PWS). Four cases had iso-UPD for chromosome 1, 3, 14, and 16, respectively; this is consistent with the monosomy rescue mechanism. Another three cases presented with mixed hetero/isodisomy were consistent with a trisomy rescue mechanism. Conclusion The prenatal phenotypes of UPD are variable and molecular analysis is essential for making a correct diagnosis and genetic counselling of UPD. The SNP array is a useful genetic test in prenatal diagnosis cases with UPD.

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

scholarly journals SNP array analysis in hematologic malignancies: avoiding false discoveries

Blood ◽  
2010 ◽  
Vol 115 (21) ◽  
pp. 4157-4161 ◽  
Author(s):  
Stefan Heinrichs ◽  
Cheng Li ◽  
A. Thomas Look
Keyword(s):  
Single Nucleotide Polymorphism ◽  
High Resolution ◽  
Snp Array ◽  
Hematologic Malignancies ◽  
Cancer Genome ◽  
Patient Specific ◽  
Nucleotide Polymorphism ◽  
Array Analysis ◽  
Single Nucleotide ◽  
Therapeutic Decisions

Comprehensive analysis of the cancer genome has become a standard approach to identifying new disease loci, and ultimately will guide therapeutic decisions. A key technology in this effort, single nucleotide polymorphism arrays, has been applied in hematologic malignancies to detect deletions, amplifications, and loss of heterozygosity (LOH) at high resolution. An inherent challenge of such studies lies in correctly distinguishing somatically acquired, cancer-specific lesions from patient-specific inherited copy number variations or segments of homozygosity. Failure to include appropriate normal DNA reference samples for each patient in retrospective or prospective studies makes it difficult to identify small somatic deletions not evident by standard cytogenetic analysis. In addition, the lack of proper controls can also lead to vastly overestimated frequencies of LOH without accompanying loss of DNA copies, so-called copy-neutral LOH. Here we use examples from patients with myeloid malignancies to demonstrate the superiority of matched tumor and normal DNA samples (paired studies) over multiple unpaired samples with respect to reducing false discovery rates in high-resolution single nucleotide polymorphism array analysis. Comparisons between matched tumor and normal samples will continue to be critical as the field moves from high resolution array analysis to deep sequencing to detect abnormalities in the cancer genome.

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