Use of single nucleotide polymorphism (SNP) array karyotyping to detect clonal chromosomal abnormalities in myelodysplastic syndrome (MDS) and refractory anemia with ringed sideroblasts (RARS)

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.

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Chromosomal Microarray Analysis of Fetuses with Nasal Bone Anomaly

10.21203/rs.3.rs-28412/v1 ◽

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.

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

Human Reproduction ◽

10.1093/humrep/deab130.557 ◽

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

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Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes

Blood ◽

10.1182/blood-2007-03-079673 ◽

2007 ◽

Vol 110 (9) ◽

pp. 3365-3373 ◽

Cited By ~ 150

Author(s):

Azim Mohamedali ◽

Joop Gäken ◽

Natalie A. Twine ◽

Wendy Ingram ◽

Nigel Westwood ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Prognostic Significance ◽

Low Risk ◽

Refractory Anemia ◽

Polymorphism Analysis ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Ringed Sideroblasts ◽

Multilineage Dysplasia ◽

Normal Cytogenetics

Abstract Low-risk myelodysplastic syndrome (MDS) with normal cytogenetics accounts for approximately 50% of MDS patients. There are no pathognomonic markers in these cases and the diagnosis rests on cytomorphologic abnormalities in bone marrow and/or peripheral blood. Affymetrix high-resolution single-nucleotide polymorphism (SNP) genotyping microarrays allow detection of cytogenetically cryptic genomic aberrations. We have studied 119 low-risk MDS patients (refractory anemia [RA] = 22; refractory cytopenia with multilineage dysplasia [RCMD] = 51; refractory anemia with ringed sideroblasts [RARS] = 12; refractory cytopenia with multilineage dysplasia with ringed sideroblasts [RCMD-RS] = 12; 5q− syndrome = 16; refractory anemia with excess blasts [RAEB] = 6) using SNP microarrays to seek chromosomal markers undetected by conventional cytogenetics. Loss of heterozygosity (LOH) detected by 50K arrays was verified using 250K and 500K arrays. We demonstrate the presence of uniparental disomy (UPD) in 46%, deletions in 10%, and amplifications in 8% of cases. Copy number (CN) changes were acquired, whereas UPDs were also detected in constitutional DNA. UPD on 4q was identified in 25% of RARS, 12% of RCMD with normal cytogenetics, 17% of RAEB, and 6% of 5q− syndrome cases. Univariate analysis showed deletions (P = .04) and International Prognostic Scoring System (IPSS; P < .001) scores correlated with overall survival; however, on multivariate analysis only IPSS scores retained prognostic significance (P < .001). We show, for the first time, that SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions.

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Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome

Journal of Clinical Pathology ◽

10.1136/jclinpath-2016-204023 ◽

2016 ◽

Vol 70 (5) ◽

pp. 435-442 ◽

Cited By ~ 12

Author(s):

Fernanda Borges da Silva ◽

João Agostinho Machado-Neto ◽

Virginia Helena Leira Lipoli Bertini ◽

Elvira Deolinda Rodrigues Pereira Velloso ◽

Cristina Alonso Ratis ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Myelodysplastic Syndrome ◽

Chromosomal Abnormalities ◽

Single Nucleotide Polymorphism Array ◽

Nucleotide Polymorphism ◽

Single Nucleotide

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

Molecular Cytogenetics ◽

10.1186/s13039-021-00537-2 ◽

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.

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SNP array analysis in hematologic malignancies: avoiding false discoveries

Blood ◽

10.1182/blood-2009-11-203182 ◽

2010 ◽

Vol 115 (21) ◽

pp. 4157-4161 ◽

Cited By ~ 64

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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