scholarly journals Cytogenomic Evaluation of Subjects with Syndromic and Nonsyndromic Conotruncal Heart Defects

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Karen Regina de Souza ◽  
Rafaella Mergener ◽  
Janaina Huber ◽  
Lucia Campos Pellanda ◽  
Mariluce Riegel
Keyword(s):  
Array Cgh ◽  
Heart Defects ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Data Sets ◽  
Comparative Genomic Hybridization Array ◽  
Genomic Databases ◽  
Genomic Imbalances ◽  
Genome Wide ◽  
Line Test

Despite considerable advances in the detection of genomic abnormalities in congenital heart disease (CHD), the etiology of CHD remains largely unknown. CHD is the most common birth defect and is a major cause of infant morbidity and mortality, and conotruncal defects constitute 20% of all CHD cases. We used array comparative genomic hybridization (array-CGH) to retrospectively study 60 subjects with conotruncal defects and identify genomic imbalances. The DNA copy number variations (CNVs) detected were matched with data from genomic databases, and their clinical significance was evaluated. We found that 38.3% (23/60) of CHD cases possessed genomic imbalances. In 8.3% (5/60) of these cases, the imbalances were causal or potentially causal CNVs; in 8.3% (5/60), unclassified CNVs were identified; and in 21.6% (13/60), common variants were detected. Although the interpretation of the results must be refined and there is not yet a consensus regarding the types of CHD cases in which array-CGH should be used as a first-line test, the identification of these CNVs can assist in the evaluation and management of CHD. The results of such studies emphasize the growing importance of the use of genome-wide assays in subjects with CHD to increase the number of genomic data sets associated with this condition.

scholarly journals Genomic imbalances detected through array CGH in fetuses with holoprosencephaly

2011 ◽  
Vol 69 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Isabela Nelly Machado ◽  
Juliana Karina Heinrich ◽  
Ricardo Barini
Keyword(s):  
Copy Number ◽  
Array Cgh ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Molecular Technique ◽  
Whole Genome ◽  
Genomic Imbalances ◽  
Whole Genome Microarray ◽  
Gains And Losses

OBJECTIVE: Holoprosencephaly (HPE) is heterogeneous in pathogenesis, integrating genetic susceptibility with the influence of environmental factors. Submicroscopic aberrations may contribute to the etiology of HPE. Our aim was to report the molecular analysis of 4 fetuses with HPE and normal metaphase karyotype. METHOD: A whole genome BAC-array based Comparative Genomic Hybridization (array CGH) was carried out in fetal blood samples. All potential cytogenetic alterations detected on the arrays were matched against the known copy number variations databases. RESULTS: The array CGH analysis showed copy number gains and losses in all cases. We found a recurrent deletion in 15q14 (clone RP11-23J11) and in 15q22 (clone RP11-537k8) in 2 out 4 cases analyzed. We also observed submicroscopic gain in 6p21 in 3 out of 4 fetuses in nearby clones. All these regions were tested in known databases and no copy number variations have been described for them. CONCLUSION: This is the first report of molecular characterization through a whole genome microarray CGH of fetuses with HPE. Our results may contribute to verify the effectiveness and applicability of the molecular technique of array CGH for prenatal diagnosis purposes, and contributing to the knowledge of the submicroscopic genomic instability characterization of HPE fetuses.

scholarly journals Array-based comparative genomic hybridization (ARRAY-CGH) in analysis of chromosomalaberrations and CNV in blighted ovum pregnancies

2013 ◽  
Vol 62 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Igor Nikolayevich Lebedev ◽  
Anna Aleksandrovna Kashevarova ◽  
Nikolay Alekseyevich Skryabin ◽  
Tatyana Vladimirovna Nikitina ◽  
Mariya Yevgenyevna Lopatkina ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Copy Number ◽  
Array Cgh ◽  
Copy Number Variations ◽  
Molecular Karyotyping ◽  
Comparative Genomic ◽  
Comparative Genomic Hybridization Array ◽  
Molecular Cytogenetic ◽  
Clinical Cytogenetics ◽  
Blighted Ovum

Application of modern molecular cytogenetic technologies in research and clinical practice provides unprecedented possibilities for high resolution molecular karyotyping in different areas of clinical cytogenetics. In this study the oligonucleotide-based array-CGH data about unbalanced chromosomal aberrations and copy number variations (CNV) in blighted ovum pregnancies are presented. Analysis of genes content of involved chromosomal regions was done. Scopes, perspectives and limitations of aCGH application into analysis of early pregnancy losses are discussed.

High-resolution genome-wide array-CGH reveals copy number variations associated with premature ovarian failure

Placenta ◽  
2011 ◽  
Vol 32 ◽  
pp. S282
Author(s):  
Paola Scaruffi ◽  
Sara Stigliani ◽  
Annamaria Jane Nicoletti ◽  
Pier Luigi Venturini ◽  
Gian Paolo Tonini ◽  
...  
Keyword(s):  
High Resolution ◽  
Premature Ovarian Failure ◽  
Copy Number ◽  
Array Cgh ◽  
Copy Number Variations ◽  
Ovarian Failure ◽  
Genome Wide

scholarly journals Analysis of Array-CGH Data Using the R and Bioconductor Software Suite

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Winfried A. Hofmann ◽  
Anja Weigmann ◽  
Marcel Tauscher ◽  
Britta Skawran ◽  
Tim Focken ◽  
...  
Keyword(s):  
Array Cgh ◽  
Molecular Genetic ◽  
Comparative Genomic ◽  
Accurate Identification ◽  
Genome Wide ◽  
Versatile Tool ◽  
Breakpoint Detection ◽  
Dna Copy Number Alterations ◽  
User Friendly

Background. Array-based comparative genomic hybridization (array-CGH) is an emerging high-resolution and high-throughput molecular genetic technique that allows genome-wide screening for chromosome alterations. DNA copy number alterations (CNAs) are a hallmark of somatic mutations in tumor genomes and congenital abnormalities that lead to diseases such as mental retardation. However, accurate identification of amplified or deleted regions requires a sequence of different computational analysis steps of the microarray data.Results. We have developed a user-friendly and versatile tool for the normalization, visualization, breakpoint detection, and comparative analysis of array-CGH data which allows the accurate and sensitive detection of CNAs.Conclusion. The implemented option for the determination of minimal altered regions (MARs) from a series of tumor samples is a step forward in the identification of new tumor suppressor genes or oncogenes.

scholarly journals Characteristics of Highly Polymorphic Segmental Copy-Number Variations Observed in Japanese by BAC-Array-CGH

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Norio Takahashi ◽  
Yasunari Satoh ◽  
Keiko Sasaki ◽  
Yuko Shimoichi ◽  
Keiko Sugita ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Copy Number ◽  
Array Cgh ◽  
Artificial Chromosome ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Bac Clones ◽  
Japanese Cohort ◽  
The Individual ◽  
Chromosome Microarray

Segmental copy-number variations (CNVs) may contribute to genetic variation in humans. Reports of the existence and characteristics of CNVs in a large Japanese cohort are quite limited. We report the data from a large Japanese population. We conducted population screening for 213 unrelated Japanese individuals using comparative genomic hybridization based on a bacterial artificial chromosome microarray (BAC-aCGH). We summarize the data by focusing on highly polymorphic CNVs in ≥5.0% of the individual, since they may be informative for demonstrating the relationships between genotypes and their phenotypes. We found a total of 680 CNVs at 16 different BAC-regions in the genome. The majority of the polymorphic CNVs presented on BAC-clones that overlapped with regions of segmental duplication, and the majority of the polymorphic CNVs observed in this population had been previously reported in other publications. Some of the CNVs contained genes which might be related to phenotypic heterogeneity among individuals.

scholarly journals Prenatal Diagnosis by Array Comparative Genomic Hybridization in Fetuses with Cardiac Abnormalities

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 2021
Author(s):  
Katarzyna Kowalczyk ◽  
Magdalena Bartnik-Głaska ◽  
Marta Smyk ◽  
Izabela Plaskota ◽  
Joanna Bernaciak ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Comparative Genomic Hybridization ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Array Cgh ◽  
Heart Diseases ◽  
Heart Defects ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Fetal Ultrasound

Congenital heart defects (CHDs) appear in 8–10 out of 1000 live born newborns and are one of the most common causes of deaths. In fetuses, the congenital heart defects are found even 3–5 times more often. Currently, microarray comparative genomic hybridization (array CGH) is recommended by worldwide scientific organizations as a first-line test in the prenatal diagnosis of fetuses with sonographic abnormalities, especially cardiac defects. We present the results of the application of array CGH in 484 cases with prenatally diagnosed congenital heart diseases by fetal ultrasound scanning (256 isolated CHD and 228 CHD coexisting with other malformations). We identified pathogenic aberrations and likely pathogenic genetic loci for CHD in 165 fetuses and 9 copy number variants (CNVs) of unknown clinical significance. Prenatal array-CGH is a useful method allowing the identification of all unbalanced aberrations (number and structure) with a much higher resolution than the currently applied traditional assessment techniques karyotype. Due to this ability, we identified the etiology of heart defects in 37% of cases.

scholarly journals Identification of Copy Number Variation by Array-CGH in Portuguese Children and Adolescents Diagnosed with Autism Spectrum Disorders

2019 ◽  
Vol 50 (06) ◽  
pp. 367-377
Author(s):  
S. Monteiro ◽  
J. Pinto ◽  
A. Mira Coelho ◽  
M. Leão ◽  
S. Dória
Keyword(s):  
Autism Spectrum Disorders ◽  
Copy Number ◽  
Array Cgh ◽  
Chromosomal Abnormalities ◽  
Daily Practice ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Uncertain Significance ◽  
Spectrum Disorders

Background Autism spectrum disorders (ASD) affect many children with an estimated prevalence of 1%. Array-comparative genomic hybridization (CGH) offers significant sensitivity for the identification of submicroscopic chromosomal abnormalities and it is one of the most used techniques in daily practice. The main objective of this study was to describe the usefulness of array-CGH in the etiologic diagnosis of ASD. Methods Two-hundred fifty-three patients admitted to a neurogenetic outpatient clinic and diagnosed with ASD were selected for array-CGH (4 × 180K microarrays). Public databases were used for classification in accordance with the American College of Medical Genetics Standards and Guidelines. Results About 3.56% (9/253) of copy number variations (CNVs) were classified as pathogenic. When likely pathogenic CNVs were considered, the rate increased to 11.46% (29/253). Some CNVs apparently not correlated to the ASD were also found. Considering a phenotype–genotype correlation, the patients were divided in two groups. One group according to previous literature includes all the CNVs related to ASDs (23 CNVs present in 22 children) and another with those apparently not related to ASD (10 CNVs present in 7 children). In 18 patients, a next-generation sequencing (NGS) panel were performed. From these, one pathogenic and 16 uncertain significance variants were identified. Conclusion The results of our study are in accordance with the literature, highlighting the relevance of array-CGH in the genetic of diagnosis of ASD population, namely when associated with other features. Our study also reinforces the need for complementarity between array-CGH and NGS panels or whole exome sequencing in the etiological diagnosis of ASD.

Disclosure of Copy Number Alterations in AML with Normal Karyotype Using Matrix-Based Comparative Genomic Hybridization.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 759-759
Author(s):  
Frank G. Rucker ◽  
Lars Bullinger ◽  
Hans A. Kestler ◽  
Peter Lichter ◽  
Konstanze Dohner ◽  
...  
Keyword(s):  
Molecular Markers ◽  
High Resolution ◽  
Comparative Genomic Hybridization ◽  
Copy Number ◽  
Normal Karyotype ◽  
Comparative Genomic ◽  
Copy Number Alterations ◽  
Genomic Hybridization ◽  
Genomic Imbalances ◽  
Genome Wide

Abstract Clonal chromosome abnormalities represent one of the most important prognostic factors in adult acute myeloid leukemia (AML), and cytogenetic data are used for risk-adapted treatment strategies. By conventional cytogenetic analysis, approximately 50% of patients lack clonal chromosome aberrations, and normal cytogenetics are associated with an intermediate clinical outcome. This clinically heterogeneous group seems to be in part characterized by molecular markers, such as MLL, FLT3, CEBPA, and NPM1 mutations. In order to identify novel candidate regions of genomic imbalances, we applied comparative genomic hybridization to microarrays (matrix-CGH). Using this high-resolution genome-wide screening approach we analyzed 49 normal karyotype AML cases characterized for the most common clinically relevant molecular markers (MLL-PTD n=13, FLT3-ITD n=7, FLT3-ITD/NPM1+ n=4, MLL-PTD/FLT3-ITD n=3, CEBPA+ n=12, CEBPA+/FLT3-ITD n=1; CEBPA+/NPM1+ n=1; no molecular markers n=8) with a microarray platform consisting of 2799 different BAC or PAC clones. A set of 1500 of these clones covers the whole human genome with a physical distance of approximately 2 Mb. The remaining 1299 clones either contiguously span genomic regions known to be frequently involved in hematologic malignancies (e.g., 1p, 2p, 3q, 7q, 9p, 11q, 12q, 13q, 17p, 18q) (n=600) or contain oncogenes or tumor suppressor genes (n=699). In addition to known copy number polymorphisms in 5q11, 7q22, 7q35, 14q32, and 15q11, the CLuster Along Chromosomes method (CLAC; http://www-stat.stanford.edu/~wp57/CGH-Miner) disclosed copy number alterations (CNAs) in terms of gains in 1p, 11q, 12q, and 17p. CNAs in terms of losses were identified in 9p, 11q, 12p, 12q, and 13q. Two-class supervised analyses using the significance analysis of microarrays (SAM) method identified for the MLL-PTD cases a gain of a single clone harboring the MLL gene. While the significance of these findings, which are currently validated using fluorescence in-situ hybridization (FISH), still remains to be determined, our preliminary results already demonstrate the power and reliablity of this microarray-based technique allowing genome-wide screens of genomic imbalances as the MLL aberration was detected in all cases known to have a MLL-PTD. Furthermore, ongoing correlation of high-resolution genomic profiling with global gene expression studies will help to disclose pathways underlying normal karyotype AML, thereby leading to new insights of leukemogenesis.

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