scholarly journals Copy-Number Variations Observed in a Japanese Population by BAC Array CGH: Summary of Relatively Rare CNVs

2012 ◽  
Vol 2012 ◽  
pp. 1-10
Author(s):  
Yasunari Satoh ◽  
Keiko Sasaki ◽  
Yuko Shimoichi ◽  
Keiko Sugita ◽  
Hiroaki Katayama ◽  
...  
Keyword(s):  
Copy Number ◽  
Rare Variants ◽  
Artificial Chromosome ◽  
Copy Number Variations ◽  
Unrelated Individual ◽  
Comparative Genomic ◽  
Common Disease ◽  
Rare Cnvs ◽  
Japanese Cohort ◽  
Study Population

Copy-number variations (CNVs) may contribute to genetic variation in humans. Reports regarding existence and characteristics of CNVs in a large apparently healthy Japanese cohort are quite limited. We report the data from a screening of 213 unrelated Japanese individuals using comparative genomic hybridization based on a bacterial artificial chromosome microarray (BAC aCGH). In a previous paper, we summarized the data by focusing on highly polymorphic CNVs (in ≥5.0 % of the individuals). However, rare variations have recently received attention from scientists who espouse a hypothesis called “common disease and rare variants.” Here, we report CNVs identified in fewer than 10 individuals in our study population. We found a total of 126 CNVs at 52 different BAC regions in the genome. The CNVs observed at 27 of the 52 BAC-regions were found in only one unrelated individual. The majority of CNVs found in this study were not identified in the Japanese who were examined in the other studies. Family studies were conducted, and the results demonstrated that the CNVs were inherited from one parent in the families.

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 “Abnormal vertebral patterns in genetically heterogeneous deceased fetuses and neonates: evidence of selection against variations”

2019 ◽  
Author(s):  
Pauline C. Schut ◽  
Erwin Brosens ◽  
Frietson Galis ◽  
Clara M. A. Ten Broek ◽  
Inge M.M. Baijens ◽  
...  
Keyword(s):  
Copy Number ◽  
Single Nucleotide Polymorphism Array ◽  
Copy Number Variations ◽  
Cervical Region ◽  
Nucleotide Polymorphism ◽  
Rare Cnvs ◽  
Single Nucleotide ◽  
Neonatal Deaths ◽  
Coding Regions ◽  
Cervical Ribs

AbstractObjectiveTo assess the vertebral pattern in a cohort of deceased fetuses and neonates, and to study the possible impact of DNA Copy Number Variations (CNVs) in coding regions and/or disturbing enhancers on the development of the vertebral pattern.MethodRadiographs of 445 fetuses and infants, deceased between 2009 and 2015, were assessed. Terminations of pregnancies, stillbirths and neonatal deaths were included. Patients were excluded if the vertebral pattern could not be determined. Copy number profiles of 265 patients were determined using single nucleotide polymorphism array.Results274/374 patients (73.3%) had an abnormal vertebral pattern. Cervical ribs were present in 188/374 (50.3%) and were significantly more common in stillbirths (69/128 (53.9%)) and terminations of pregnancies (101/188 (53.7%)), compared to live births (18/58, 31.0%, p = 0.006). None of the rare CNVs were recurrent or overlapped candidate genes for vertebral patterning.ConclusionThe presence of an abnormal vertebral pattern, particularly in the cervical region, could be a sign of disruption at critical, highly interactive and conserved stages of embryogenesis. The vertebral pattern might provide valuable information regarding fetal and neonatal outcome. CNV analyses did not identify a mutual genetic cause for the occurrence of vertebral patterning abnormalities, indicating genetic heterogeneity.

scholarly journals Multiplex ligation-dependent probe amplification – a short overview

2020 ◽  
Vol 28 (2) ◽  
pp. 123-131
Author(s):  
Valeriu Moldovan ◽  
Elena Moldovan
Keyword(s):  
Copy Number ◽  
Genetic Disorders ◽  
Cost Effective ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Gene Deletions ◽  
Conventional Cytogenetic Analysis ◽  
Main Technique ◽  
Cost Effective Technique ◽  
Dependent Probe

AbstractMultiplex Ligation-dependent Probe Amplification is a technique proposed for the detection of deletions or duplications that may lead to copy number variations in genomic DNA, mainly due to its higher resolution, and shorter overall diagnosis time, when compared with techniques traditionally used, namely karyotyping, fluorescence in situ hybridization, and array comparative genomic hybridization. Multiplex Ligation-dependent Probe Amplification is a fast (about 2 days), useful and cost-effective technique, being suitable for the diagnosis of hereditary conditions caused by complete or partial gene deletions or duplications, as these conditions are either more difficult or impossible to be diagnosed by other techniques, such as PCR, Real-Time PCR, or sequencing (Sanger or Next Generation). Due to its numerous advantages over conventional cytogenetic analysis techniques, Multiplex Ligation-dependent Probe Amplification could be used in the near future as the main technique for the molecular investigation of genetic conditions caused by copy number variations, in both rare and complex genetic disorders.

scholarly journals Bayesian Disease Classification Using Copy Number Data

2014 ◽  
Vol 13s2 ◽  
pp. CIN.S13785 ◽  
Author(s):  
Subharup Guha ◽  
Yuan Ji ◽  
Veerabhadran Baladandayuthapani
Keyword(s):  
Copy Number ◽  
Copy Number Variations ◽  
Disease Classification ◽  
Classification Model ◽  
Basic Knowledge ◽  
Comparative Genomic ◽  
Breast Cancer Dataset ◽  
Disease Category ◽  
Cancer Dataset ◽  
Disease States

DNA copy number variations (CNVs) have been shown to be associated with cancer development and progression. The detection of these CNVs has the potential to impact the basic knowledge and treatment of many types of cancers, and can play a role in the discovery and development of molecular-based personalized cancer therapies. One of the most common types of high-resolution chromosomal microarrays is array-based comparative genomic hybridization (aCGH) methods that assay DNA CNVs across the whole genomic landscape in a single experiment. In this article we propose methods to use aCGH profiles to predict disease states. We employ a Bayesian classification model and treat disease states as outcome, and aCGH profiles as covariates in order to identify significant regions of the genome associated with disease subclasses. We propose a principled two-stage method where we first make inferences on the underlying copy number states associated with the aCGH emissions based on hidden Markov model (HMM) formulations to account for serial dependencies in neighboring probes. Subsequently, we infer associations with disease outcomes, conditional on the copy number states, using Bayesian linear variable selection procedures. The selected probes and their effects are parameters that are useful for predicting the disease categories of any additional individuals on the basis of their aCGH profiles. Using simulated datasets, we investigate the method's accuracy in detecting disease category. Our methodology is motivated by and applied to a breast cancer dataset consisting of aCGH profiles assayed on patients from multiple disease subtypes.

scholarly journals A large data resource of genomic copy number variation across neurodevelopmental disorders

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Mehdi Zarrei ◽  
Christie L. Burton ◽  
Worrawat Engchuan ◽  
Edwin J. Young ◽  
Edward J. Higginbotham ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
Population Control ◽  
Large Data ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Genomic Disorder ◽  
Rare Cnvs ◽  
Data Resource ◽  
Compulsive Disorder

Abstract Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.

Overall Genomic Pattern Is a Predictor of Outcome in Neuroblastoma

2009 ◽  
Vol 27 (7) ◽  
pp. 1026-1033 ◽  
Author(s):  
Isabelle Janoueix-Lerosey ◽  
Gudrun Schleiermacher ◽  
Evi Michels ◽  
Véronique Mosseri ◽  
Agnès Ribeiro ◽  
...  
Keyword(s):  
Copy Number ◽  
Prognostic Significance ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Mycn Amplification ◽  
Clinical Markers ◽  
Prognostic Information ◽  
Stage 4 ◽  
Risk Of Relapse

Purpose For a comprehensive overview of the genetic alterations of neuroblastoma, their association and clinical significance, we conducted a whole-genome DNA copy number analysis. Patients and Methods A series of 493 neuroblastoma (NB) samples was investigated by array-based comparative genomic hybridization in two consecutive steps (224, then 269 patients). Results Genomic analysis identified several types of profiles. Tumors presenting exclusively whole-chromosome copy number variations were associated with excellent survival. No disease-related death was observed in this group. In contrast, tumors with any type of segmental chromosome alterations characterized patients with a high risk of relapse. Patients with both numerical and segmental abnormalities clearly shared the higher risk of relapse of segmental-only patients. In a multivariate analysis, taking into account the genomic profile, but also previously described individual genetic and clinical markers with prognostic significance, the presence of segmental alterations with (HR, 7.3; 95% CI, 3.7 to 14.5; P < .001) or without MYCN amplification (HR, 4.5; 95% CI, 2.4 to 8.4; P < .001) was the strongest predictor of relapse; the other significant variables were age older than 18 months (HR, 1.8; 95% CI, 1.2 to 2.8; P = .004) and stage 4 (HR, 1.8; 95% CI, 1.2 to 2.7; P = .005). Finally, within tumors showing segmental alterations, stage 4, age, MYCN amplification, 1p and 11q deletions, and 1q gain were independent predictors of decreased overall survival. Conclusion The analysis of the overall genomic pattern, which probably unravels particular genomic instability mechanisms rather than the analysis of individual markers, is essential to predict relapse in NB patients. It adds critical prognostic information to conventional markers and should be included in future treatment stratification.

scholarly journals Motor Chip: A Comparative Genomic Hybridization Microarray for Copy-Number Mutations in 245 Neuromuscular Disorders

2011 ◽  
Vol 57 (11) ◽  
pp. 1584-1596 ◽  
Author(s):  
Giulio Piluso ◽  
Manuela Dionisi ◽  
Francesca Del Vecchio Blanco ◽  
Annalaura Torella ◽  
Stefania Aurino ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Copy Number ◽  
Neuromuscular Disorders ◽  
Neuromuscular Diseases ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Specific Gene ◽  
Disease Genes ◽  
Genomic Hybridization ◽  
Gene Coverage

BACKGROUND Array-based comparative genomic hybridization (aCGH) is a reference high-throughput technology for detecting large pathogenic or polymorphic copy-number variations in the human genome; however, a number of quantitative monogenic mutations, such as smaller heterozygous deletions or duplications, are usually missed in most disease genes when proper multiplex ligation-dependent probe assays are not performed. METHODS We developed the Motor Chip, a customized CGH array with exonic coverage of 245 genes involved in neuromuscular disorders (NMDs), as well as 180 candidate disease genes. We analyzed DNA samples from 26 patients with known deletions or duplications in NMDs, 11 patients with partial molecular diagnoses, and 19 patients with a clinical diagnosis alone. RESULTS The Motor Chip efficiently confirmed and refined the copy-number mutations in all of the characterized patients, even when only a single exon was involved. In noncharacterized or partially characterized patients, we found deletions in the SETX (senataxin), SGCG [sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein)], and LAMA2 (laminin, alpha 2) genes, as well as duplications involving LAMA2 and the DYSF [dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)] locus. CONCLUSIONS The combination of exon-specific gene coverage and optimized platform and probe selection makes the Motor Chip a complementary tool for molecular diagnosis and gene investigation in neuromuscular diseases.

scholarly journals Array-based comparative genomic hybridization identifies a high frequency of copy number variations in patients with syndromic overgrowth

2009 ◽  
Vol 18 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Valérie Malan ◽  
Suzanne Chevallier ◽  
Gwendoline Soler ◽  
Christine Coubes ◽  
Didier Lacombe ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
High Frequency ◽  
Copy Number ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Genomic Hybridization
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