CNV Workshop: an integrated platform for high-throughput copy number variation discovery and clinical diagnostics

High-throughput sequencing based on copy number variation (CNV-seq) is commonly used to detect chromosomal abnormalities. This study identifies chromosomal abnormalities in aborted embryos/fetuses in early and middle pregnancy and explores the application value of CNV-seq in determining the causes of pregnancy termination. High-throughput sequencing was used to detect chromosome copy number variations (CNVs) in 116 aborted embryos in early and middle pregnancy. The detection data were compared with the Database of Genomic Variants (DGV), the Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER), and the Online Mendelian Inheritance in Man (OMIM) database to determine the CNV type and the clinical significance. High-throughput sequencing results were successfully obtained in 109 out of 116 specimens, with a detection success rate of 93.97%. In brief, there were 64 cases with abnormal chromosome numbers and 23 cases with CNVs, in which 10 were pathogenic mutations and 13 were variants of uncertain significance. An abnormal chromosome number is the most important reason for embryo termination in early and middle pregnancy, followed by pathogenic chromosome CNVs. CNV-seq can quickly and accurately detect chromosome abnormalities and identify microdeletion and microduplication CNVs that cannot be detected by conventional chromosome analysis, which is convenient and efficient for genetic etiology diagnosis in miscarriage.

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Accurate and reliable high-throughput detection of copy number variation in the human genome

Genome Research ◽

10.1101/gr.5630906 ◽

2006 ◽

Vol 16 (12) ◽

pp. 1566-1574 ◽

Cited By ~ 111

Author(s):

H. Fiegler ◽

R. Redon ◽

D. Andrews ◽

C. Scott ◽

R. Andrews ◽

...

Keyword(s):

Copy Number Variation ◽

Human Genome ◽

High Throughput ◽

Copy Number ◽

Number Variation ◽

High Throughput Detection

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Use of high-throughput targeted exome-sequencing to screen for copy number variation in hypertrophic cardiomyopathy

European Journal of Medical Genetics ◽

10.1016/j.ejmg.2015.10.001 ◽

2015 ◽

Vol 58 (11) ◽

pp. 611-616 ◽

Cited By ~ 21

Author(s):

L.R. Lopes ◽

C. Murphy ◽

P. Syrris ◽

C. Dalageorgou ◽

W.J. McKenna ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Copy Number Variation ◽

Exome Sequencing ◽

High Throughput ◽

Copy Number ◽

Targeted Exome Sequencing ◽

Number Variation

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The clinical context of copy number variation in the human genome

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399410001390 ◽

2010 ◽

Vol 12 ◽

Cited By ~ 119

Author(s):

Charles Lee ◽

Stephen W. Scherer

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Clinical Diagnostics ◽

Genomic Variation ◽

Single Nucleotide ◽

Genomic Changes ◽

Creative Solutions ◽

Number Variation ◽

The Relationship ◽

Prevalent Form

During the past five years, copy number variation (CNV) has emerged as a highly prevalent form of genomic variation, bridging the interval between long-recognised microscopic chromosomal alterations and single-nucleotide changes. These genomic segmental differences among humans reflect the dynamic nature of genomes, and account for both normal variations among us and variations that predispose to conditions of medical consequence. Here, we place CNVs into their historical and medical contexts, focusing on how these variations can be recognised, documented, characterised and interpreted in clinical diagnostics. We also discuss how they can cause disease or influence adaptation to an environment. Various clinical exemplars are drawn out to illustrate salient characteristics and residual enigmas of CNVs, particularly the complexity of the data and information associated with CNVs relative to that of single-nucleotide variation. The potential is immense for CNVs to explain and predict disorders and traits that have long resisted understanding. However, creative solutions are needed to manage the sudden and overwhelming burden of expectation for laboratories and clinicians to assay and interpret these complex genomic variations as awareness permeates medical practice. Challenges remain for understanding the relationship between genomic changes and the phenotypes that might be predicted and prevented by such knowledge.

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High-Throughput Sequencing and Copy Number Variation Detection Using Formalin Fixed Embedded Tissue in Metastatic Gastric Cancer

PLoS ONE ◽

10.1371/journal.pone.0111693 ◽

2014 ◽

Vol 9 (11) ◽

pp. e111693 ◽

Cited By ~ 29

Author(s):

Seokhwi Kim ◽

Jeeyun Lee ◽

Min Eui Hong ◽

In-Gu Do ◽

So Young Kang ◽

...

Keyword(s):

Gastric Cancer ◽

Copy Number Variation ◽

High Throughput ◽

Copy Number ◽

High Throughput Sequencing ◽

Metastatic Gastric Cancer ◽

Number Variation ◽

Copy Number Variation Detection ◽

Formalin Fixed

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Assessment of algorithms for high throughput detection of genomic copy number variation in oligonucleotide microarray data

BMC Bioinformatics ◽

10.1186/1471-2105-8-368 ◽

2007 ◽

Vol 8 (1) ◽

pp. 368 ◽

Cited By ~ 34

Author(s):

Ágnes Baross ◽

Allen D Delaney ◽

H Irene Li ◽

Tarun Nayar ◽

Stephane Flibotte ◽

...

Keyword(s):

Copy Number Variation ◽

High Throughput ◽

Microarray Data ◽

Copy Number ◽

Oligonucleotide Microarray ◽

Genomic Copy Number ◽

Genomic Copy ◽

Number Variation ◽

High Throughput Detection ◽

Genomic Copy Number Variation

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MONTAGE: a new tool for high-throughput detection of mosaic copy number variation

BMC Genomics ◽

10.1186/s12864-021-07395-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Joseph T. Glessner ◽

Xiao Chang ◽

Yichuan Liu ◽

Jin Li ◽

Munir Khan ◽

...

Keyword(s):

Copy Number Variation ◽

High Throughput ◽

Copy Number ◽

Copy Number Variants ◽

Cell Types ◽

Disease Phenotype ◽

Multiple Phenotypes ◽

Genome Wide ◽

Number Variation ◽

The Impact

Abstract Background Not all cells in a given individual are identical in their genomic makeup. Mosaicism describes such a phenomenon where a mixture of genotypic states in certain genomic segments exists within the same individual. Mosaicism is a prevalent and impactful class of non-integer state copy number variation (CNV). Mosaicism implies that certain cell types or subset of cells contain a CNV in a segment of the genome while other cells in the same individual do not. Several studies have investigated the impact of mosaicism in single patients or small cohorts but no comprehensive scan of mosaic CNVs has been undertaken to accurately detect such variants and interpret their impact on human health and disease. Results We developed a tool called Montage to improve the accuracy of detection of mosaic copy number variants in a high throughput fashion. Montage directly interfaces with ParseCNV2 algorithm to establish disease phenotype genome-wide association and determine which genomic ranges had more or less than expected frequency of mosaic events. We screened for mosaic events in over 350,000 samples using 1% allele frequency as the detection limit. Additionally, we uncovered disease associations of multiple phenotypes with mosaic CNVs at several genomic loci. We additionally investigated the allele imbalance observations genome-wide to define non-diploid and non-integer copy number states. Conclusions Our novel algorithm presents an efficient tool with fast computational runtime and high levels of accuracy of mosaic CNV detection. A curated mosaic CNV callset of 3716 events in 2269 samples is presented with comparability to previous reports and disease phenotype associations. The new algorithm can be freely accessed via: https://github.com/CAG-CNV/MONTAGE.

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A Survey of Copy‐Number Variation Detection Tools Based on High‐Throughput Sequencing Data

Current Protocols in Human Genetics ◽

10.1002/0471142905.hg0719s75 ◽

2012 ◽

Vol 75 (1) ◽

Cited By ~ 12

Author(s):

Ruibin Xi ◽

Semin Lee ◽

Peter J. Park

Keyword(s):

Copy Number Variation ◽

High Throughput ◽

Copy Number ◽

High Throughput Sequencing ◽

Sequencing Data ◽

High Throughput Sequencing Data ◽

Number Variation ◽

Copy Number Variation Detection

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Clinical diagnosis of single-gene disorders and chromosomal abnormalities based on BGISEQ-500 platform

10.1101/675991 ◽

2019 ◽

Author(s):

Yanqiu Liu ◽

Liangwei Mao ◽

Xiaoming Wei ◽

Jianfen Man ◽

Wenqian Zhang ◽

...

Keyword(s):

Copy Number Variation ◽

Clinical Diagnosis ◽

High Throughput ◽

Copy Number ◽

Chromosomal Abnormalities ◽

Genomic Copy Number ◽

Genomic Copy ◽

Monogenic Diseases ◽

Number Variation ◽

Genomic Copy Number Variation

AbstractMost of the variation in the human genome is a single nucleotide variation (SNV) based on a single base or small fragment insertions and deletions and genomic copy number variation (CNV). Both types of mutations are involved in many human diseases. Such diseases often have complex clinical symptoms and difficult clinical diagnosis, so an effective detection method is needed to help clinical diagnosis and prevent birth defects. With the development of sequencing technology, the method of chip capture combined with high-throughput sequencing has been extensively used because of its high throughput, high accuracy, high speed and low cost. This study designed a chip that captures the coding region of 3043 genes associated with 4013 monogenic diseases. In addition, 148 chromosomal abnormalities can be identified by setting targets in specific regions. Compared with the whole exon chip, the chip can detect 4013 monogenic diseases and 148 chromosomal abnormalities at a lower cost, including SNV, intra-gene CNV and genomic copy number variation. This study utilized a strategy of combining the BGISEQ500 sequencing platform with the chip to identify 102 disease-associated mutations in 63 patients, 69 of which were new mutations. The evaluation test results also show that this combination complies with the requirements of clinical testing and has good clinical application value.

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