scholarly journals Copy Number Variation: Methods and Clinical Applications

2021 ◽  
Vol 11 (2) ◽  
pp. 819
Author(s):  
Ondrej Pös ◽  
Jan Radvanszky ◽  
Jakub Styk ◽  
Zuzana Pös ◽  
Gergely Buglyó ◽  
...  
Keyword(s):  
Copy Number ◽  
Genetic Diseases ◽  
Copy Number Variants ◽  
Clinical Diagnostics ◽  
Whole Body ◽  
Current State ◽  
Number Variation ◽  
Detection Capabilities ◽  
Gains And Losses ◽  
Cnv Detection

Gains and losses of large segments of genomic DNA, known as copy number variants (CNVs) gained considerable interest in clinical diagnostics lately, as particular forms may lead to inherited genetic diseases. In recent decades, researchers developed a wide variety of cytogenetic and molecular methods with different detection capabilities to detect clinically relevant CNVs. In this review, we summarize methodological progress from conventional approaches to current state of the art techniques capable of detecting CNVs from a few bases up to several megabases. Although the recent rapid progress of sequencing methods has enabled precise detection of CNVs, determining their functional effect on cellular and whole-body physiology remains a challenge. Here, we provide a comprehensive list of databases and bioinformatics tools that may serve as useful assets for researchers, laboratory diagnosticians, and clinical geneticists facing the challenge of CNV detection and interpretation.

scholarly journals CNV-BAC: Copy number Variation Detection in Bacterial Circular Genome

2020 ◽  
Vol 36 (12) ◽  
pp. 3890-3891
Author(s):  
Linjie Wu ◽  
Han Wang ◽  
Yuchao Xia ◽  
Ruibin Xi
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Genome Structure ◽  
Real Data ◽  
Read Depth ◽  
Supplementary Information ◽  
Circular Genome ◽  
Number Variation ◽  
Copy Number Variation Detection ◽  
Cnv Detection

Abstract Motivation Whole-genome sequencing (WGS) is widely used for copy number variation (CNV) detection. However, for most bacteria, their circular genome structure and high replication rate make reads more enriched near the replication origin. CNV detection based on read depth could be seriously influenced by such replication bias. Results We show that the replication bias is widespread using ∼200 bacterial WGS data. We develop CNV-BAC (CNV-Bacteria) that can properly normalize the replication bias and other known biases in bacterial WGS data and can accurately detect CNVs. Simulation and real data analysis show that CNV-BAC achieves the best performance in CNV detection compared with available algorithms. Availability and implementation CNV-BAC is available at https://github.com/XiDsLab/CNV-BAC. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Detection and characterization of copy number variants based on whole-genome sequencing by DNBSEQ platforms

2019 ◽  
Author(s):  
Junhua Rao ◽  
Lihua Peng ◽  
Fang Chen ◽  
Hui Jiang ◽  
Chunyu Geng ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Copy Number Variant ◽  
Whole Genome ◽  
Genome Wide ◽  
Wide Range ◽  
Distribution Sensitivity ◽  
Cnv Detection

AbstractBackgroundNext-generation sequence (NGS) has rapidly developed in past years which makes whole-genome sequencing (WGS) becoming a more cost- and time-efficient choice in wide range of biological researches. We usually focus on some variant detection via WGS data, such as detection of single nucleotide polymorphism (SNP), insertion and deletion (Indel) and copy number variant (CNV), which playing an important role in many human diseases. However, the feasibility of CNV detection based on WGS by DNBSEQ™ platforms was unclear. We systematically analysed the genome-wide CNV detection power of DNBSEQ™ platforms and Illumina platforms on NA12878 with five commonly used tools, respectively.ResultsDNBSEQ™ platforms showed stable ability to detect slighter more CNVs on genome-wide (average 1.24-fold than Illumina platforms). Then, CNVs based on DNBSEQ™ platforms and Illumina platforms were evaluated with two public benchmarks of NA12878, respectively. DNBSEQ™ and Illumina platforms showed similar sensitivities and precisions on both two benchmarks. Further, the difference between tools for CNV detection was analyzed, and indicated the selection of tool for CNV detection could affected the CNV performance, such as count, distribution, sensitivity and precision.ConclusionThe major contribution of this paper is providing a comprehensive guide for CNV detection based on WGS by DNBSEQ™ platforms for the first time.

scholarly journals HandyCNV: Standardized Summary, Annotation, Comparison, and Visualization of Copy Number Variant, Copy Number Variation Region, and Runs of Homozygosity

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinghang Zhou ◽  
Liyuan Liu ◽  
Thomas J. Lopdell ◽  
Dorian J. Garrick ◽  
Yuangang Shi
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Copy Number Variant ◽  
R Package ◽  
Copy Number Variation Region ◽  
Runs Of Homozygosity ◽  
Number Variation ◽  
Genomic Studies ◽  
Computing Platforms ◽  
Analysis System

Detection of CNVs (copy number variants) and ROH (runs of homozygosity) from SNP (single nucleotide polymorphism) genotyping data is often required in genomic studies. The post-analysis of CNV and ROH generally involves many steps, potentially across multiple computing platforms, which requires the researchers to be familiar with many different tools. In order to get around this problem and improve research efficiency, we present an R package that integrates the summarization, annotation, map conversion, comparison and visualization functions involved in studies of CNV and ROH. This one-stop post-analysis system is standardized, comprehensive, reproducible, timesaving, and user-friendly for researchers in humans and most diploid livestock species.

scholarly journals GROM-RD: Resolving genomic biases to improve read depth detection of copy number variants

2014 ◽  
Author(s):  
Sean D Smith ◽  
Joseph K Kawash ◽  
Andrey Grigoriev
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Read Depth ◽  
Read Coverage ◽  
Novel Approach ◽  
Depth Analysis ◽  
Gc Bias ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
Cnv Detection

Amplifications or deletions of genome segments, known as copy number variants (CNVs), have been associated with many diseases. Read depth analysis of next-generation sequencing (NGS) is an essential method of detecting CNVs. However, genome read coverage is frequently distorted by various biases of NGS platforms, which reduce predictive capabilities of existing approaches. Additionally, the use of read depth tools has been somewhat hindered by imprecise breakpoint identification. We developed GROM-RD, an algorithm that analyzes multiple biases in read coverage to detect CNVs in NGS data. We found non-uniform variance across distinct GC regions after using existing GC bias correction methods and developed a novel approach to normalize such variance. Although complex and repetitive genome segments complicate CNV detection, GROM-RD adjusts for repeat bias and uses a two-pipeline masking approach to detect CNVs in complex and repetitive segments while improving sensitivity in less complicated regions. To overcome a typical weakness of RD methods, GROM-RD employs a CNV search using size-varying overlapping windows to improve breakpoint resolution. We compared our method to two widely used programs based on read depth methods, CNVnator and RDXplorer, and observed improved CNV detection and breakpoint accuracy for GROM-RD. GROM-RD is available at http://grigoriev.rutgers.edu/software/

The Role of Copy Number Variation in Psychiatric Disorders

2018 ◽  
pp. 84-95
Author(s):  
Elliott Rees ◽  
George Kirov
Keyword(s):  
Autism Spectrum Disorders ◽  
Copy Number ◽  
Selection Pressure ◽  
Copy Number Variants ◽  
Autism Spectrum ◽  
High Odds ◽  
Strong Selection ◽  
Increase Risk ◽  
Number Variation

Copy number variants (CNVs) are deletions, duplications, inversions, or translocations of large DNA segments. They can play a significant role in human disease. Thirteen CNVs have received strong statistical support for involvement in schizophrenia. They are all rare in cases (<1%), much rarer among controls, and have high odds ratios (ORs) for causing disease. The same CNVs also increase risk for autism spectrum disorders, developmental delay, and medical/physical comorbidities. The penetrance of these CNVs for any disorder is relatively high, ranging from 10% for 15q11.2 deletions to nearly 100% for deletions at 22q11.2. Strong selection pressure operates against carriers of these CNVs. Most of these are formed by non-allelic homologous recombination (NAHR), which leads to high mutation rates, thus maintaining the rates of these CNVs in the general population, despite the strong selection forces.

scholarly journals Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4–BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature

2020 ◽  
Vol 17 (24) ◽  
pp. 9253
Author(s):  
Natália Oliva-Teles ◽  
Maria Chiara de Stefano ◽  
Louise Gallagher ◽  
Severin Rakic ◽  
Paula Jorge ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
Chromosomal Region ◽  
Current Knowledge ◽  
Copy Number Variants ◽  
Inclusion Criteria ◽  
Rare Disorders ◽  
Number Variation ◽  
Malformation Syndromes ◽  
Neuropsychiatric Conditions

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4–BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers’ cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.

Genetics of Schizophrenia and Bipolar Disorder

2017 ◽  
Author(s):  
Alexander Charney ◽  
Pamela Sklar
Keyword(s):  
Bipolar Disorder ◽  
Copy Number ◽  
Psychotic Disorders ◽  
Copy Number Variants ◽  
Nucleotide Polymorphisms ◽  
Common Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Number Variation

Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. There is now convincing genetic evidence that indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, and there is evidence for polygenicity. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder.

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

2010 ◽  
Vol 11 (1) ◽  
pp. 74 ◽  
Author(s):  
Xiaowu Gai ◽  
Juan C Perin ◽  
Kevin Murphy ◽  
Ryan O'Hara ◽  
Monica D'arcy ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
High Throughput ◽  
Copy Number ◽  
Clinical Diagnostics ◽  
Integrated Platform ◽  
Number Variation

The clinical context of copy number variation in the human genome

2010 ◽  
Vol 12 ◽  
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.

scholarly journals Copy number variation of LINGO1 in familial dystonic tremor

2019 ◽  
Vol 5 (1) ◽  
pp. e307 ◽  
Author(s):  
Vafa Alakbarzade ◽  
Thomas Iype ◽  
Barry A. Chioza ◽  
Royana Singh ◽  
Gaurav V. Harlalka ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Gene Copy ◽  
Whole Genome ◽  
Snp Microarray ◽  
Dystonic Tremor ◽  
South Indian ◽  
Number Variation ◽  
Microarray Studies

ObjectiveTo elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor.MethodsWhole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals.ResultsWhole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire LINGO1 gene.ConclusionsThe identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.

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