Genetic factors inherited from both diploid parents interact to affect genome stability and fertility in resynthesized allotetraploid B. napus

Abstract The genetic diversity in Brassica napus (canola, rapeseed) is limited because of few hybridization events and selection for important oil quality traits. One possible means of overcoming this challenge is through resynthesizing B. napus hybrids by crossing the diploid parents in order to broaden its gene pool. However, resynthesized B. napus lines are often unstable and infertile, unlike B. napus cultivars. Meiotic stability in established B. napus may have arisen through allele inheritance from the progenitor species. We tested this hypothesis by characterizing 41 resynthesized B. napus lines produced by crosses between eight B. rapa and eight B. oleracea lines for copy number variation resulting from non-homologous recombination events, allele inheritance, and fertility. We resequenced eight B. rapa and five B. oleracea parent accessions, and analyzed the allelic variation in a list of meiosis gene homologs. SNP genotyping was performed using the Illumina Infinium Brassica 60K array for three individuals per line. Self-pollinated seed-set and genome stability (number of copy number variants) were significantly affected by the interaction between both B. rapa and B. oleracea parental genotypes. We identified two putative meiosis gene candidates ( HEI10 and MCM8 ) which were significantly associated with meiosis and/or fertility as well as genome stability. Our results support the hypothesis that allelic variants inherited from parental genotypes affect genome stability and fertility in resynthesized rapeseed.

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

Frontiers in Genetics ◽

10.3389/fgene.2021.731355 ◽

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.

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The Role of Copy Number Variation in Psychiatric Disorders

Psychiatric Genetics ◽

10.1093/med/9780190221973.003.0006 ◽

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.

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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17249253 ◽

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.

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Genetics of Schizophrenia and Bipolar Disorder

10.1093/med/9780190681425.003.0013 ◽

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

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Copy number variation of LINGO1 in familial dystonic tremor

Neurology Genetics ◽

10.1212/nxg.0000000000000307 ◽

2019 ◽

Vol 5 (1) ◽

pp. e307 ◽

Cited By ~ 4

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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Association of copy number variation in the AHI1 gene with risk of obesity in the Chinese population

Acta Endocrinologica ◽

10.1530/eje-11-0999 ◽

2012 ◽

Vol 166 (4) ◽

pp. 727-734 ◽

Cited By ~ 11

Author(s):

Liansha Huang ◽

Dacai Teng ◽

Hao Wang ◽

Guoqing Sheng ◽

Tonghua Liu

Keyword(s):

Copy Number ◽

Integration Site ◽

Linear Trend ◽

Copy Number Variants ◽

Gene Copy Number ◽

Copy Number Gain ◽

Gene Copy ◽

Significant Linear Trend ◽

Number Variation ◽

Dna Copy Number Change

ObjectiveThe prevalence of obesity has increased dramatically over the past decade. Gene copy number variants (CNVs) have been recognized as a hereditable source of susceptibility in human complex diseases including obesity. Recent studies have shown that Abelson helper integration site 1 (Ahi1) gene has a significant contribution in the homeostasis regulation in mouse models of obesity. A study was therefore carried out to investigate whether CNVs inAHI1gene contribute to human obesity.Subjects and methodsWe analyzed samples from 70 Chinese overweight adults and 74 healthy controls for DNA copy number change using the Affymetrix single-nucleotide polymorphism (SNP) 6.0 array. Validation of CNVs ofAHI1was achieved by real-time PCR using the ΔΔCtmethod.ResultsCopy number gain analysis revealed significant gains (P=0.0017) ofAHI1gene copy number in 17 of 70 (24.3%) samples but only four of 74 (5.4%) controls overall. Then we studied the frequency distribution of CNVs inAHI1gene according to body mass index (BMI) grade. Five out of 28 (18.5%) at-risk obese, six out of 26 (26.9%) moderate obese, and six out of 17 (29.4%) severe obese subjects studied showed increasedAHI1gene copy number.ConclusionsThe result suggested that there was a significant linear trend for increasingAHI1gene copy number frequencies with increasing BMI.

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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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Copy Number Variation: Methods and Clinical Applications

Applied Sciences ◽

10.3390/app11020819 ◽

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.

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Genetics of Schizophrenia and Bipolar Disorder

Neurobiology of Mental Illness ◽

10.1093/med/9780199934959.003.0018 ◽

2013 ◽

pp. 232-246 ◽

Cited By ~ 1

Author(s):

Pamela Sklar

Keyword(s):

Bipolar Disorder ◽

Copy Number ◽

Psychotic Disorders ◽

De Novo ◽

Copy Number Variants ◽

Nucleotide Polymorphisms ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Sequencing Studies ◽

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. The explosion of strong and convincing genetic evidence 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. There is a role for rare single nucleotide variation as well as de novo genetic variation being pointed to in new sequencing studies, but their overall contribution to risk is less clear. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, there is evidence for polygenicity and as yet no deep sequencing surveys have been published. Several intriguing biological pathways are suggested by these genetic findings related to microRNAs and calcium channel signaling. 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. Translating these results into biological and etiological understanding has not yet advanced, and will likely only do so when experimental methods are developed than can address the large numbers of genes and variants within them that, along with environmental and stochastic effects, result in the development of disease for a particular person.

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Copy Number Variation Distribution in Six Monozygotic Twin Pairs Discordant for Schizophrenia

Twin Research and Human Genetics ◽

10.1017/thg.2014.6 ◽

2014 ◽

Vol 17 (2) ◽

pp. 108-120 ◽

Cited By ~ 21

Author(s):

Christina A. Castellani ◽

Zain Awamleh ◽

Melkaye G. Melka ◽

Richard L. O'Reilly ◽

Shiva M. Singh

Keyword(s):

Copy Number ◽

De Novo ◽

Twin Pair ◽

Neurodevelopmental Disorder ◽

Copy Number Variants ◽

Monozygotic Twins ◽

Monozygotic Twin ◽

Chain Reaction ◽

Number Variation ◽

Polymerase Chain

We have evaluated copy number variants (CNVs) in six monozygotic twin pairs discordant for schizophrenia. The data from Affymetrix® Human SNP 6.0 arrays™ were analyzed using Affymetrix® Genotyping Console™, Partek® Genomics Suite™, PennCNV, and Golden Helix SVS™. This yielded both program-specific and overlapping results. Only CNVs called by Affymetrix Genotyping Console, Partek Genomics Suite, and PennCNV were used in further analysis. This analysis included an assessment of calls in each of the six twin pairs towards identification of unique CNVs in affected and unaffected co-twins. Real time polymerase chain reaction (PCR) experiments confirmed one CNV loss at 7q11.21 that was found in the affected patient but not in the unaffected twin. The results identified CNVs and genes that were previously implicated in mental abnormalities in four of the six twin pairs. It included PYY (twin pairs 1 and 5), EPHA3 (twin pair 3), KIAA1211L (twin pair 4), and GPR139 (twin pair 5). They represent likely candidate genes and CNVs for the discordance of four of the six monozygotic twin pairs for this heterogeneous neurodevelopmental disorder. An explanation for these differences is ontogenetic de novo events that differentiate in the monozygotic twins during development.

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