scholarly journals Large Autosomal Copy-Number Differences within Unselected Monozygotic Twin Pairs are Rare

2015 ◽  
Vol 18 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Allan F. McRae ◽  
Peter M. Visscher ◽  
Grant W. Montgomery ◽  
Nicholas G. Martin
Keyword(s):  
Copy Number ◽  
Twin Pair ◽  
Population Sample ◽  
Monozygotic Twin ◽  
Manual Annotation ◽  
Causal Gene ◽  
Number Variation ◽  
Autosomal Copy ◽  
Mz Twins ◽  
Important System

Monozygotic (MZ) twins form an important system for the study of biological plasticity in humans. While MZ twins are generally considered to be genetically identical, a number of studies have emerged that have demonstrated copy-number differences within a twin pair, particularly in those discordant for disease. The rate of autosomal copy-number variation (CNV) discordance within MZ twin pairs was investigated using a population sample of 376 twin pairs genotyped on Illumina Human610-Quad arrays. After CNV calling using both QuantiSNP and PennCNV followed by manual annotation, only a single CNV difference was observed within the MZ twin pairs, being a 130 KB duplication of chromosome 5. Five other potential discordant CNV were called by the software, but excluded based on manual annotation of the regions. It is concluded that large CNV discordance is rare within MZ twin pairs, indicating that any CNV difference found within phenotypically discordant MZ twin pairs has a high probability of containing the causal gene(s) involved.

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

2014 ◽  
Vol 17 (2) ◽  
pp. 108-120 ◽  
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.

scholarly journals Characterization of autosomal copy-number variation in African Americans: the HyperGEN Study

2011 ◽  
Vol 19 (12) ◽  
pp. 1271-1275 ◽  
Author(s):  
Nathan E Wineinger ◽  
Nicholas M Pajewski ◽  
Richard E Kennedy ◽  
Mary K Wojczynski ◽  
Laura K Vaughan ◽  
...  
Keyword(s):  
African Americans ◽  
Copy Number Variation ◽  
Copy Number ◽  
Number Variation ◽  
Autosomal Copy

scholarly journals Novel Population Specific Autosomal Copy Number Variation and Its Functional Analysis amongst Negritos from Peninsular Malaysia

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100371 ◽  
Author(s):  
Siti Shuhada Mokhtar ◽  
Christian R. Marshall ◽  
Maude E. Phipps ◽  
Bhooma Thiruvahindrapuram ◽  
Anath C. Lionel ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Copy Number Variation ◽  
Copy Number ◽  
Peninsular Malaysia ◽  
Number Variation ◽  
Autosomal Copy

scholarly journals Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders

2017 ◽  
Author(s):  
Sofia Stamouli ◽  
Britt-Marie Anderlid ◽  
Charlotte Willfors ◽  
Bhooma Thiruvahindrapuram ◽  
John Wei ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
De Novo ◽  
Single Cells ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Rare Cnvs ◽  
Number Variation ◽  
Discordant Twins ◽  
Mz Twins

AbstractHundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. Here, we sought to investigate the contribution of CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on MZ pairs discordant for autism spectrum disorder (ASD) using the PsychChip array. In our collection, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. When analyzing the burden of rare CNVs among pairs concordant and discordant for ASD/NDD in comparison with typically developed (TD) pairs, no differences were found. However, we did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p=0.02). Our results are in concordance with earlier findings that postzygotic de novo CNV events are typically rare in genomic DNA derived from saliva or blood and, in the majority of MZ twins, do not explain the discordance of NDDs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.

scholarly journals Copy number variation and neurodevelopmental problems in females and males in the general population

2017 ◽  
Author(s):  
Joanna Martin ◽  
Kristiina Tammimies ◽  
Robert Karlsson ◽  
Yi Lu ◽  
Henrik Larsson ◽  
...  
Keyword(s):  
General Population ◽  
Copy Number ◽  
Population Sample ◽  
Copy Number Variants ◽  
Rare Cnvs ◽  
Large Deletions ◽  
Number Variation ◽  
Twin Children ◽  
Anxiety Depression ◽  
Neurodevelopmental Problems

AbstractObjectiveNeurodevelopmental problems (NPs) are childhood phenotypes that are more common in males. Conversely, anxiety and depression (which are frequently comorbid with NPs) are more common in females. Rare copy number variants (CNVs) have been implicated in clinically-defined NPs. Here, we aimed to characterise the relationship between rare CNVs with NPs and anxiety/depression in a population sample of twin children. Additionally, we examined whether sex-specific CNV effects underlie the sex bias of these disorders.MethodWe analysed a sample of N=12,982 children, of whom 5.3% had narrowly-defined NPs (clinically-diagnosed), 20.9% had broadly-defined NPs (based on validated screening measures, but no diagnosis) and 3.0% had clinically-diagnosed anxiety or depression. Rare (<1% frequency) CNVs were categorised by size (medium: 100-500kb or large: >500kb), type (duplication or deletion) and putative relevance to NPs (affecting previously implicated loci or evolutionarily-constrained genes). We tested for associations between the different CNV categories with NPs and anxiety/depression, followed by examination of sex-specific effects.ResultsMedium deletions (OR(CI)=1.18(1.05-1.33),p=0.0053) and large duplications (OR(CI)=1.45(1.19-1.75),p=0.00017) were associated with broadly-defined NPs. Large deletions (OR(CI)=1.85(1.14-3.01),p=0.013) were associated with narrowly-defined NPs. The effect sizes increased for large NP-relevant CNVs (broadly-defined: OR(CI)=1.60(1.06-2.42),p=0.025; narrowly-defined: OR(CI)=3.64(2.16-6.13),p=1.2E-6). No sex differences in CNV burden were found in individuals with NPs (p>0.05). In individuals diagnosed with anxiety or depression, females were more likely to have large CNVs (OR(CI)=3.75(1.45-9.68),p=0.0064).ConclusionRare CNVs are significantly associated with both narrowly- and broadly-defined NPs in a general population sample of children. Our results also suggest that large, rare CNVs may show sex-specific phenotypic effects.

scholarly journals Dosage compensation can buffer copy-number variation in wild yeast

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
James Hose ◽  
Chris Mun Yong ◽  
Maria Sardi ◽  
Zhishi Wang ◽  
Michael A Newton ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Gene Amplification ◽  
Dosage Compensation ◽  
Copy Number ◽  
Gene Dosage ◽  
Phenotypic Evolution ◽  
Wild Populations ◽  
Causal Gene ◽  
Wild Yeast ◽  
Number Variation

Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at 10–30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations—but they show elevated rates of gene amplification, suggesting that copy-number variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution.

Identification of Novel Germline and Tumor-Specific Nucleotide Variants and Copy Number Variation in Clival Chordomas by Exome Sequencing

2015 ◽  
Vol 76 (S 01) ◽  
Author(s):  
Georgios Zenonos ◽  
Peter Howard ◽  
Maureen Lyons-Weiler ◽  
Wang Eric ◽  
William LaFambroise ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Exome Sequencing ◽  
Copy Number ◽  
Number Variation ◽  
Specific Nucleotide

The impact of paralog genes: detection of copy number variation in spinal muscle atrophy patients

BIOCELL ◽  
2018 ◽  
Vol 42 (3) ◽  
pp. 87-91 ◽  
Author(s):  
Sergio LAURITO ◽  
Juan A. CUETO ◽  
Jimena PEREZ ◽  
Mar韆 ROQU�
Keyword(s):  
Copy Number Variation ◽  
Muscle Atrophy ◽  
Copy Number ◽  
Number Variation ◽  
The Impact

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

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