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 Copy number variation analysis of twin pairs discordant for cleft lip with or without cleft palate

2019 ◽  
Vol 33 ◽  
pp. 205873841985587
Author(s):  
Luca Scapoli ◽  
Francesco Carinci ◽  
Annalisa Palmieri ◽  
Francesca Cura ◽  
Alessandro Baj ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Copy Number ◽  
Large Scale ◽  
Cleft Lip ◽  
Small Sample Size ◽  
Copy Number Variants ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Small Sample ◽  
High Level

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.

Genetics of Schizophrenia and Bipolar Disorder

2013 ◽  
pp. 232-246 ◽  
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.

scholarly journals De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes

2019 ◽  
Vol 27 (7) ◽  
pp. 1121-1133 ◽  
Author(s):  
Nirmal Vadgama ◽  
Alan Pittman ◽  
Michael Simpson ◽  
Niranjanan Nirmalananthan ◽  
Robin Murray ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
De Novo ◽  
Monozygotic Twins ◽  
Single Nucleotide ◽  
Number Variation ◽  
Disease Related Genes

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.

scholarly journals Association of mitochondrial copy number variation and T16189C polymorphism with colorectal cancer in North Indian population

Tumor Biology ◽  
2017 ◽  
Vol 39 (11) ◽  
pp. 101042831774029 ◽  
Author(s):  
Bhupender Kumar ◽  
Zafar Iqbal Bhat ◽  
Savita Bansal ◽  
Sunil Saini ◽  
Afreen Naseem ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Copy Number Variation ◽  
Odds Ratio ◽  
Copy Number ◽  
Indian Population ◽  
Chain Reaction ◽  
Mitochondrial Copy Number ◽  
Number Variation ◽  
Polymerase Chain ◽  
Colorectal Cancer Patients

Globally, colorectal cancer is the third most common type of cancer. Genetic instability leading to cancer development is one of the major causes for development of cancer. Alterations in mitochondrial genome, that is, mutations, single-nucleotide polymorphisms, and copy number variations are known to contribute in cancer development. The aim of our study was to investigate association of mitochondrial T16189C polymorphism and copy number variation with colorectal cancer in North Indian population. DNA isolated from peripheral blood of 126 colorectal cancer patients and 114 healthy North Indian subjects was analyzed for T16189C polymorphism and half of them for mitochondrial copy number variation. Genotyping was done using polymerase chain reaction–restriction fragment length polymorphism, and copy number variation was estimated using real-time polymerase chain reaction, numbers of mitochondrial copies and found to be significantly higher in colorectal cancer patients than healthy controls (88 (58–154), p = 0.001). In the regression analysis, increased mitochondrial copy number variation was associated with risk of colorectal cancer (odds ratio = 2.885, 95% confidence interval = 1.3–6.358). However, T16189C polymorphism was found to be significantly associated with the risk of rectal cancer (odds ratio = 5.213, p = 0.001) and non-significantly with colon cancer (odds ratio = 0.867, p = 0.791). Also, false-positive report probability analysis was done to validate the significant findings. Our results here indicate that mitochondrial copy number variation may be playing an important role in the development of colorectal cancer, and detection of mitochondrial copy number variation can be used as a biomarker for predicting the risk of colorectal cancer in North Indian subjects.

Sign in / Sign up

Export Citation Format

Share Document