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

Abstract

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.

MCDA twins with discordant malformations: submicroscopic chromosomal anomalies detected by chromosomal microarray analysis and clinical outcomes

“…Only one in six MZ twin pairs with discordant CHD was detected with three copy number differences in Breckpot et al 's study . On the contrary, Castellani et al . identified CNVs and genes that were previously implicated in mental abnormalities in four of the six twin pairs with discordant schizophrenia.…”

“…In a word, we have no adequacy evidence to conclude that CNV gain at 2q13 of the four cases in our study is pathogenic. Postnatal studies that reported the different distribution of CNVs in discordant MZ twins are involved in many types of diseases, including CHD, 6 urorectal malformations, 7 schizophrenia, 5 Parkinson disease, 24 congenital diaphragmatic hernia, esophageal atresia, 25 attention problems 26 and so on. The reported conclusions were contradictory.…”

“…Copy number variants (CNVs) lead to deletions and duplications of a given segment of the genome. Castellani et al . revealed likely candidate genes and CNVs for the discordance of four of the six MZ twin pairs for Schizophrenia.…”

“…4 Copy number variants (CNVs) lead to deletions and duplications of a given segment of the genome. Castellani et al 5 revealed likely candidate genes and CNVs for the discordance of four of the six MZ twin pairs for Schizophrenia. Breckpot et al 6 recently identified disease-causing de novo CNVs in one affected twin out of six MZ twin pairs discordant for congenital heart defects.…”

Integrating Genomic Correlation Structure Improves Copy Number Variations Detection

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Copy number variants (CNVs) refers to gains or losses of the DNA segments in comparison to a reference genome. CNVs have garnered extensive interests in recent years as they play an important role susceptibility to disorders and diseases such as autism, schizophrenia and cancer [1][2][3][4][5][6][7]. Although innovation in modern technology is promoting the discoveries related to CNVs, the methodology for CNV detection is still lagging, which limits the novel discoveries regarding the role of CNVs in complex diseases.

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