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

Copyright © The Author(s) 2018 Hundreds 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 tho...

Full description

Bibliographic Details
Main Authors: Stamouli, S., Anderlid, B., Willfors, C., Thiruvahindrapuram, B., Wei, J., Berggren, S., Nordgren, A., Scherer, S., Lichtenstein, P., Tammimies, K., Bolte, Sven
Format: Journal Article
Published: Cambridge University Press 2018
Online Access:http://hdl.handle.net/20.500.11937/66412
_version_ 1848761315349233664
author Stamouli, S.
Anderlid, B.
Willfors, C.
Thiruvahindrapuram, B.
Wei, J.
Berggren, S.
Nordgren, A.
Scherer, S.
Lichtenstein, P.
Tammimies, K.
Bolte, Sven
author_facet Stamouli, S.
Anderlid, B.
Willfors, C.
Thiruvahindrapuram, B.
Wei, J.
Berggren, S.
Nordgren, A.
Scherer, S.
Lichtenstein, P.
Tammimies, K.
Bolte, Sven
author_sort Stamouli, S.
building Curtin Institutional Repository
collection Online Access
description Copyright © The Author(s) 2018 Hundreds 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. We sought to investigate the contribution of rare CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on postzygotic CNVs in MZ pairs discordant for autism spectrum disorder (ASD) using the Illumina Infinium PsychArray. In our sample, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. We did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system, such as a rare deletion affecting HNRNPU, in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p = .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 suggests that the discordance of NDDs in our sample of twins is not explained by discordant CNVs. 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.
first_indexed 2025-11-14T10:29:43Z
format Journal Article
id curtin-20.500.11937-66412
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T10:29:43Z
publishDate 2018
publisher Cambridge University Press
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-664122018-04-30T02:48:45Z Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders Stamouli, S. Anderlid, B. Willfors, C. Thiruvahindrapuram, B. Wei, J. Berggren, S. Nordgren, A. Scherer, S. Lichtenstein, P. Tammimies, K. Bolte, Sven Copyright © The Author(s) 2018 Hundreds 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. We sought to investigate the contribution of rare CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on postzygotic CNVs in MZ pairs discordant for autism spectrum disorder (ASD) using the Illumina Infinium PsychArray. In our sample, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. We did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system, such as a rare deletion affecting HNRNPU, in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p = .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 suggests that the discordance of NDDs in our sample of twins is not explained by discordant CNVs. 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/66412 10.1017/thg.2017.69 Cambridge University Press restricted
spellingShingle Stamouli, S.
Anderlid, B.
Willfors, C.
Thiruvahindrapuram, B.
Wei, J.
Berggren, S.
Nordgren, A.
Scherer, S.
Lichtenstein, P.
Tammimies, K.
Bolte, Sven
Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
title Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
title_full Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
title_fullStr Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
title_full_unstemmed Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
title_short Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
title_sort copy number variation analysis of 100 twin pairs enriched for neurodevelopmental disorders
url http://hdl.handle.net/20.500.11937/66412