Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development

Abstract Recurrent deletions and duplications of chromosome 7q11.23 copy number variants (CNVs) are associated with several psychiatric disorders. Although phenotypic abnormalities have been observed in patients, causal genes responsible for CNV-associated diagnoses and traits are still poorly under...

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Autores principales:	Liang Chen, Weidi Wang, Wenxiang Cai, Weichen Song, Wei Qian, Guan Ning Lin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/880c847ab3384d7fa5f731deebc2754e
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spelling	oai:doaj.org-article:880c847ab3384d7fa5f731deebc2754e2021-12-02T15:51:14ZSpatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development10.1038/s41598-021-87632-x2045-2322https://doaj.org/article/880c847ab3384d7fa5f731deebc2754e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87632-xhttps://doaj.org/toc/2045-2322Abstract Recurrent deletions and duplications of chromosome 7q11.23 copy number variants (CNVs) are associated with several psychiatric disorders. Although phenotypic abnormalities have been observed in patients, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Furthermore, the targeted human brain regions, developmental stages, protein networks, and signaling pathways, influenced by this CNV remain unclear. Previous works showed GTF2I involved in Williams-Beuren syndrome, but pathways affected by GTF2I are indistinct. We first constructed dynamic spatiotemporal networks of 7q11.23 genes by combining data from the brain developmental transcriptome with physical interactions of 7q11.23 proteins. Topological changes were observed in protein–protein interaction (PPI) networks throughout different stages of brain development. Early and late fetal periods of development in the cortex, striatum, hippocampus, and amygdale were observed as the vital periods and regions for 7q11.23 CNV proteins. CNV proteins and their partners are significantly enriched in DNA repair pathway. As a driver gene, GTF2I interacted with PRKDC and BRCA1 to involve in DNA repair pathway. The physical interaction between GTF2I with PRKDC was confirmed experimentally by the liquid chromatography-tandem mass spectrometry (LC–MS/MS). We identified that early and late fetal periods are crucial for 7q11.23 genes to affect brain development. Our results implicate that 7q11.23 CNV genes converge on the DNA repair pathway to contribute to the pathogenesis of psychiatric diseases.Liang ChenWeidi WangWenxiang CaiWeichen SongWei QianGuan Ning LinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liang Chen Weidi Wang Wenxiang Cai Weichen Song Wei Qian Guan Ning Lin Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development
description	Abstract Recurrent deletions and duplications of chromosome 7q11.23 copy number variants (CNVs) are associated with several psychiatric disorders. Although phenotypic abnormalities have been observed in patients, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Furthermore, the targeted human brain regions, developmental stages, protein networks, and signaling pathways, influenced by this CNV remain unclear. Previous works showed GTF2I involved in Williams-Beuren syndrome, but pathways affected by GTF2I are indistinct. We first constructed dynamic spatiotemporal networks of 7q11.23 genes by combining data from the brain developmental transcriptome with physical interactions of 7q11.23 proteins. Topological changes were observed in protein–protein interaction (PPI) networks throughout different stages of brain development. Early and late fetal periods of development in the cortex, striatum, hippocampus, and amygdale were observed as the vital periods and regions for 7q11.23 CNV proteins. CNV proteins and their partners are significantly enriched in DNA repair pathway. As a driver gene, GTF2I interacted with PRKDC and BRCA1 to involve in DNA repair pathway. The physical interaction between GTF2I with PRKDC was confirmed experimentally by the liquid chromatography-tandem mass spectrometry (LC–MS/MS). We identified that early and late fetal periods are crucial for 7q11.23 genes to affect brain development. Our results implicate that 7q11.23 CNV genes converge on the DNA repair pathway to contribute to the pathogenesis of psychiatric diseases.
format	article
author	Liang Chen Weidi Wang Wenxiang Cai Weichen Song Wei Qian Guan Ning Lin
author_facet	Liang Chen Weidi Wang Wenxiang Cai Weichen Song Wei Qian Guan Ning Lin
author_sort	Liang Chen
title	Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development
title_short	Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development
title_full	Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development
title_fullStr	Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development
title_full_unstemmed	Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development
title_sort	spatiotemporal 7q11.23 protein network analysis implicates the role of dna repair pathway during human brain development
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/880c847ab3384d7fa5f731deebc2754e
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Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development

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