Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.

Random or stochastic monoallelic expressed genes (StMA genes) represent a unique form of monoallelic expression where allelic choice is made at random early in development. The consequential clonal diversity provides opportunity for functional heterozygosity in tissues such as the brain, and can imp...

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Autores principales:	Aaron R Jeffries, David A Collier, Evangelos Vassos, Sarah Curran, Caroline M Ogilvie, Jack Price
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b30d26637f4346c4be34bc0525abbfb6
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spelling	oai:doaj.org-article:b30d26637f4346c4be34bc0525abbfb62021-11-18T08:40:00ZRandom or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.1932-620310.1371/journal.pone.0085093https://doaj.org/article/b30d26637f4346c4be34bc0525abbfb62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386451/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Random or stochastic monoallelic expressed genes (StMA genes) represent a unique form of monoallelic expression where allelic choice is made at random early in development. The consequential clonal diversity provides opportunity for functional heterozygosity in tissues such as the brain, and can impact on both development and disease. We investigate the relationship of StMA expressed genes previously identified in clonal neural stem cells with the neurodevelopmental disorders autism and schizophrenia. We found that StMA genes show an overrepresentation of schizophrenia risk candidates identified by genome wide association studies from the genetic association database. Similar suggestive enrichment was also found for genes from the NHGRI genome-wide association study catalog and a psychiatric genetics consortium schizophrenia dataset although these latter more robust gene lists did not achieve statistical significance. We also examined multiple sources of copy number variation (CNV) datasets from autism and schizophrenia cohorts. After taking into account total gene numbers and CNV size, both autism and schizophrenia associated CNVs appeared to show an enrichment of StMA genes relative to the control CNV datasets. Since the StMA genes were originally identified in neural stem cells, bias due to the neural transcriptome is possible. To address this, we randomly sampled neural stem cell expressed genes and repeated the tests. After a significant number of iterations, neural stem cell expressed genes did not show an overrepresentation in autism or schizophrenia CNV datasets. Therefore, irrespective of the neural derived transcriptome, StMA genes originally identified in neural stem cells show an overrepresentation in CNVs associated with autism and schizophrenia. If this association is functional, then the regulation (or dysregulation) of this form of allelic expression status within tissues such as the brain may be a contributory risk factor for neurodevelopmental disorders and may also influence disease discordance sometimes observed in monozygotic twins.Aaron R JeffriesDavid A CollierEvangelos VassosSarah CurranCaroline M OgilvieJack PricePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e85093 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aaron R Jeffries David A Collier Evangelos Vassos Sarah Curran Caroline M Ogilvie Jack Price Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.
description	Random or stochastic monoallelic expressed genes (StMA genes) represent a unique form of monoallelic expression where allelic choice is made at random early in development. The consequential clonal diversity provides opportunity for functional heterozygosity in tissues such as the brain, and can impact on both development and disease. We investigate the relationship of StMA expressed genes previously identified in clonal neural stem cells with the neurodevelopmental disorders autism and schizophrenia. We found that StMA genes show an overrepresentation of schizophrenia risk candidates identified by genome wide association studies from the genetic association database. Similar suggestive enrichment was also found for genes from the NHGRI genome-wide association study catalog and a psychiatric genetics consortium schizophrenia dataset although these latter more robust gene lists did not achieve statistical significance. We also examined multiple sources of copy number variation (CNV) datasets from autism and schizophrenia cohorts. After taking into account total gene numbers and CNV size, both autism and schizophrenia associated CNVs appeared to show an enrichment of StMA genes relative to the control CNV datasets. Since the StMA genes were originally identified in neural stem cells, bias due to the neural transcriptome is possible. To address this, we randomly sampled neural stem cell expressed genes and repeated the tests. After a significant number of iterations, neural stem cell expressed genes did not show an overrepresentation in autism or schizophrenia CNV datasets. Therefore, irrespective of the neural derived transcriptome, StMA genes originally identified in neural stem cells show an overrepresentation in CNVs associated with autism and schizophrenia. If this association is functional, then the regulation (or dysregulation) of this form of allelic expression status within tissues such as the brain may be a contributory risk factor for neurodevelopmental disorders and may also influence disease discordance sometimes observed in monozygotic twins.
format	article
author	Aaron R Jeffries David A Collier Evangelos Vassos Sarah Curran Caroline M Ogilvie Jack Price
author_facet	Aaron R Jeffries David A Collier Evangelos Vassos Sarah Curran Caroline M Ogilvie Jack Price
author_sort	Aaron R Jeffries
title	Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.
title_short	Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.
title_full	Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.
title_fullStr	Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.
title_full_unstemmed	Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.
title_sort	random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b30d26637f4346c4be34bc0525abbfb6
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Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes.

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