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Autism and Increased Paternal Age Related Changes in Global Levels of Gene Expression Regulation

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Title: Autism and Increased Paternal Age Related Changes in Global Levels of Gene Expression Regulation
Authors: Alter, Mark D., Kharkar, Rutwik, Ramsey, Keri E., Craig, David W., Melmed, Raun D., Grebe, Theresa A., Bay, R. Curtis, Ober-Reynolds, Sharman, Kirwan, Janet, Jones, Josh J., Turner, J. Blake, Hen, Rene, Stephan, Dietrich A.
Publisher Information: Public Library of Science
Publication Year: 2011
Collection: Columbia University: Academic Commons
Subject Terms: Autism--Etiology, DNA microarrays--Data processing, Genetic regulation, Genetics, Molecular biology, Medical sciences
Description: A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL) of children with autism (n = 82) and controls (n = 64). Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.
Document Type: article in journal/newspaper
Language: English
Relation: https://doi.org/10.7916/D8DV1JR7
DOI: 10.7916/D8DV1JR7
Availability: https://doi.org/10.7916/D8DV1JR7
Accession Number: edsbas.4F9C0981
Database: BASE
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  Data: Autism and Increased Paternal Age Related Changes in Global Levels of Gene Expression Regulation
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  Data: <searchLink fieldCode="AR" term="%22Alter%2C+Mark+D%2E%22">Alter, Mark D.</searchLink><br /><searchLink fieldCode="AR" term="%22Kharkar%2C+Rutwik%22">Kharkar, Rutwik</searchLink><br /><searchLink fieldCode="AR" term="%22Ramsey%2C+Keri+E%2E%22">Ramsey, Keri E.</searchLink><br /><searchLink fieldCode="AR" term="%22Craig%2C+David+W%2E%22">Craig, David W.</searchLink><br /><searchLink fieldCode="AR" term="%22Melmed%2C+Raun+D%2E%22">Melmed, Raun D.</searchLink><br /><searchLink fieldCode="AR" term="%22Grebe%2C+Theresa+A%2E%22">Grebe, Theresa A.</searchLink><br /><searchLink fieldCode="AR" term="%22Bay%2C+R%2E+Curtis%22">Bay, R. Curtis</searchLink><br /><searchLink fieldCode="AR" term="%22Ober-Reynolds%2C+Sharman%22">Ober-Reynolds, Sharman</searchLink><br /><searchLink fieldCode="AR" term="%22Kirwan%2C+Janet%22">Kirwan, Janet</searchLink><br /><searchLink fieldCode="AR" term="%22Jones%2C+Josh+J%2E%22">Jones, Josh J.</searchLink><br /><searchLink fieldCode="AR" term="%22Turner%2C+J%2E+Blake%22">Turner, J. Blake</searchLink><br /><searchLink fieldCode="AR" term="%22Hen%2C+Rene%22">Hen, Rene</searchLink><br /><searchLink fieldCode="AR" term="%22Stephan%2C+Dietrich+A%2E%22">Stephan, Dietrich A.</searchLink>
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  Data: 2011
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  Data: A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL) of children with autism (n = 82) and controls (n = 64). Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.
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