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Variation in the Large-Scale Organization of Gene Expression Levels in the Hippocampus Relates to Stable Epigenetic Variability in Behavior

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Title: Variation in the Large-Scale Organization of Gene Expression Levels in the Hippocampus Relates to Stable Epigenetic Variability in Behavior
Authors: Alter, Mark D., Rubin, Daniel B., Ramsey, Keri, Halpern, Rebecca, Stephan, Dietrich A., Abbott, Larry, Hen, Rene
Publisher Information: Public Library of Science
Publication Year: 2008
Collection: Columbia University: Academic Commons
Subject Terms: Gene expression, Behavior genetics, DNA microarrays--Data processing, Hippocampus (Brain), Genetics, Medical sciences, Neurosciences
Description: Background Despite sharing the same genes, identical twins demonstrate substantial variability in behavioral traits and in their risk for disease. Epigenetic factors–DNA and chromatin modifications that affect levels of gene expression without affecting the DNA sequence–are thought to be important in establishing this variability. Epigenetically-mediated differences in the levels of gene expression that are associated with individual variability traditionally are thought to occur only in a gene-specific manner. We challenge this idea by exploring the large-scale organizational patterns of gene expression in an epigenetic model of behavioral variability. Methodology/Findings To study the effects of epigenetic influences on behavioral variability, we examine gene expression in genetically identical mice. Using a novel approach to microarray analysis, we show that variability in the large-scale organization of gene expression levels, rather than differences in the expression levels of specific genes, is associated with individual differences in behavior. Specifically, increased activity in the open field is associated with increased variance of log-transformed measures of gene expression in the hippocampus, a brain region involved in open field activity. Early life experience that increases adult activity in the open field also similarly modifies the variance of gene expression levels. The same association of the variance of gene expression levels with behavioral variability is found with levels of gene expression in the hippocampus of genetically heterogeneous outbred populations of mice, suggesting that variation in the large-scale organization of gene expression levels may also be relevant to phenotypic differences in outbred populations such as humans. We find that the increased variance in gene expression levels is attributable to an increasing separation of several large, log-normally distributed families of gene expression levels. We also show that the presence of these multiple log-normal distributions of ...
Document Type: article in journal/newspaper
Language: English
Relation: https://doi.org/10.7916/D8WW7HJ3
DOI: 10.7916/D8WW7HJ3
Availability: https://doi.org/10.7916/D8WW7HJ3
Accession Number: edsbas.542787F6
Database: BASE
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  Data: Variation in the Large-Scale Organization of Gene Expression Levels in the Hippocampus Relates to Stable Epigenetic Variability in Behavior
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  Data: <searchLink fieldCode="AR" term="%22Alter%2C+Mark+D%2E%22">Alter, Mark D.</searchLink><br /><searchLink fieldCode="AR" term="%22Rubin%2C+Daniel+B%2E%22">Rubin, Daniel B.</searchLink><br /><searchLink fieldCode="AR" term="%22Ramsey%2C+Keri%22">Ramsey, Keri</searchLink><br /><searchLink fieldCode="AR" term="%22Halpern%2C+Rebecca%22">Halpern, Rebecca</searchLink><br /><searchLink fieldCode="AR" term="%22Stephan%2C+Dietrich+A%2E%22">Stephan, Dietrich A.</searchLink><br /><searchLink fieldCode="AR" term="%22Abbott%2C+Larry%22">Abbott, Larry</searchLink><br /><searchLink fieldCode="AR" term="%22Hen%2C+Rene%22">Hen, Rene</searchLink>
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  Data: Public Library of Science
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  Data: 2008
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  Data: Columbia University: Academic Commons
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  Data: <searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink><br /><searchLink fieldCode="DE" term="%22Behavior+genetics%22">Behavior genetics</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+microarrays--Data+processing%22">DNA microarrays--Data processing</searchLink><br /><searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Genetics%22">Genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+sciences%22">Medical sciences</searchLink><br /><searchLink fieldCode="DE" term="%22Neurosciences%22">Neurosciences</searchLink>
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  Label: Description
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  Data: Background Despite sharing the same genes, identical twins demonstrate substantial variability in behavioral traits and in their risk for disease. Epigenetic factors–DNA and chromatin modifications that affect levels of gene expression without affecting the DNA sequence–are thought to be important in establishing this variability. Epigenetically-mediated differences in the levels of gene expression that are associated with individual variability traditionally are thought to occur only in a gene-specific manner. We challenge this idea by exploring the large-scale organizational patterns of gene expression in an epigenetic model of behavioral variability. Methodology/Findings To study the effects of epigenetic influences on behavioral variability, we examine gene expression in genetically identical mice. Using a novel approach to microarray analysis, we show that variability in the large-scale organization of gene expression levels, rather than differences in the expression levels of specific genes, is associated with individual differences in behavior. Specifically, increased activity in the open field is associated with increased variance of log-transformed measures of gene expression in the hippocampus, a brain region involved in open field activity. Early life experience that increases adult activity in the open field also similarly modifies the variance of gene expression levels. The same association of the variance of gene expression levels with behavioral variability is found with levels of gene expression in the hippocampus of genetically heterogeneous outbred populations of mice, suggesting that variation in the large-scale organization of gene expression levels may also be relevant to phenotypic differences in outbred populations such as humans. We find that the increased variance in gene expression levels is attributable to an increasing separation of several large, log-normally distributed families of gene expression levels. We also show that the presence of these multiple log-normal distributions of ...
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      – SubjectFull: Behavior genetics
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      – SubjectFull: DNA microarrays--Data processing
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      – TitleFull: Variation in the Large-Scale Organization of Gene Expression Levels in the Hippocampus Relates to Stable Epigenetic Variability in Behavior
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