Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex
Abstract Background Genetic studies in autism have pinpointed a heterogeneous group of loci and genes. Further, environment may be an additional factor conferring susceptibility to autism. Transcriptome studies investigate quantitative differences in gene expression between patient-derived tissues a...
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doaj-a43d93e689e243578493a25a6b22a5a92020-11-25T01:03:02ZengBMCJournal of Neurodevelopmental Disorders1866-19471866-19552018-06-011011910.1186/s11689-018-9237-xStrong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortexMatthew Schwede0Shailender Nagpal1Michael J. Gandal2Neelroop N. Parikshak3Karoly Mirnics4Daniel H. Geschwind5Eric M. Morrow6Department of Molecular Biology, Cell Biology and Biochemistry, and Carney Institute for Brain Science, Brown UniversityDepartment of Molecular Biology, Cell Biology and Biochemistry, and Carney Institute for Brain Science, Brown UniversityDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los AngelesDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los AngelesDepartment of Psychiatry and Kennedy Center for Research on Human Development, Vanderbilt UniversityDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los AngelesDepartment of Molecular Biology, Cell Biology and Biochemistry, and Carney Institute for Brain Science, Brown UniversityAbstract Background Genetic studies in autism have pinpointed a heterogeneous group of loci and genes. Further, environment may be an additional factor conferring susceptibility to autism. Transcriptome studies investigate quantitative differences in gene expression between patient-derived tissues and control. These studies may pinpoint genes relevant to pathophysiology yet circumvent the need to understand genetic architecture or gene-by-environment interactions leading to disease. Methods We conducted alternate gene set enrichment analyses using differentially expressed genes from a previously published RNA-seq study of post-mortem autism cerebral cortex. We used three previously published microarray datasets for validation and one of the microarray datasets for additional differential expression analysis. The RNA-seq study used 26 autism and 33 control brains in differential gene expression analysis, and the largest microarray dataset contained 15 autism and 16 control post-mortem brains. Results While performing a gene set enrichment analysis of genes differentially expressed in the RNA-seq study, we discovered that genes associated with mitochondrial function were downregulated in autism cerebral cortex, as compared to control. These genes were correlated with genes related to synaptic function. We validated these findings across the multiple microarray datasets. We also did separate differential expression and gene set enrichment analyses to confirm the importance of the mitochondrial pathway among downregulated genes in post-mortem autism cerebral cortex. Conclusions We found that genes related to mitochondrial function were differentially expressed in autism cerebral cortex and correlated with genes related to synaptic transmission. Our principal findings replicate across all datasets investigated. Further, these findings may potentially replicate in other diseases, such as in schizophrenia.http://link.springer.com/article/10.1186/s11689-018-9237-xAutismHumanCortexPost-mortemTranscriptome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew Schwede Shailender Nagpal Michael J. Gandal Neelroop N. Parikshak Karoly Mirnics Daniel H. Geschwind Eric M. Morrow |
spellingShingle |
Matthew Schwede Shailender Nagpal Michael J. Gandal Neelroop N. Parikshak Karoly Mirnics Daniel H. Geschwind Eric M. Morrow Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex Journal of Neurodevelopmental Disorders Autism Human Cortex Post-mortem Transcriptome |
author_facet |
Matthew Schwede Shailender Nagpal Michael J. Gandal Neelroop N. Parikshak Karoly Mirnics Daniel H. Geschwind Eric M. Morrow |
author_sort |
Matthew Schwede |
title |
Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex |
title_short |
Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex |
title_full |
Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex |
title_fullStr |
Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex |
title_full_unstemmed |
Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex |
title_sort |
strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex |
publisher |
BMC |
series |
Journal of Neurodevelopmental Disorders |
issn |
1866-1947 1866-1955 |
publishDate |
2018-06-01 |
description |
Abstract Background Genetic studies in autism have pinpointed a heterogeneous group of loci and genes. Further, environment may be an additional factor conferring susceptibility to autism. Transcriptome studies investigate quantitative differences in gene expression between patient-derived tissues and control. These studies may pinpoint genes relevant to pathophysiology yet circumvent the need to understand genetic architecture or gene-by-environment interactions leading to disease. Methods We conducted alternate gene set enrichment analyses using differentially expressed genes from a previously published RNA-seq study of post-mortem autism cerebral cortex. We used three previously published microarray datasets for validation and one of the microarray datasets for additional differential expression analysis. The RNA-seq study used 26 autism and 33 control brains in differential gene expression analysis, and the largest microarray dataset contained 15 autism and 16 control post-mortem brains. Results While performing a gene set enrichment analysis of genes differentially expressed in the RNA-seq study, we discovered that genes associated with mitochondrial function were downregulated in autism cerebral cortex, as compared to control. These genes were correlated with genes related to synaptic function. We validated these findings across the multiple microarray datasets. We also did separate differential expression and gene set enrichment analyses to confirm the importance of the mitochondrial pathway among downregulated genes in post-mortem autism cerebral cortex. Conclusions We found that genes related to mitochondrial function were differentially expressed in autism cerebral cortex and correlated with genes related to synaptic transmission. Our principal findings replicate across all datasets investigated. Further, these findings may potentially replicate in other diseases, such as in schizophrenia. |
topic |
Autism Human Cortex Post-mortem Transcriptome |
url |
http://link.springer.com/article/10.1186/s11689-018-9237-x |
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