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Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex
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 contr...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984825/ https://www.ncbi.nlm.nih.gov/pubmed/29859039 http://dx.doi.org/10.1186/s11689-018-9237-x |
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author | Schwede, Matthew Nagpal, Shailender Gandal, Michael J. Parikshak, Neelroop N. Mirnics, Karoly Geschwind, Daniel H. Morrow, Eric M. |
author_facet | Schwede, Matthew Nagpal, Shailender Gandal, Michael J. Parikshak, Neelroop N. Mirnics, Karoly Geschwind, Daniel H. Morrow, Eric M. |
author_sort | Schwede, Matthew |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s11689-018-9237-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5984825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59848252018-06-07 Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex Schwede, Matthew Nagpal, Shailender Gandal, Michael J. Parikshak, Neelroop N. Mirnics, Karoly Geschwind, Daniel H. Morrow, Eric M. J Neurodev Disord Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s11689-018-9237-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-01 /pmc/articles/PMC5984825/ /pubmed/29859039 http://dx.doi.org/10.1186/s11689-018-9237-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Schwede, Matthew Nagpal, Shailender Gandal, Michael J. Parikshak, Neelroop N. Mirnics, Karoly Geschwind, Daniel H. Morrow, Eric M. Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex |
title | 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_short | 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 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984825/ https://www.ncbi.nlm.nih.gov/pubmed/29859039 http://dx.doi.org/10.1186/s11689-018-9237-x |
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