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A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set
Molecular underpinnings of complex psychiatric disorders such as autism spectrum disorders (ASD) remain largely unresolved. Increasingly, structural variations in discrete chromosomal loci are implicated in ASD, expanding the search space for its disease etiology. We exploited the high genetic heter...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235126/ https://www.ncbi.nlm.nih.gov/pubmed/22174805 http://dx.doi.org/10.1371/journal.pone.0028431 |
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author | Kumar, Ajay Swanwick, Catherine Croft Johnson, Nicole Menashe, Idan Basu, Saumyendra N. Bales, Michael E. Banerjee-Basu, Sharmila |
author_facet | Kumar, Ajay Swanwick, Catherine Croft Johnson, Nicole Menashe, Idan Basu, Saumyendra N. Bales, Michael E. Banerjee-Basu, Sharmila |
author_sort | Kumar, Ajay |
collection | PubMed |
description | Molecular underpinnings of complex psychiatric disorders such as autism spectrum disorders (ASD) remain largely unresolved. Increasingly, structural variations in discrete chromosomal loci are implicated in ASD, expanding the search space for its disease etiology. We exploited the high genetic heterogeneity of ASD to derive a predictive map of candidate genes by an integrated bioinformatics approach. Using a reference set of 84 Rare and Syndromic candidate ASD genes (AutRef84), we built a composite reference profile based on both functional and expression analyses. First, we created a functional profile of AutRef84 by performing Gene Ontology (GO) enrichment analysis which encompassed three main areas: 1) neurogenesis/projection, 2) cell adhesion, and 3) ion channel activity. Second, we constructed an expression profile of AutRef84 by conducting DAVID analysis which found enrichment in brain regions critical for sensory information processing (olfactory bulb, occipital lobe), executive function (prefrontal cortex), and hormone secretion (pituitary). Disease specificity of this dual AutRef84 profile was demonstrated by comparative analysis with control, diabetes, and non-specific gene sets. We then screened the human genome with the dual AutRef84 profile to derive a set of 460 potential ASD candidate genes. Importantly, the power of our predictive gene map was demonstrated by capturing 18 existing ASD-associated genes which were not part of the AutRef84 input dataset. The remaining 442 genes are entirely novel putative ASD risk genes. Together, we used a composite ASD reference profile to generate a predictive map of novel ASD candidate genes which should be prioritized for future research. |
format | Online Article Text |
id | pubmed-3235126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32351262011-12-15 A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set Kumar, Ajay Swanwick, Catherine Croft Johnson, Nicole Menashe, Idan Basu, Saumyendra N. Bales, Michael E. Banerjee-Basu, Sharmila PLoS One Research Article Molecular underpinnings of complex psychiatric disorders such as autism spectrum disorders (ASD) remain largely unresolved. Increasingly, structural variations in discrete chromosomal loci are implicated in ASD, expanding the search space for its disease etiology. We exploited the high genetic heterogeneity of ASD to derive a predictive map of candidate genes by an integrated bioinformatics approach. Using a reference set of 84 Rare and Syndromic candidate ASD genes (AutRef84), we built a composite reference profile based on both functional and expression analyses. First, we created a functional profile of AutRef84 by performing Gene Ontology (GO) enrichment analysis which encompassed three main areas: 1) neurogenesis/projection, 2) cell adhesion, and 3) ion channel activity. Second, we constructed an expression profile of AutRef84 by conducting DAVID analysis which found enrichment in brain regions critical for sensory information processing (olfactory bulb, occipital lobe), executive function (prefrontal cortex), and hormone secretion (pituitary). Disease specificity of this dual AutRef84 profile was demonstrated by comparative analysis with control, diabetes, and non-specific gene sets. We then screened the human genome with the dual AutRef84 profile to derive a set of 460 potential ASD candidate genes. Importantly, the power of our predictive gene map was demonstrated by capturing 18 existing ASD-associated genes which were not part of the AutRef84 input dataset. The remaining 442 genes are entirely novel putative ASD risk genes. Together, we used a composite ASD reference profile to generate a predictive map of novel ASD candidate genes which should be prioritized for future research. Public Library of Science 2011-12-09 /pmc/articles/PMC3235126/ /pubmed/22174805 http://dx.doi.org/10.1371/journal.pone.0028431 Text en Kumar et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kumar, Ajay Swanwick, Catherine Croft Johnson, Nicole Menashe, Idan Basu, Saumyendra N. Bales, Michael E. Banerjee-Basu, Sharmila A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set |
title | A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set |
title_full | A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set |
title_fullStr | A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set |
title_full_unstemmed | A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set |
title_short | A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set |
title_sort | brain region-specific predictive gene map for autism derived by profiling a reference gene set |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235126/ https://www.ncbi.nlm.nih.gov/pubmed/22174805 http://dx.doi.org/10.1371/journal.pone.0028431 |
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