Insights on the functional impact of microRNAs present in autism-associated copy number variants.
Autism spectrum disorder is a complex neurodevelopmental disorder that appears during the first three years of infancy and lasts throughout a person's life. Recently a large category of genomic structural variants, denoted as copy number variants (CNVs), were established to be a major contribut...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3581547?pdf=render |
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| author | Varadarajan Vaishnavi Mayakannan Manikandan Basant K Tiwary Arasambattu Kannan Munirajan |
| author_facet | Varadarajan Vaishnavi Mayakannan Manikandan Basant K Tiwary Arasambattu Kannan Munirajan |
| author_sort | Varadarajan Vaishnavi |
| collection | DOAJ |
| description | Autism spectrum disorder is a complex neurodevelopmental disorder that appears during the first three years of infancy and lasts throughout a person's life. Recently a large category of genomic structural variants, denoted as copy number variants (CNVs), were established to be a major contributor of the pathophysiology of autism. To date almost all studies have focussed only on the genes present in the CNV loci, but the impact of non-coding regulatory microRNAs (miRNAs) present in these regions remain largely unexplored. Hence we attempted to elucidate the biological and functional significance of miRNAs present in autism-associated CNV loci and their target genes by using a series of computational tools. We demonstrate that nearly 11% of the CNV loci harbor miRNAs and a few of these miRNAs were previously reported to be associated with autism. A systematic analysis of the CNV-miRNAs based on their interactions with the target genes enabled the identification of top 10 miRNAs namely hsa-miR-590-3p, hsa-miR-944, hsa-miR-570, hsa-miR-34a, hsa-miR-124, hsa-miR-548f, hsa-miR-429, hsa-miR-200b, hsa-miR-195 and hsa-miR-497 as hub molecules. Further, the CNV-miRNAs formed a regulatory loop with transcription factors and their downstream target genes, and annotation of these target genes indicated their functional involvement in neurodevelopment and synapse. Moreover, miRNAs present in deleted and duplicated CNV loci may explain the difference in dosage of the crucial genes controlled by them. These CNV-miRNAs can also impair the global processing and biogenesis of all miRNAs by targeting key molecules in the miRNA pathway. To our knowledge, this is the first report to highlight the significance of CNV-microRNAs and their target genes to contribute towards the genetic heterogeneity and phenotypic variability of autism. |
| first_indexed | 2024-12-23T23:47:17Z |
| format | Article |
| id | doaj.art-62919e2439b94572ac15299cec4f28e1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T23:47:17Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-62919e2439b94572ac15299cec4f28e12022-12-21T17:25:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5678110.1371/journal.pone.0056781Insights on the functional impact of microRNAs present in autism-associated copy number variants.Varadarajan VaishnaviMayakannan ManikandanBasant K TiwaryArasambattu Kannan MunirajanAutism spectrum disorder is a complex neurodevelopmental disorder that appears during the first three years of infancy and lasts throughout a person's life. Recently a large category of genomic structural variants, denoted as copy number variants (CNVs), were established to be a major contributor of the pathophysiology of autism. To date almost all studies have focussed only on the genes present in the CNV loci, but the impact of non-coding regulatory microRNAs (miRNAs) present in these regions remain largely unexplored. Hence we attempted to elucidate the biological and functional significance of miRNAs present in autism-associated CNV loci and their target genes by using a series of computational tools. We demonstrate that nearly 11% of the CNV loci harbor miRNAs and a few of these miRNAs were previously reported to be associated with autism. A systematic analysis of the CNV-miRNAs based on their interactions with the target genes enabled the identification of top 10 miRNAs namely hsa-miR-590-3p, hsa-miR-944, hsa-miR-570, hsa-miR-34a, hsa-miR-124, hsa-miR-548f, hsa-miR-429, hsa-miR-200b, hsa-miR-195 and hsa-miR-497 as hub molecules. Further, the CNV-miRNAs formed a regulatory loop with transcription factors and their downstream target genes, and annotation of these target genes indicated their functional involvement in neurodevelopment and synapse. Moreover, miRNAs present in deleted and duplicated CNV loci may explain the difference in dosage of the crucial genes controlled by them. These CNV-miRNAs can also impair the global processing and biogenesis of all miRNAs by targeting key molecules in the miRNA pathway. To our knowledge, this is the first report to highlight the significance of CNV-microRNAs and their target genes to contribute towards the genetic heterogeneity and phenotypic variability of autism.http://europepmc.org/articles/PMC3581547?pdf=render |
| spellingShingle | Varadarajan Vaishnavi Mayakannan Manikandan Basant K Tiwary Arasambattu Kannan Munirajan Insights on the functional impact of microRNAs present in autism-associated copy number variants. PLoS ONE |
| title | Insights on the functional impact of microRNAs present in autism-associated copy number variants. |
| title_full | Insights on the functional impact of microRNAs present in autism-associated copy number variants. |
| title_fullStr | Insights on the functional impact of microRNAs present in autism-associated copy number variants. |
| title_full_unstemmed | Insights on the functional impact of microRNAs present in autism-associated copy number variants. |
| title_short | Insights on the functional impact of microRNAs present in autism-associated copy number variants. |
| title_sort | insights on the functional impact of micrornas present in autism associated copy number variants |
| url | http://europepmc.org/articles/PMC3581547?pdf=render |
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