Mining the 30UTR of Autism-implicated Genes for SNPs Perturbing MicroRNA Regulation |
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Authors: | Varadharajan Vaishnavi Mayakannan Manikandan Arasambattu Kannan Munirajan |
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Affiliation: | Varadharajan Vaishnavi(Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India);Mayakannan Manikandan(Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India);Arasambattu Kannan Munirajan(Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India); |
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Abstract: | Autism spectrum disorder (ASD) refers to a group of childhood neurodevelopmental dis-orders with polygenic etiology. The expression of many genes implicated in ASD is tightly regulated by various factors including microRNAs (miRNAs), a class of noncoding RNAs 22 nucleotides in length that function to suppress translation by pairing with‘miRNA recognition elements’ (MREs) present in the 30untranslated region (30UTR) of target mRNAs. This emphasizes the role played by miRNAs in regulating neurogenesis, brain development and differentiation and hence any perturba-tions in this regulatory mechanism might affect these processes as well. Recently, single nucleotide polymorphisms (SNPs) present within 30UTRs of mRNAs have been shown to modulate existing MREs or even create new MREs. Therefore, we hypothesized that SNPs perturbing miRNA-medi-ated gene regulation might lead to aberrant expression of autism-implicated genes, thus resulting in disease predisposition or pathogenesis in at least a subpopulation of ASD individuals. We developed a systematic computational pipeline that integrates data from well-established databases. By following a stringent selection criterion, we identified 9 MRE-modulating SNPs and another 12 MRE-creating SNPs in the 30UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation. |
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Keywords: | Autism spectrum disorder MicroRNA Single nucleotide polymorphism 30UTR-SNP Gene regulation |
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