title: Mining the 3'UTR of autism-implicated genes for SNPs perturbing microRNA regulation.
abstract: Autism spectrum disorder (ASD) refers to a group of childhood neurodevelopmental disorders 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 3'untranslated region (3'UTR) of target mRNAs. This emphasizes the role played by miRNAs in regulating neurogenesis, brain development and differentiation and hence any perturbations in this regulatory mechanism might affect these processes as well. Recently, single nucleotide polymorphisms (SNPs) present within 3'UTRs of mRNAs have been shown to modulate existing MREs or even create new MREs. Therefore, we hypothesized that SNPs perturbing miRNA-mediated 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 3'UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation.
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
authors.forename: Varadharajan
authors.initials: V
authors.lastname: Vaishnavi
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
authors.forename: Mayakannan
authors.initials: M
authors.lastname: Manikandan
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India. Electronic address: akmunirajan@unom.ac.in.
authors.forename: Arasambattu Kannan
authors.initials: AK
authors.lastname: Munirajan
mesh_terms: D020413:3' Untranslated Regions; D001321:Autistic Disorder / Q000235:genetics*; D001483:Base Sequence; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009690:Nucleic Acid Conformation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs
keywords: 3′UTR-SNP; Autism spectrum disorder; Gene regulation; MicroRNA; Single nucleotide polymorphism
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