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Mining the 3′UTR of Autism-implicated Genes for SNPs Perturbing MicroRNA Regulation

查看全文 作　　者：Varadharajan [1]Vaishnavi;Mayakannan [1]Manikandan;Arasambattu Kannan [1]Munirajan 高影响力作者 机构地区：[1]Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras高影响力机构 出　　处：《Genomics, Proteomics & Bioinformatics》索引2014年第12卷第2期,共13页高影响力期刊 基　　金：supported by a grant from the Depart-ment of Biotechnology,New Delhi,India to AKM(Grant No.BT/PR10023/AGR/36/27/2007);supported by a research fellowship from the Council of Scientific and Indus-trial Research,New Delhi 摘　　要：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 30untranslated region(30UTR) 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 30UTRs 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 30UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation. 关 键 词：多基因遗传 SNPS MICRORNA 自闭 扰动 单核苷酸多态性 miRNA 矿业
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