为了筛选鸡IFIT5基因潜在的、具有生物学功能的nsSNPs(nonsense Single nucleotide polymorphisms,SNPs)位点和UTR-SNPs(untranslated regions-SNPs)位点。利用5种SNPs在线工具对nsSNPs进行分析预测有害位点;使用SWISS-MODEL,Pymol,Cons...为了筛选鸡IFIT5基因潜在的、具有生物学功能的nsSNPs(nonsense Single nucleotide polymorphisms,SNPs)位点和UTR-SNPs(untranslated regions-SNPs)位点。利用5种SNPs在线工具对nsSNPs进行分析预测有害位点;使用SWISS-MODEL,Pymol,Consurf server等软件对有害nsSNPs位点进行蛋白质的空间结构,氨基酸的氢键变化,及保守型等进行相关分析。此外,对UTR-SNPs位点使用UTRScan分析预测其结合模式元件是否改变。结果表明:从IFIT5基因的nsSNPs位点筛选出来的6个有害nsSNPs位点(L220I,L223M,L223V,Y375C,E391G和Y414D)都为潜在性功能位点,其中E391G位点最可能影响蛋白的结构和功能。从UTR-SNPs筛选出9个位于uORF的位点可能影响IFIT5基因的转录模式。展开更多
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 mic...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.展开更多
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
文摘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.
