miRdSNP: a database of disease-associated SNPs and microRNA target sites on 3'UTRs of human genes

BackgroundSingle nucleotide polymorphisms (SNPs) can lead to the susceptibility and onset of diseases through their effects on gene expression at the posttranscriptional level. Recent findings indicate that SNPs could create, destroy, or modify the efficiency of miRNA binding to the 3'UTR of a gene, resulting in gene dysregulation. With the rapidly growing number of published disease-associated SNPs (dSNPs), there is a strong need for resources specifically recording dSNPs on the 3'UTRs and their nucleotide distance from miRNA target sites. We present here miRdSNP, a database incorporating three important areas of dSNPs, miRNA target sites, and diseases.DescriptionmiRdSNP provides a unique database of dSNPs on the 3'UTRs of human genes manually curated from PubMed. The current release includes 786 dSNP-disease associations for 630 unique dSNPs and 204 disease types. miRdSNP annotates genes with experimentally confirmed targeting by miRNAs and indexes miRNA target sites predicted by TargetScan and PicTar as well as potential miRNA target sites newly generated by dSNPs. A robust web interface and search tools are provided for studying the proximity of miRNA binding sites to dSNPs in relation to human diseases. Searches can be dynamically filtered by gene name, miRBase ID, target prediction algorithm, disease, and any nucleotide distance between dSNPs and miRNA target sites. Results can be viewed at the sequence level showing the annotated locations for miRNA target sites and dSNPs on the entire 3'UTR sequences. The integration of dSNPs with the UCSC Genome browser is also supported.ConclusionmiRdSNP provides a comprehensive data source of dSNPs and robust tools for exploring their distance from miRNA target sites on the 3'UTRs of human genes. miRdSNP enables researchers to further explore the molecular mechanism of gene dysregulation for dSNPs at posttranscriptional level. miRdSNP is freely available on the web at http://mirdsnp.ccr.buffalo.edu.

[1]  Elizabeth M. Smigielski,et al.  dbSNP: the NCBI database of genetic variation , 2001, Nucleic Acids Res..

[2]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[3]  Anton J. Enright,et al.  MicroRNA targets in Drosophila , 2003, Genome Biology.

[4]  A. Danchin,et al.  Bmc Genomics , 2004 .

[5]  C. Croce,et al.  The role of microRNA genes in papillary thyroid carcinoma. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[7]  Murat Gunel,et al.  Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome , 2005, Science.

[8]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[9]  A. Hatzigeorgiou,et al.  TarBase: A comprehensive database of experimentally supported animal microRNA targets. , 2005, RNA.

[10]  Mihaela Zavolan,et al.  Inference of miRNA targets using evolutionary conservation and pathway analysis , 2007, BMC Bioinformatics.

[11]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[12]  Carole Ober,et al.  Allele-specific targeting of microRNAs to HLA-G and risk of asthma. , 2007, American journal of human genetics.

[13]  Thomas D. Schmittgen,et al.  The Human Angiotensin II Type 1 Receptor +1166 A/C Polymorphism Attenuates MicroRNA-155 Binding* , 2007, Journal of Biological Chemistry.

[14]  Ligang Wu,et al.  PolymiRTS Database: linking polymorphisms in microRNA target sites with complex traits , 2006, Nucleic Acids Res..

[15]  D. Banerjee,et al.  A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance , 2007, Proceedings of the National Academy of Sciences.

[16]  Zhaohui S. Qin,et al.  A second generation human haplotype map of over 3.1 million SNPs , 2007, Nature.

[17]  R. Petersen,et al.  Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia , 2008, Human molecular genetics.

[18]  F. Slack,et al.  Cancer Risk Small Cell Lung − Untranslated Region Increases Non ′ 3 KRAS microRNA Complementary Site in the let-7 A SNP in a , 2008 .

[19]  Gaofeng Wang,et al.  Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. , 2008, American journal of human genetics.

[20]  Andrew D. Johnson,et al.  SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap , 2008, Bioinform..

[21]  Robert Johansson,et al.  Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer: ITGB4 as prognostic marker. , 2008, Carcinogenesis.

[22]  Tongbin Li,et al.  miRecords: an integrated resource for microRNA–target interactions , 2008, Nucleic Acids Res..

[23]  Nectarios Koziris,et al.  Accurate microRNA target prediction correlates with protein repression levels , 2009, BMC Bioinformatics.

[24]  David Smith,et al.  A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. , 2009, Cancer research.

[25]  Martin Reczko,et al.  Lost in translation: an assessment and perspective for computational microRNA target identification , 2009, Bioinform..

[26]  Yadong Wang,et al.  miR2Disease: a manually curated database for microRNA deregulation in human disease , 2008, Nucleic Acids Res..

[27]  D. Dickson,et al.  Common Variant in GRN Is a Genetic Risk Factor for Hippocampal Sclerosis in the Elderly , 2010, Neurodegenerative Diseases.

[28]  Hyunsoo Kim,et al.  Single-nucleotide polymorphisms inside microRNA target sites influence tumor susceptibility. , 2010, Cancer research.

[29]  Michel Georges,et al.  Patrocles: a database of polymorphic miRNA-mediated gene regulation in vertebrates , 2008, Nucleic Acids Res..

[30]  C. Dörfer,et al.  A 3′ UTR transition within DEFB1 is associated with chronic and aggressive periodontitis , 2010, Genes and Immunity.

[31]  Chi-Ying F. Huang,et al.  miRTarBase: a database curates experimentally validated microRNA–target interactions , 2010, Nucleic Acids Res..

[32]  Andrew E. Bruno,et al.  The Influence of 3′UTRs on MicroRNA Function Inferred from Human SNP Data , 2011, Comparative and functional genomics.

[33]  Jinmai Jiang,et al.  The human angiotensin II type 1 receptor +1166 A/C polymorphism attenuates microRNA-155 binding. , 2013, The Journal of Biological Chemistry.