PupaSNP Finder: a web tool for finding SNPs with putative effect at transcriptional level

Abstract

We have developed a web tool, PupaSNP Finder (PupaSNP for short), for high-throughput searching for single nucleotide polymorphisms (SNPs) with potential phenotypic effect. PupaSNP takes as its input lists of genes (or generates them from chromosomal coordinates) and retrieves SNPs that could affect the conserved regions that the cellular machinery uses for the correct processing of genes (intron/exon boundaries or exonic splicing enhancers), predicted transcription factor binding sites (TFBS) and changes in amino acids in the proteins. The program uses the mapping of SNPs in the genome provided by Ensembl. Additionally, user-defined SNPs (not yet mapped in the genome) can be easily provided to the program. Also, additional functional information from Gene Ontology, OMIM and homologies in other model organisms is provided. In contrast to other programs already available, which focus only on SNPs with possible effect in the protein, PupaSNP includes SNPs with possible transcriptional effect. PupaSNP will be of significant help in studies of multifactorial disorders, where the use of functional SNPs will increase the sensitivity of identification of the genes responsible for the disease. The PupaSNP web interface is accessible through http://pupasnp.bioinfo.cnio.es.

Figure 1

A selection of results from PupaSNP. (A) List of genes and the corresponding transcripts with the SNPs mapping to the different regions, which include coding and 5′- and 3′-untranslated regions. For coding SNPs, the position within the transcript and the change produced (if any) is reported. (B) SNPs located in the promoter regions (in the example, a limit of 4000 bp was chosen). Disruptions of predicted TFBSs are listed. The validation status of the SNPs (‘no-info’, ‘by-submitter’, ‘by-frequency’, ‘by-cluster’; see dbSNP web page) is also provided. (C) SNPs located at exonic splice enhancers. The scores make reference to the closeness of the site to the motif. If the polymorphism gives a site with a worst score, this would, generally speaking, probably imply worst recognition of the site by the cellular machinery and, consequently, a putative alteration in the normal splicing process. When the cursor is over the gene name, additional information is displayed.