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SNPSplicer: systematic analysis of SNP‐dependent splicing in genotyped cDNAs
Author(s) -
ElSharawy Abdou,
Manaster Carl,
Teuber Markus,
Rosenstiel Philip,
Kwiatkowski Ruta,
Huse Klaus,
Platzer Matthias,
Becker Albert,
Nürnberg Peter,
Schreiber Stefan,
Hampe Jochen
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20377
Subject(s) - biology , rna splicing , splice , genetics , enhancer , single nucleotide polymorphism , exon , minigene , exonic splicing enhancer , exon skipping , international hapmap project , alternative splicing , computational biology , snp genotyping , splice site mutation , gene , genotype , rna , gene expression
Functional annotation of SNPs (as generated by HapMap (http://www.hapmap.org) for instance) is a major challenge. SNPs that lead to single amino acid substitutions, stop codons, or frameshift mutations can be readily interpreted, but these represent only a fraction of known SNPs. Many SNPs are located in sequences of splicing relevance-the canonical splice site consensus sequences, exonic and intronic splice enhancers or silencers (exonic splice enhancer [ESE], intronic splice enhancer [ISE], exonic splicing silencer [ESS], and intronic splicing silencer [ISS]), and others. We propose using sets of matching DNA and complementary DNA (cDNA) as a screening method to investigate the potential splice effects of SNPs in RT-PCR experiments with tissue material from genotyped sources. We have developed a software solution (SNPSplicer; http://www.ikmb.uni-kiel.de/snpsplicer) that aids in the rapid interpretation of such screening experiments. The utility of the approach is illustrated for SNPs affecting the donor splice sites (rs2076530:A>G, rs3816989:G>A) leading to the use of a cryptic splice site and exon skipping, respectively, and an exonic splice enhancer SNP (rs2274987:C/T), leading to inclusion of a new exon. We anticipate that this methodology may help in the functional annotation of SNPs in a more high-throughput fashion.