SNPSplicer: systematic analysis of SNP-dependent splicing in genotyped cDNAs

Hum Mutat. 2006 Nov;27(11):1129-34. doi: 10.1002/humu.20377.


Functional annotation of SNPs (as generated by HapMap ( 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; 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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / physiology
  • Base Sequence
  • Brain / cytology
  • Cell Line, Tumor
  • DNA / blood
  • DNA Mutational Analysis / methods
  • DNA, Complementary / analysis*
  • Electronic Data Processing / methods
  • Genotype*
  • Humans
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide*
  • RNA Splice Sites / genetics*
  • Software*


  • DNA, Complementary
  • RNA Splice Sites
  • DNA