Intronic CpG content and alternative splicing in human genes containing a single cassette exon

Clinical data provide evidence for the association of missplicing with methyl-binding protein mutations and inhibition of methylation. In this study, we analyzed a 373 human gene database containing a single alternatively spliced exon (cassette) and 1,039 constitutive introns, and showed that CpG frequencies are higher in alternative compared to constitutive introns, particularly in donors preceding cassette exons (p < 0.0001). Donors with more than three CpGs within 50 nt from splice junctions are mostly upstream alternative (21.83% vs. 3.21% for constitutive and 4.68% for downstream introns). Significant differences are also observed beyond the 7(th) nucleotide of the donors. Upstream CpG-rich motifs are not related to Alus, while the latter are frequent in downstream donors. The association of epigenetic modification sites and alternative splicing, indicated above, is not reflected in the computationally obtained splicing potentials.