Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

ABSTRACT: Despite a growing number of splicing mutations found in hereditary diseases, utilization of aberrant splice sites and their effects on gene expression remain challenging to predict. We compiled sequences of 346 aberrant 5'splice sites (5'ss) that were activated by mutations in 166 human disease genes. Mutations within the 5'ss consensus accounted for 254 cryptic 5'ss and mutations elsewhere activated 92 de novo 5'ss. Point mutations leading to cryptic 5'ss activation were most common in the first intron nucleotide, followed by the fifth nucleotide. Substitutions at position +5 were exclusively G>A transitions, which was largely attributable to high mutability rates of C/G>T/A. However, the frequency of point mutations at position +5 was significantly higher than that observed in the Human

SUBMITTER: Buratti E 

PROVIDER: S-EPMC1934990 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature