GeneSplicer: a new computational method for splice site
prediction" Nucleic Acids Res 29: 11851190 (2001)
Section 3 introduces the basic knowledge about splice site
and describes the method and process of our approach.
578_579 + 5delAAGTATG [710_711 + 5del7] deletion that spans an exonic splice site
causes a frameshift and could affect splicing at the same time.
This indicates that small changes in a nucleotide sequence near a splice point can lead to large changes in splice site
choice and proteins produced.
On the other hand, our results obtained with splicing-prediction tools show that 1 of the 30 sequence variants we detected (rs7252245) lies within a predicted splice site
(see Table 1 in the online Data Supplement).
We used 4 splice site
analysis tools to predict the effect on splicing, with conflicting results (Table 1).
Following this step-by-step filtering protocol, only one novel DFNA5 splice site
mutation, IVS8+1 delG, was likely to be pathogenic according to this criterion [Figure 3] and [Figure 4]a.
These mutations were considered putative disease-causing mutations on the basis of a finding that (a) the affected amino acid was conserved during evolution or (b) a splice site
was either created or abolished.
This mutation, which was previously described in individuals of Moroccan origin (7), occurs 23 positions downstream from the 5' splice site
in a tract that, compared with the other junctions, does not contain conserved sequence elements.
Alternatively the mutation at the ultimate nucleotide of exon 9 could affect splicing at the adjacent intron 9 donor splice site
, with various potential splicing outcomes (Fig.
The [alpha] splice site
causes a 36-bp deletion within the conserved reverse transcriptase motif A (16) and was found to be a dominant negative inhibitor of telomerase activity (21).
Alternative splicing by a cryptic acceptor splice site
in exon 9 restores the normal reading frame disrupted by the mutation and eliminates the stop codon.