Functional analysis of synonymous substitutions predicted to affect splicing of the CFTR gene.

ABSTRACT:

Background

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Over 1800 CFTR mutations have been reported, and about 12% of mutations are believed to impair pre-mRNA splicing. Given that several synthetic, non-splice-junction synonymous substitutions have been reported to alter splicing in CFTR, we predicted that naturally occurring synonymous substitutions may be erroneously classified as functionally neutral.

Methods

Computational tools were used to predict the effect of synonymous substitutions on CFTR pre-mRNA splicing. The functional consequences of selected substitutions were evaluated using a minigene splicing assay.

Results

Two synonymous mutations were shown to have a dramatic effect on CFTR pre-mRNA

SUBMITTER: Scott A 

PROVIDER: S-EPMC3440543 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature