ABERRANT RNA SPLICING OF THE PROTEIN-C AND PROTEIN-S GENES IN HEALTHY-INDIVIDUALS

RNA-based studies are an important tool for the identification and fun ctional characterization of mutations underlying inherited disease. Th ese studies could in principle be compromised by 'aberrant splicing' ( the generation of alternatively spliced transcripts lacking any obviou s function) during normal expression of the genes under investigation. Using a highly sensitive RT-PCR assay, we show here that aberrant spl icing is a frequent occurrence during expression of the protein C (PRO C) and protein S (PROS) genes. Aberrantly spliced transcripts were pre sent in different cell types including liver, the main expressing tiss ue for both protein C and protein S. In an attempt to compare individu al mRNA splicing patterns, PROC and PROS RNA from easily accessible ce lls of different healthy control individuals was studied. However, var iation between different RT-PCR assays from the same individual preclu ded both the relative quantitation of the aberrant transcripts and the analysis of interindividual differences. Our findings are consistent with the notion that a low level of aberrantly spliced transcripts are routinely generated during PROC and PROS gene expression. The possibi lity that these transcripts may complicate the RT-PCR analysis of path ological transcripts must be taken into account when RNA-based strateg ies of disease analysis are considered.