1. ¹Department of Human Genetics, University of Ulm, Germany
2. ²Gene Mapping Center, Max Delbrueck Center for Molecular Medicine, Berlin, Germany

Correspondence: Dr D Kaufmann, Department of Human Genetics, University of Ulm, Albert Einstein Allee 11, Ulm D 89070, Germany. Tel: +49 731 500 23419; Fax: +49 731 500 23438; E-mail: dieter.kaufmann@medizin.uni-ulm.de

Received 5 March 2003; Revised 25 June 2003; Accepted 29 August 2003; Published online 29 October 2003.

Abstract

It is still not fully understood to what extent intronic sequences contribute to the regulation of the different forms of alternative splicing. We are interested in the regulation of alternative cassette exon events, such as exon inclusion and exon skipping. We investigated these events by comparative genomic analysis of human and mouse in five experimentally well-characterized genes, neurofibromatosis 1 (NF1), cystic fibrosis transmembrane conductance regulator (CFTR), period 3 (PER3), cysteinyl-tRNA synthetase (CARS) and synaptotagmin 7 (SYT7). In NF1, high intron identity around the 52 constitutive and four alternatively skipped NF1 exons is restricted to the close vicinity of the exons. In contrast, we found on average high conservation of intron sequences over 300 base pairs up- and downstream of the five alternatively included NF1 exons. The investigation of alternatively included exons in CFTR, PER3, CARS and SYT7 supported this finding. In contrast, the mean intron identities around the alternatively skipped exons in CTFR and NF1 do not differ considerably from those around the constitutive exons. In these genes, the difference in intron conservation could point to a difference between the regulation of alternative exon inclusion and alternative exon skipping or constitutive exon splicing. Additional genome-wide investigations are necessary to elucidate to what extent our finding can be generalized.