Examples of tissue-specific AS events in human genes with evidence of splice conservation in orthologous mouse genes. (a) Human fragile X mental retardation syndrome-related (FXR1) gene splicing detected in brain-derived EST sequences. FXR1 exhibited two alternative mRNA isoforms differing by skipping/inclusion of exons E15 and E16. Exclusion of E16 creates a shift in the reading-frame, which is predicted to result in an altered and shorter carboxy terminus. The exon-skipping event is conserved in the mouse ortholog of the human FXR1 gene, and both isoforms were detected in mouse brain-derived ESTs. (b) Human betaine-homocysteine S-methyltransferase (BHMT) gene splicing detected in liver-derived ESTs. BHMT exhibited two alternative isoforms differing by alternative 5' splice site usage in exon E4. Sequence comparisons indicate that the exon and splice site sequences involved in both alternative 5' splice site exon events are conserved in the mouse ortholog of the human BHMT gene. (c) Human cytochrome P450 2C8 (CYP2C8) gene splicing. CYP2C8 exhibited two alternative mRNA isoforms differing in the 3' splice site usage for exon E4 (detected in ESTs derived from several tissues), where the exclusion of a 71-base sequence creates a premature termination codon in exon E4b. Exons and splice sites involved in the AS event are conserved in the mouse ortholog of CYP2C8.