Are monozygotic twins discordant for psychosis caused by differential methylation?

It is known that certain somatic mutations occurring simultaneously with, or after, twinning may cause phenotypic differences between monozygotic twins (MZT). Thus, we hypothesized that cases of MZT discordant for schizophrenia might also be caused by unknown genomic discordance. Genomic differences were detected by using a new technique, restriction landmark genome scanning (RLGS). A detailed comparison of the RLGS patterns detected at least five spots (spots 1-5) showed obviously different autoradiographic intensities between the twins. After trying to clone fragments that produced all the spots, we obtained four clones. Two alternative mechanisms by which the discrepant fragments appear in the twins are possible. First, in either of the twins, a submicroscopic change of DNA, for example, deletion/insertion, substitution, or translocation, may have occurred at NotI-flanking sites simultaneously with, or after, twinning. Second, as we used the methylation-sensitive enzyme, NotI, the methylation status at NotI site(s) may be different between the twins. I think that this possibility might have great significance. If, in this new strategy, differences of transcription level of one or more genes between the twins are shown, this will contribute to a search for the pathogenesis of schizophrenia.