Search for a genetic event in monozygotic twins discordant for schizophrenia

When monozygotic twins are discordant for the diagnosis of schizophrenia, this discordance has been traditionally attributed to environmental factors acting upon a genome susceptible for the schizophrenia phenotype. The study presented here was designed to examine the occurrence of a genetic event, such as a postzygotic mitotic crossover, that could account for the discordance. Such a postzygotic event could affect cis-acting sequences and result in a phenotype of variable severity. We used molecular genetic methods to evaluate such an event with 94 microsatellite repeat polymorphic markers distributed on all autosomes and the X chromosome in five pairs of monozygotic twins discordant for schizophrenia. In this search, no genetic marker discordances were identified between the co-twins. The lack of a genetic difference may implicate nongenetic factors that are responsible in eliciting or suppressing the phenotype. However, the experiments performed in this study cannot eliminate the possibility that a tissue-specific mitotic crossover might have occurred in one of the discordant twins, which could not have been detected in our current study.