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Appraisal of genetic and epigenetic congruity of a monozygotic twin pair discordant for schizophrenia

The origin of monozygotic (MZ) twins is attributed to two or more daughter cells of a single zygote undergoing independent mitotic divisions, leading to independent development and births. It provides the foundation for the assumption that the resulting twins will be genetically identical. This assumption has been used to evaluate the relative role of genes and environment for a variety of multifactorial features and diseases, including schizophrenia.1 The interpretation of such results, however, has invariably involved controversy, questioning a number of basic assumptions about intrauterine environment and genetic identity of twins, among others.

In this context, although differences in the placenta, amniotic sac, and vascularisation of separate cell masses can lead to discordance,2 it is difficult to establish it experimentally.3 On the other hand, it has been possible to assess to a limited degree the genetic identity of MZ twins, using cytogenetic and genetic technologies. The results have allowed Hall and Lopez-Rangel4 and others to suggest the involvement of mosaicism in causing discordance between MZ twins. Interestingly, karyotype discordance between monozygotic twins has been reported in a number of genetic syndromes. These include Ulrich-Turner syndrome,5 Duchenne muscular dystrophy,6 and Turner syndrome.7 Molecular differences between rare monozygotic twins have also been reported with respect to telomere length,8 loss of heterozygosity mutations,9 triplet repeat expansion,10 gene expression,4 HERV11 and HTLV-112 repeat sequences among others. Although such reports suggest possible genomic discordance between the MZ twins, the question remains as to whether they represent an exception or the rule across MZ twin pairs. Also, is genomic discordance a common feature of every pair of monozygotic twins or is it restricted to a few rare cases only? Determination of whether a pair of MZ twins is truly genetically identical would involve …