Figure 4.

MZ twins as a model for assessing the genetic threshold liability hypothesis. Representation of three sets of twins [MZC well (monozygotic twins both unaffected), MZC disease (monozygotic twins both diseased) and MZD (monozygotic twins discordant)] within the threshold liability hypothesis (unaffected = blue, disease affected = red). In this model, the affected twin in the MZD pair must acquire somatic mutation/epimutation to cross the threshold and develop the disease. Genomic and epigenomic assessment of these exceptional twin pairs will allow for identification of pair-specific postzygotic somatic event(s) [Adapted from Castellani et al. (88, 89)].