Twinning and mitotic crossing-over: some possibilities and their implications

Mitotic crossing-over does occur in man and is much more frequent and important than generally assumed. Its postzygotic occurrence before an embryo differentiates into MZ twins is theoretically predicted to have disrupting effects on genomic imprinting and cis-acting sequences, with consequences ranging from early lethality to MZ twin discordance. Some predictions are at odds with classical views on twinning and include a high discordance rate of MZ twins for some genetic diseases. A review of MZ twin discordance and an attempt at explaining some of the data lead one to hypothesize both the existence of a sex differences in the rate of mitotic crossing-over and the impossibility for crossed X chromosomes to undergo inactivation. The close interrelationship of twinning and midline malformations further suggests a major role of mitotic crossing-over in the induction of the twinning process itself. The model can be tested with molecular methods and provides a new approach for the gene mapping of so-called multifactorial diseases and of rarer disorders with apparently irregular inheritance.