Twin data in support of the lyon hypothesis

THE Lyon hypothesis1,2 suggests that in the XX mouse and human female one X chromosome is genetically inactive after a certain stage in embryogenesis; that this ‘inactive’ X chromosome forms the Barr body, which can be identified at about the sixteenth day in the human embryo; that it is a random proposition which of the two X chromosomes in a given cell becomes the genetically inactive one; that once it is decided which X chromosome is to be the genetically inactive one in a given cell all descendants of this cell abide by the decision and have the same X chromosome inactive; and that the germ cell line does not participate in this process of X chromosome differentiation. The hypothesis suggests a mechanism: (1) of dosage compensation for the ‘excess’ genetic material in females; (2) of the observed phenotypic variability in females heterozygous for X-borne recessive mutations. The hypothesis requires the existence, in heterozygous females, of two populations of cells with regard to a particular trait for which the female is heterozygous. Beutler3 seems to have indirect evidence for such, in females heterozygous for glucose-6-phosphate dehydrogenase deficiency. All the genetic and cytological evidence supporting this attractive hypothesis1–4 will not be reviewed here. Some further evidence in its support will, however, be presented.