Dosage compensation of the X chromosome and Turner syndrome

Turner patients have a karyotype of 45,X, while normal females are 46,XX and normal males are 46,XY. In order to understand Turner syndrome, it is important to understand how gene dosage of the X chromosome is regulated. In this review, we address sex chromosome evolution and the two forms of X chromosome dosage compensation: X upregulation and X inactivation. Recent microarray analyses have provided evidence for two-fold X upregulation in males and females. This equalizes gene dosage between the X chromosome and the autosomes. Inactivation of one of the two X chromosomes in females occurs to prevent functional tetrasomy and to equalize gene dosage between the sexes. However, 15–25% of human X-linked genes escape X inactivation. These escape genes are thought to contribute to the phenotype of Turner patients. Expression of escape genes is tissue-specific, suggesting that their role in Turner phenotypes is tissue-dependent. Recent data support a role for CTCF and chromatin structure in the regulation of genes that escape X inactivation.