Genetics of disease. The sex chromosomes and human disease

Mammalian sex chromosomes display significant differences from autosomes in both structure and function. The involvement of the Y in sex determination and fertility; the need for correct pairing and segregation of two grossly different chromosomes during male meiosis; the ability to dosage compensate X-linked genes by epigenetic means; the viability of sex chromosome aneuploidies; and the different consequences of mutations in X-linked genes in males and females as a result of the mosaic nature of mammalian females: these are just some of the unique properties that evolution has donated to our sex chromosomes. This special issue of Current Opinion of Genetics & Development focuses on recent findings on sex chromosome organization and evolution, on X chromosome inactivation and on diseases caused by sex chromosome abnormalities. The emerging picture is one in which each of the above-mentioned features reveal a considerable number of exceptions (see Table 1), suggesting that in our evolutionary history the presence of heteromorphic sex chromosomes might represent a transition phase to which we are still trying to adjust.