The research outlined in this proposal is designed to enhance our understanding of the structure and functional organization of the human sex chromosomes. The experiments described should clarify the evolutionary origins of the X and Y chromosomes, and aspect of their role in sex determination. The regulation of gene expression on the X and Y through th process of X inactivation will be studied which should provide insight into general mechanisms involved in the control of development and may help clarify the pathogenesis of sex chromosome aneuploid disorders such as the Turner syndrome and the Klinefelter syndrome. Detailed mapping of this region will contribute to the goals of the human genome initiative. A grou of promoter sequences which escape inactivation will be characterized and the information derived may be of use in designing vectors for gene therap experiments. Finally, the mechanisms which produce frequent deletions of DNA from the X chromosome will be explored. These studies should provide insight into the cause of deletions in such human disorders as X-linked ichthyosis, thalassemia, and muscular dystrophy
| Alperin, E S; Shapiro, L J (1997) Characterization of point mutations in patients with X-linked ichthyosis. Effects on the structure and function of the steroid sulfatase protein. J Biol Chem 272:20756-63 |
