Long term objectives of this research is to further our understanding of the organization and function of the human X chromosome employing a combination of somatic cell, cytogenetic and molecular techniques. In studies proposed here efforts will be focused on the genetics of the distal end of the short arm of the X chromosome using a number of molecules probes, including a newly isolated cDNA clone for the enzyme steroid sulfatase (STS). Functional sequences for STS are located at the distal end of the short arm of human X and escape X- inactivation. Nonfunctional STS-related sequences on the Y are located on its long arm. We wish to further characterize the molecular nature of X-Y pairing and its role in the origin of XX males, XY females and individuals with STS deficiency. Mouse- human cell hybrids will be constructed from the fusion of cells from individuals with these genetic conditions to separate their sex chromosomes. DNA of individual X or Y chromosomes will then be evaluated with a number of probes located at the distal ends of the short arm of these chromosomes. The involvement of functional STS sequences in the X-Y interchange leading to the rare genetic conditions of XX males and XY females will be determined. Also, we propose to evaluate the role of X-Y interchange in a more common condition of STS deficiency. Distal ends of the short arms of the human X and Y chromosomes are of particular interest from a genetic standpoint because (a) they pair and undergo genetic exchange during meiosis, and (b) genes in this region on the X escape the usual X inactivation and testicular determining factor(s) are located in proximity to this region on the Y. The studies proposed here will further elucidate the nature of X-Y pairing and exchange and its role in the origin of genetic diseases.
Showing the most recent 10 out of 15 publications
