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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015193-09
Application #
3312995
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1981-08-01
Project End
1992-03-31
Budget Start
1989-12-01
Budget End
1992-03-31
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
City
Torrance
State
CA
Country
United States
Zip Code
90502
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Wu, J; Ellison, J; Salido, E et al. (1994) Isolation and characterization of XE169, a novel human gene that escapes X-inactivation. Hum Mol Genet 3:153-60
Salido, E C; Passage, M B; Yen, P H et al. (1993) An evaluation of the inactive mouse X chromosome in somatic cell hybrids. Somat Cell Mol Genet 19:65-71
Ellison, J; Passage, M; Yu, L C et al. (1992) Directed isolation of human genes that escape X inactivation. Somat Cell Mol Genet 18:259-68
Wang, J C; Passage, M B; Ellison, J et al. (1992) Physical mapping of loci in the distal half of the short arm of the human X chromosome: implications for the spreading of X-chromosome inactivation. Somat Cell Mol Genet 18:195-200
Bernatowicz, L F; Li, X M; Carrozzo, R et al. (1992) Sequence analysis of a partial deletion of the human steroid sulfatase gene reveals 3 bp of homology at deletion breakpoints. Genomics 13:892-3
Yen, P H; Ellison, J; Salido, E C et al. (1992) Isolation of a new gene from the distal short arm of the human X chromosome that escapes X-inactivation. Hum Mol Genet 1:47-52
Ellison, J W; Ramos, C; Yen, P H et al. (1992) Structure and expression of the human pseudoautosomal gene XE7. Hum Mol Genet 1:691-6
Mohandas, T K; Speed, R M; Passage, M B et al. (1992) Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: meiotic studies in a man with a deletion of distal Xp. Am J Hum Genet 51:526-33
Yen, P H; Tsai, S P; Wenger, S L et al. (1991) X/Y translocations resulting from recombination between homologous sequences on Xp and Yq. Proc Natl Acad Sci U S A 88:8944-8

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