Abstract

The proposed research is designed to increase our understanding of human X-chromosome inactivation. Specifically we plan to investigate whether X-inactivation is modified in structurally abnormal X chromosomes so that loci such as steroid sulfatase (STS) which escape X-inactivation on structurally normal human inactive X's, undergo inactivation when present on a structurally abnormal inactive X. Mouse-human hybrids containing structurally abnormal inactive human X chromosomes will be isolated and evaluated for the expression of human STS. Secondly, we wish to investigate whether the inactive X in huma cells derived from trophectoderm is maintained in the inactive state by a DNA modification mechanism, as appears to be the case in somatic cells. In order to test this, transformation studies will be performed using DNA isolated from human chorionic villi obtained from abortus material. Thirdly, we wish to map the chromosomal location of the STS locus in mouse using somatic cell hybrids segregating mouse chromosomes. The long-term goal of this research is to elucidate the mechanism of X-chromosome inactivation. Since sex-linked diseases and X chromosome aneuploid states make up a substantial portion of the human genetic disease burden, the results of these studies will have practical importance. In addition, these investigations should provide useful information regarding control of gene expression with attendant implications for developmental biology, and neoplastic cell growth.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015193-05
Application #
3312992
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1981-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Los Angeles County Harbor-UCLA Medical Center
Department
Type
DUNS #
City
Torrance
State
CA
Country
United States
Zip Code
90509

  Publications

Glass, I A; Passage, M; Bernatowicz, L et al. (1996) Generation of sequence-tagged sites from Xp22.3 by isolating common Alu-PCR products of radiation hybrids retaining overlapping human X chromosome fragments. Hum Genet 97:604-10
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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