Abstract

My laboratory is interested in the organization and expression of genes at the end of the long arm of the human X chromosome and their relationship to human disease. We have cloned and characterized a cDNA for the human HPRT gene, and we now plan to characterize the genomic structure of the HPRT gene to determine the nature of the genetic defects in the Lesch-Nyhan syndrome and in gouty arthritis associated with partial HPRT deficiency. We shall characterize flanking sequences by """"""""chromosome walking"""""""" methods, using either lambda genomic clones or the larger cosmid genomic clones already available in our laboratory. Furthermore, we will study the organization of human sequences present in a series of hamster-human hybrid cells known to contain the human HPRT gene together with variable amounts of sequences extending in both directions along the human X chromosome. We also plan to use a variety of other X-linked genes, including those for G6PD, factor VIIIc, and regions associated with fragile X, color blindness and other markers to be mapped to this region. By these methods and by nucleotide sequence determination, we hope to determine the organization of the large portion of the human X chromosome extending from near the HPRT transcription insert to the end of the long arm of the chromosome, and to correlate mutations in this region with a variety of disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028223-06
Application #
3275525
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1980-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1987-07-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Wolff, J A; Yee, J K; Skelly, H F et al. (1987) Expression of retrovirally transduced genes in primary cultures of adult rat hepatocytes. Proc Natl Acad Sci U S A 84:3344-8
Jolly, D J; Yee, J K; Friedmann, T (1987) High-efficiency gene transfer into cells. Methods Enzymol 149:10-25
Yee, J K; Jolly, D J; Miller, A D et al. (1987) Epitope insertion into the human hypoxanthine phosphoribosyltransferase protein and detection of the mutant protein by an anti-peptide antibody. Gene 53:97-104
Wolff, J A; Yee, J K; Skelly, H et al. (1987) Adult mammalian hepatocyte as target cell for retroviral gene transfer: a model for gene therapy. Somat Cell Mol Genet 13:423-8
Yee, J K; Moores, J C; Jolly, D J et al. (1987) Gene expression from transcriptionally disabled retroviral vectors. Proc Natl Acad Sci U S A 84:5197-201
Kim, S H; Moores, J C; David, D et al. (1986) The organization of the human HPRT gene. Nucleic Acids Res 14:3103-18
Yee, J K; Jolly, D J; Moores, J C et al. (1986) Gene expression from a transcriptionally disabled retroviral vector. Cold Spring Harb Symp Quant Biol 51 Pt 2:1021-6
Jolly, D J; Willis, R C; Friedmann, T (1986) Variable stability of a selectable provirus after retroviral vector gene transfer into human cells. Mol Cell Biol 6:1141-7
Koenker, R; Luchtman, L A; Willis, R C et al. (1986) The biochemical mechanism of metabolic cooperation. Adv Exp Med Biol 195 Pt A:183-7
Gruber, H E; Finley, K D; Luchtman, L A et al. (1986) Insertion of hypoxanthine phosphoribosyltransferase cDNA into human bone marrow cells by a retrovirus. Adv Exp Med Biol 195 Pt A:171-5

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