Abstract

Autosomal dominant polycystic kidney disease has an incidence of approximately 1/1000, and accounts for approximately 10% of end-stage reanl disease. While the basic defect causing one form of APKD, has eluded biochemical and physiological detection, there has been substantial progress in mapping the PKD-1 gene. Isolation of the gene and characterization of the basic defect(s) would lead to better understanding of the etiology and pathogenesis of the disease. The long-term goal of this project is to clone and characterize the PKD-1 gene, and its product. To this end, we will use a highly efficient method of scanning genomic DNA from the interval around PKD-1 for expressed sequences. Expressed sequences recovered by exon trapping will be analyzed by genetic and molecular methods for the presence of the PKD-1 gene. Candidate clones will be analyzed by comparative sequence analysis from normal and affected individuals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK044853-04
Application #
2144115
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1991-09-30
Project End
1995-08-31
Budget Start
1994-09-30
Budget End
1995-08-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Integrated Genetics, Inc.
Department
Type
DUNS #
City
Framingham
State
MA
Country
United States
Zip Code
01701

  Publications

Connors, T D; Burn, T C; VanRaay, T et al. (1997) Evaluation of DNA sequencing ambiguities using tetramethylammonium chloride hybridization conditions. Biotechniques 22:1088-90
Connors, T D; Van Raay, T J; Petry, L R et al. (1997) The cloning of a human ABC gene (ABC3) mapping to chromosome 16p13.3. Genomics 39:231-4
Van Raay, T J; Foskett, S M; Connors, T D et al. (1997) The NTN2L gene encoding a novel human netrin maps to the autosomal dominant polycystic kidney disease region on chromosome 16p13.3. Genomics 41:279-82
Burn, T C; Connors, T D; Van Raay, T J et al. (1996) Generation of a transcriptional map for a 700-kb region surrounding the polycystic kidney disease type 1 (PKD1) and tuberous sclerosis type 2 (TSC2) disease genes on human chromosome 16p3.3. Genome Res 6:525-37
Van Raay, T J; Burn, T C; Connors, T D et al. (1996) A 2.5 kb polypyrimidine tract in the PKD1 gene contains at least 23 H-DNA-forming sequences. Microb Comp Genomics 1:317-27
Van Raay, T J; Connors, T D; Klinger, K W et al. (1996) A novel ribosomal protein L3-like gene (RPL3L) maps to the autosomal dominant polycystic kidney disease gene region. Genomics 37:172-6
Dackowski, W R; Connors, T D; Bowe, A E et al. (1996) The region surrounding the PKD1 gene: a 700-kb P1 contig from a YAC-deficient interval. Genome Res 6:515-24
Burn, T C; Connors, T D; Klinger, K W et al. (1995) Increased exon-trapping efficiency through modifications to the pSPL3 splicing vector. Gene 161:183-7
Burn, T C; Connors, T D; Dackowski, W R et al. (1995) Analysis of the genomic sequence for the autosomal dominant polycystic kidney disease (PKD1) gene predicts the presence of a leucine-rich repeat. The American PKD1 Consortium (APKD1 Consortium). Hum Mol Genet 4:575-82