(Directly taken from the application) Autosomal dominant polycystic kidney disease (APKD) is the most common renal hereditary disease, and accounts for 7-10 percent of renal failure. Incidence of the disorder is approximately 1/1000, making APKD one of the most common genetic diseases. In the summer of 1994, the gene responsible for the majority of APKD, (PKD1) was identified by the European Polycystic Kidney Disease Consortium, opening the door to molecular analyses of this disease. In turn, a better understanding of the pathophysiology of the disease should ultimately lead to improved diagnosis and treatment of the disease. A major goal of the work described in this proposal is to characterize mutations in PKD1, including identification, determination of frequency, genotype-phenotype correlations, and the effect of different mutations on cellular localization of the PKD1 gene product. As part of these studies, we will complete the construction of a full-length cDNA, and generate additional antibodies to various PKD1 protein domains. Together with the complete genomic sequence, expressed transcript(s), and carboxyterminal antibodies that we have previously generated, these reagents will be used to help characterize the different mutations identified in patient samples.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK044853-07
Application #
2518316
Study Section
Special Emphasis Panel (SRC (02))
Project Start
1995-09-30
Project End
1998-08-31
Budget Start
1997-09-30
Budget End
1998-08-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Integrated Genetics, Inc.
Department
Type
DUNS #
City
Framingham
State
MA
Country
United States
Zip Code
01701
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