Projects / Programmes
Screening for mutations in the PKD1 gene and identification of modifying changes that cause early onset disease
| Code |
Science |
Field |
Subfield |
| 3.05.00 |
Medical sciences |
Human reproduction |
|
| Code |
Science |
Field |
| B790 |
Biomedical sciences |
Clinical genetics |
PKD1, mutations, early onset, genetic modifyers, ADPKD
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
13412 |
PhD Lana Strmecki |
Biochemistry and molecular biology |
Head |
1999 - 2000 |
36 |
Organisations (1)
Abstract
Nutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder (frequency of 1 in 1000) characterised by progressive renal cyst development leading to end stage renal disease. ADPKD exhibits marked phenotypic variability ranging from rare cases of early onset disease to individuals with adequate renal function in old age. Genomic duplication of the major ADPKD locus, PKD1, has complicated mutation detection and prevented a screen of the entire gene. Only one third of the gene can be analysed using classical mutation detection methods. We propose to develop a strategy to amplify each PKD1 exon specifically, exploiting rare sequence difference with the homologous loci, and screen for mutation by direct sequencing. One hundred PKD1 patients will be analysed to determine the mutational spectrum in a single population. In addition, 34 early onset families will be examined and their mutations compared to typical cases.
Previous studies have suggested that modifying factors influence the severity of disease in ADPK. We plan to look for potential modifying changes in candidate genes by sequence analysis of the early onset patients. Loci that will be studied are the PKD1 allele inherited from the normal parent (preliminary evidence suggest that this may be important) as well as a second ADPKD locus, PKD2 and the reccessive PKD gene. The identification of important modifiers to ADPKD will be of deagnostic/prognostic importance and may also help us to understand the mutational mechanism in ADPKD.
