A transcriptional map of the PKD1 locus
- Integrated Genetics, Framingham, MA (United States); and others
Autosomal dominant polycystic kidney disease (ADPKD) is a very common inheritable disease with a frequency of approximately 1 per 1000. While the severity of the disease is variable, 8-10% of the cases clinically proress to end-stage renal disease. The predominant cause of ADPKD, the PKD1 gene, is responsible for about 90% of the cases. The PKD1 gene is located on chromosome 16p13.3 and delimited to an {approximately}750 kb interval defined by the distal marker, D16S84, and the proximal marker, 26.6DIS. This chromosomal segment is known to be contained within a GC-rich isochore, abundant in both CpG-islands and genes. Using filters containing a gridded total human P1 library ({approximately}3 genome equivalents), we have cloned the entire interval as a minimal tiling series of 17 clones. Metaphase FISH has confirmed that each of the clones is solely derived from chromosome 16p13.3 while interphase FISH demonstrated the spatial overlap expected for adjoining P1s. The interval was previously cloned in cosmids with two small gaps (<20 kb) for which we now have cloned DNA. It is not known at this time if the low-copy P1 origin has conferred stability in these previously uncloned segments. We have surveyed the entire PKD1 interval for expressed sequences using 2 mechanistically distinct approaches, direct cDNA selection and exon trapping. The former method utilizes cloned genomic DNA to enrich for cognate cDNAs from complex cDNA mixtures. The latter approach peruses cloned genomic DNA for the presence of biologically functional splice acceptor/splice donor elements. We compare and contrast these transcriptional mapping approaches and present an expressed sequence map of the PKD1 interval.
- OSTI ID:
- 134429
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
Similar Records
Identification of the autosomal dominant polycystic kidney disease gene, PKD1
Mutation analysis of the polycystic kidney disease 1 (PKD1) gene