Identification of the autosomal dominant polycystic kidney disease gene, PKD1
- Harvard Medical School, Boston, MA (United States); and others
The PKDl gene was localized to an {approximately}480 kb interval of chromosome 16pl3. More than 20 independent transcripts were found in the interval. In view of the high new mutation rate in autosomal dominant polycystic kidney diseases (ADPKD), we anticipated the PKD1 gene would be large. The largest transcript in the region was represented by five cDNA clones located adjacent to the tuberin gene (TSC2). Two of these clones, KG8 and NKG9, contain {approximately}4.5 kb of contiguous sequence corresponding to the 3{prime} end of the 14 kb mRNA which is transcribed from telomeric to centromeric. They spans 11 exons, and to evaluate the reading frame of the cDNA, we have compared the human and monkey sequence using human primers, and found 90-94% identity at the DNA level, and by observing amino acid conservation, determined the reading frame. To date, our open-reading frame of {approximately}800 amino-acids contained only a potential threonine kinase site, but no other recognizable peptide motifs or repeats, and was not homologous to sequences in Swissprot and GenBank. No Southern blot abnormalities have been detected with the cDNA probes used. However, an exon-by-exon scan of 8 exons for mutations by SSCP and genomic sequencing (predicted missense changes) has identified 3 patients with mutations not found in normals, and identify the KG8 gene as the PKD1 gene.
- OSTI ID:
- 133311
- 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
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