ANALYSIS OF THE GENOMIC SEQUENCE FOR THE AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE (PKD1) GENE PREDICTS THE PRESENCE OF A LEUCINE-RICH REPEAT

The complete genomic sequence of the gene responsible for the predomin ant form of polycystic kidney disease, PKD1, was determined to provide a framework for understanding the biology and evolution of the gene, and to aid in the development of molecular diagnostics. The DNA sequen ce of a 54 kb interval immediately upstream of the poly(A) addition si gnal sequence of the PKD1 transcript was determined, and then analyzed using computer methods. A leucine-rich repeat (LRR) motif was identif ied within the resulting predicted protein sequence of the PKD1 gene. By analogy with other LRR-containing proteins, this may explain some o f the disease-related renal alterations such as mislocalization of mem brane protein constituents and changes in the extracellular matrix org anization. Finally, comparison of the genomic sequence and the publish ed partial cDNA sequence showed several differences between the two se quences. The most significant difference detected predicts a novel car boxy-terminus for the PKD1 gene product.