Development of Microsatellite Markers for Diagnosis of Autosomal Dominant Polycystic Kidney Disease / 대한신장학회잡지

ABSTRACT

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common hereditary disorder characterized by the slow growth of fluid-filled cysts that distort the renal architecture and lead to a lethal condition. Genetic heterogeneity in ADPKD has been demonstrated after a linkage was initially discovered for PKD1 on chromosome 16p13.3. The second gene, PKD2, has been localized on chromosome 4q21-23 and accounts for approximately 15% of affected families. PKD2 is a -50kb sized gene and has at least 15 exons. PKD2 gene product, polycystin-2, has 968 amino acids and seems to be a transmembrane protein. To find novel microsatellite markers of PKD2, we isolated a PAC DNA containing PKD2 by screening a PAC genomic DNA library. The isolated PAC, PAC47, was restriction-mapped. In addition, a pUC library was constructed by partially digesting PAC47 with Sau3AI. Based on the results of random sequencing of the pUC library, we found several clones that had repeat sequence. By analyzing the polymorphism of these clones, a novel microsatellite marker was discovered that has 0.5945 in HET score. Furthermore, HET score of microsatellite markers neighboring PKD2 was determined in Korean population and then this HET score was compared with that of genome database(GDB). In diagnosis of ADPKD in Korean, these results will improve the efficiency of linkage analysis.