Linkage Analysis of Autosomal Dominant Polycystic Kidney Disease in Iranian Families through PKD1 and PKD2 DNA Microsatellite Markers

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous disorder. Two known loci, including PKD1 (16p13.3) and PKD2 (4q21), as well as a third locus that is not clearly identified, cause ADPKD. Objectives: The aim of this study was to assess the genetic linkage of 4 linked microsatellite markers of PKD genes (PKD1 and PKD2) to ADPKD for genetic screening of familiar PKD patients in Yazd. Methods: This familial case-control study was conducted among 18 families. The linkage analysis was performed using 2 pairs of polymorphic microsatellite markers that are closely linked to the PKD1 gene (16AC2.5 and KG8) and 2 other pairs closely linked to the PKD2 gene (D4S231 and D4S423). These markers were detected through PCR of tandem repeats method and polyacrylamide gel electrophoresis. Results: The disease was linked to PKD1 about 77.8%, PKD2 16.7% of the families, and to neither gene in 5.5%, according to LOD scores and allele segregation analysis. It also found relatively high heterozygosity and polymorphism information contents (PIC) values for 3 markers including 16AC2.5 (PIC: 0.798) for PKD1 gene and D4S423 (PIC: 0.807) as well as D4S231 (PIC: 0.741) for PKD2 gene. However, it seems that KG8 marker has no significant linkage to the PKD1 gene (PIC: 0.329) among Yazd PKD patients. Conclusions: These results show similarity to another report from Iranian families and according to these similar results, it seems that 16AC2.5 and D4S423 markers would provide an improved framework for genetic screening of ADPKD patients among familiar PKD patients in Yazd.