Linkage studies in Spanish autosomal dominant polycystic kidney disease-type 2 (ADPKD-2) families

ADPKD results from mutations in at least two genetically distinct loci. Most of the cases (ADPKD-1) are due to mutations in the locus PKD1, on the short arm of chromosome 16. ADPKD-2 accounts for 15% of ADPKD in Spanish population. Previous linkage studies have localized the gene for ADPKD-2 (PKD2) in the chromosome region 4q13-q23, and the distance between the flanking markers, D4S231 and D4S423/D4S414, was 7 cM. We have analyzed seven unrelated families with ADPKD not linked to PKD1 by using eight microsatellite markers that map within the candidate region. All the families did show linkage to any of the markers for which they were informative. Pairwise linkage analysis revealed that loci D4S414 and D4S423 are tightly linked to the disease with lod scores of 3.12 and 6.50, respectively, at a recombination fraction of 0.00. Multilocus linkage analysis indicates that the most likely location for PKD2 is distal to D4S1542, with odds of 1000:1 over the location proximal to D4S1542. Two recombination events involving PKD2 chromosomes have been identified in our seven families. These results provide a proximal boundary for the PKD2 locus and, considering previous studies, its localization is further refined to a 3 cM interval flanked bymore » markers D4S1542 and D4S414/D4S423.« less