FINE MAPPING OF THE AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY-DISEASE LOCUS (PKHD1) AND THE GENES MUT, RDS, CSNK2-BETA, AND GSTA1 AT 6P21.1-P12

A total of 33 polymorphic markers were analyzed to generate a high-res olution genetic linkage map of the locus PKHD1 (polycystic kidney and hepatic disease 1) for the autosomal recessive polycystic kidney disea se (ARPKD), using a combination of recombination mapping and linkage a nalysis in 164 families. Recombinants narrowed the PKHD1 region from 3 .8 cM to a 1-cM interval flanked by the markers D6S1024 smd D6S1714, L inkage disequilibrium analysis in 13 Finnish ARPKD families identified two different highly conserved haplo-types with four distal flanking markers, suggesting the existence of at least two major mutations of F innish origin. The genes MUT (methylmalonyl coenzyme A-mutase), RDS (r etinal degeneration, slow), CSNK2 beta (casein kinase II, beta subunit ), and GSTA1 (glutathione S-transferase alpha, type 1) were excluded a s PKHD1 genes casing both established and novel intragenic polymorphis ms in families with key recombinants. These genetic data, combined wit h our YAC-based physical map of the 6p21-p12 region, will facilitate e fforts to positionally clone the PKHD1 gene. (C) 1998 Academic Press.