Refinement of the gene locus for autosomal dominant medullary cystic kidney disease type 1 (MCKD1) and construction of a physical and partial transcriptional map of the region

Autosomal dominant medullary cystic kidney disease (MCKD) is an adult onset tubulointerstitial nephropathy that leads to salt wasting and end-stage re nal failure. A gene locus (MCKD1) has been mapped on chromosome 1q21, Here we report on a large MCKD1 family of British origin linked to the MCKD1 loc us. Haplotype analysis performed with markers spanning the previously repor ted critical MCKD1 region allowed for the refinement of this interval to 4 cM by definition of D1S305 as a new proximal flanking marker. Furthermore, we constructed a yeast artificial chromosome, Pi-related artificial chromos ome, and bacterial artificial chromosome contig of this reson, which is onl y sparsely covered by the Human Genome Sequencing Project. This enabled us to map numerous expressed sequence tags within the critical interval. This physical and partial transcriptional map of the MCKD1 region is a powerful tool for the identification of positional and functional candidate genes fo r MCKD1 and will help to identify the disease-causing gene. (C) 2001 Academ ic Press.