Linkage exclusion between the autosomal dominant polycystic kidney disease locus and chromosome 16 markers in a new family

Abstract

A family segregating for autosomal dominant polycystic kidney disease (ADPKD) is reported. The clinical picture was typical for ADPKD in some family members, although others showed mild involvement. DNA from family members was probed with seven chromosome 16 single-copy DNA sequences that mapped to the telomere of the short arm of the chromosome. The most likely order of six of the probes from the telomere is palpha3'HVR.64 at the designated locus D16S85, CRI-0327 at D16S63, CRI-090 at D16S45, CRI-0129 at D16S56, CRI-0133 at D16S58, and CRI-0136 at D16S60, with the PKD1 locus for ADPKD between D16S85 and D16S63. The seventh probe 24-1 at D16S80 had not been ordered in relation to the other sequences, but PKD1 had been mapped between it and D16S85. The three probes that were informative in our family, palpha3'HVR.64, CRI-090, and CRI-0136 had been linked to the disease locus at recombination frequencies of 4% and approximately 6 and 12%, respectively. Linkage was excluded between the ADPKD locus in our family and palpha3'HVR.64 at a recombination value of up to 6%. Linkage was also excluded between CRI-090 and the disease locus at a recombination value of up to 5%. The data for linkage between CRI-0136 and the ADPKD locus in our family were inconclusive. Multipoint analysis excluded the possibility that the disease in this family lies between the flanking genetic markers that have previously been used to define the genetic interval in which the most common form of polycystic kidney disease, PKD1, lies. We have not made a positive assignment of the ADPKD mutation in this family.(ABSTRACT TRUNCATED AT 250 WORDS)