As part of an effort to identify the gene responsible for the predominant form 
of polycystic kidney disease (PKD1), we used a gridded human P1 library for 
contig assembly. The interval of interest, a 700-kb segment on chromosome 
16p13.3, can be physically delineated by the genetic markers D16S125 and D16S84 
and chromosomally characterized as a GC-rich isochore enriched for CpG islands, 
genes, and Alu-like repeats. Our attempts to recover CEPH YACs that encode this 
region of chromosome 16 were unsuccessful. However, we screened an arrayed P1 
library using 15 distinct probes from the D16S125-D16S84 interval and identified 
56 independent P1 clones. Only one probe from the interval was unsuccessful in 
identifying a P1 clone. Forty-four P1 clones were determined to be unique based 
on restriction enzyme analysis, and 42 of these were found to originate from 
chromosome 16p13.3, based on FISH to metaphase chromosomes. The 700-kb interval 
could be defined by a single sequence-ready contig comprised of 12 P1 clones and 
1 cosmid clone. Our studies support the use of multiple libraries to generate 
the requisite physical reagents for positional cloning and encourage the use of 
Escherichia coli-based large-insert cloning systems to recover clones from 
YAC-deficient chromosomal intervals.