A YAC, P1, AND COSMID CONTIG AND 17 NEW POLYMORPHIC MARKERS FOR THE WERNER SYNDROME REGION AT 8P12-P21

A yeast artificial chromosome (YAC), P1, and cosmid clone contig was c onstructed for the Werner syndrome (WRN) region of chromosome 8p12-p21 and used to clone a candidate gene for WRN. This region also possibly contains a familial breast cancer locus. The contig was initiated by isolating YACs for the glutathione reductase (GSR) gene and extended i n either direction by walking techniques. Sequence-tagged site (STS) m arkers were generated from subclones of 2 GSR YACs and used to identif y P1 and cosmid clones. Additional STSs were generated from P1 and cos mid clones and from potential expressed sequences identified by cDNA s election and exon amplification methods. The final contig was assemble d by typing 17 YACs, 20 P1 clones, and 109 cosmids for 54 STS markers. The WRN region could be spanned by 2 nonchimeric YACs covering approx imately 1.4 Mb. A P1/cosmid contig was established covering the core 7 00-800 kb of the WRN region, Fifteen new short tandem repeat polymorph isms and 2 biallelic polymorphic markers were identified and included as STSs in the contig. Analysis of these markers in Werner syndrome su bjects demonstrates that the candidate WRN gene is in a region of link age disequilibrium. (C) 1996 Academic Press, Inc.