COMPARISON OF METHODS FOR IDENTIFYING TRANSCRIPTION UNITS AND TRANSCRIPTION MAP OF THE WERNER-SYNDROME GENE REGION

To isolate a human disease gene by positional cloning, a critical step is the identification of candidate genes from a targeted genomic regi on, We used cDNA selection, exon trapping, and genomic sequencing to i dentify 12 transcription units from a 1.4-Mb genomic region containing the Werner syndrome gene (WRN). This included sequencing of 650 kb in the region of the WRN gene, to date, the most DNA sequenced as part o f a positional cloning effort. The result of this combined method was significant overlap among the transcription units identified by each m ethod; yet, no one method identified all of the transcription units. W e present here a comparison of the effectiveness and efficiency of the se methods and present a transcription map of the Werner syndrome gene region. (C) 1998 Academic Press.