Comparison of Methods for Identifying Transcription Units and Transcription Map of the Werner Syndrome Gene Region

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To isolate a human disease gene by positional cloning, a critical step is the identification of candidate genes from a targeted genomic region. We used cDNA selection, exon trapping, and genomic sequencing to identify 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 of a positional cloning effort. The result of this combined method was significant overlap among the transcription units identified by each method; yet, no one method identified all of the transcription units. We present here a comparison of the effectiveness and efficiency of these methods and present a transcription map of the Werner syndrome gene region.