Better Gel Resolution and Longer cDNAs Increase the Precision of Differential Display

become a widely used method for the rapid identification of differentially expressed genes in a variety of eukaryotic systems (4). In the past three years, technical modifications have reduced the redundancy of anchored primers, decreased the number of reverse transcription reactions needed, increased reproducibility, reduced the incidence of false positives and increased the overall efficiency of the method (5). The original method separates cDNAs on a denaturing polyacrylamide gel. However, conventional DNA sequencers sometimes do not provide adequate gel resolution, resulting in the inadvertent isolation of several cDNAs from what appears to be a single band. These cDNAs may represent independent cDNA fragments of the same or very similar molecular weight (2), separated strands of a unique doublestranded cDNA molecule with or without Taq DNA polymerase-mediated addition of 3′-terminal adenosine nucleotide (1), truncated polymerase chain reaction (PCR) products of a unique cDNA (unpublished data) and fragments representing a unique cDNA with multiple polyadenylation sites (3). Here we report the use of a new programmable DNA sequencer, called the GenomyxLR (Genomyx, Foster City,