Microarrays are not the only technology available for high-throughput analysis of gene expression. Serial analysis of gene expression (SAGE) is a technique that involves converting a mixture of cDNA into a linear concatemer of short sequence tags followed by DNA sequencing of the concatemer library (Velculescu et al., 1995). The frequency at which each tag is present in the library represents the abundance of the mRNA transcript from which the tag was derived. SAGE is more technically difficult than microarray analysis and requires a large DNA sequencing capability, but has the advantage that it can detect an entire transcriptome (rather than only genes corresponding to the probes on a microarray chip) as well as changes in the frequency of different splice variants.
SAGE has been used only rarely in aging-related research. In C. elegans, gene expression of long-lived dauer animals relative to controls has been examined by SAGE (Jones et al., 2001), and, more recently, a comparison of gene expression in daf-2 mutants as a function of age has been reported (Halaschek-Wiener et al., 2005). The latter study, in particular, is of interest because a comparison between the SAGE data and analogous microarray data (McElwee et al., 2003; Murphy et al., 2003) has identified a set of six genes, hsp-12.6, vit-2, vit-5, fat-3, nid-1, and mtl-1, that show reproducibly altered expression. SAGE has also been used along with microarray in a comparative analysis of age-correlated changes in muscle gene expression between humans and mice (Welle et al., 2001) and to examine the age-correlated transcriptional changes in the mouse cerebellum (Popesco et al., 2004).
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