Background: Alternative splicing is a mechanism for increasing protein diversity by excluding or including exons during post-transcriptional processing. Alternatively spliced proteins are particularly relevant in oncology since they may contribute to the etiology of cancer, provide selective drug targets, or serve as a marker set for cancer diagnosis. While conventional identification of splice variants generally targets individual genes, we present here a new exon-centric array (GeneChip Human Exon 1.0 ST) that allows genome-wide identification of differential splice variation, and concurrently provides a flexible and inclusive analysis of gene expression.

We measured daily gene expression in heads of control and period mutant Drosophila by using oligonucleotide microarrays. In control flies, 72 genes showed diurnal rhythms in light-dark cycles; 22 of these also oscillated in free-running conditions. The period gene significantly influenced the expression levels of over 600 nonoscillating transcripts. Expression levels of several hundred genes also differed significantly between control flies kept in light-dark versus constant darkness but differed minimally between per 01 flies kept in the same two conditions. Thus, the period-dependent circadian clock regulates only a limited set of rhythmically expressed transcripts. Unexpectedly, period regulates basal and light-regulated gene expression to a very broad extent.F orward genetic screens in Drosophila melanogaster have identified at least eight genes [period (per), timeless (tim), cycle (cyc), clock (Clk), vrille (vri), doubletime, cryptochrome (cry), and shaggy] necessary for the normal functioning of the circadian time-keeping system. Null mutations in most of these genes render flies behaviorally arrhythmic in constant conditions, but they otherwise have minimal morphologic phenotype (1). A model for the mechanism by which specific gene products give rise to a stable clock mechanism has been formulated over the past 10 years (2, 3). These clock genes appear to function in a time-delayed transcription-translation feedback loop. A rhythmically expressed subset of the core clock genes (per, tim, and Clk) and a nonrhythmically expressed core clock gene (cyc) are thought to function as the state variables of the oscillator mechanism (4). This model predicts that these core clock genes also should influence the rhythmic expression of ''output'' genes important in regulating physiologic and biologic processes controlled by the circadian clock (5).Previous screens for such clock-controlled output genes have yielded varying estimates of their abundance and character in different organisms. An insertional reporter screen in the photosynthetic prokaryote Synechococcus suggested that most genes in this organism are transcribed in circadian fashion (6). Using microarray analysis, Harmer et al. identified 453 genes undergoing rhythmic expression under constant conditions in the plant Arabidopsis thaliana (7), representing Ϸ6% of the expressed genome. In Drosophila, analysis of 280 expressed sequence tags from the fly head revealed 20 diurnally varying transcripts, the majority of which were extremely rare, long messages of unclear physiologic function (8). The full extent of circadian gene expression is not known in any organism. The recent availability of an oligonucleotide-based microarray containing probes for nearly all known and predicted Drosophila genes allows estimation of the number of clock-controlled genes in the fly. Here we describe results of measuring circadian gene expression in control and period mutant flies in both light-dark (LD) and freerunning conditions. While this article was in preparation, three ot...

ACE inhibition after MI inhibits cardiac hypertrophy, preserves cardiac function, and attenuates changes in myocardial gene expression. Gene expression profiling reveals, however, that some elements of the pathophysiology may be unaffected by the treatment and be targets for new therapies.