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Background  Alternative Promoter (AP) usages have been shown to enable diversified transcriptional regulation of individual gene in a context-specific (e.g., pathway, cell lineage, tissue type, and development stage  et. ac. ) way. Aberrant uses of APs have been directly linked to mechanism of certain human diseases. However, whether or not there exists a general link between a gene's AP repertoire and its expression diversity is currently unknown. The general relation between a gene's AP repertoire and its disease susceptibility also remains largely unexplored.    Methodology/Principal Findings  Based on the differential expression ratio inferred from all human microarray data in NCBI GEO and the list of disease genes curated in public repositories, we systemically analyzed the general relation of AP repertoire with expression diversity and disease susceptibility. We found that genes with APs are more likely to be differentially expressed and/or disease associated than those with Single Promoter (SP), and genes with more APs are more likely differentially expressed and disease susceptible than those with less APs. Further analysis showed that genes with increased number of APs tend to have increased length in all aspects of gene structure including 3′ UTR, be associated with increased duplicability, and have increased connectivity in protein-protein interaction network.    Conclusions  Our genome-wide analysis provided evidences that increasing alternative promoter repertories is positively associated with differential expression and disease susceptibility.

Increasing Alternative Promoter Repertories Is Positively Associated with Differential Expression and Disease Susceptibility