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Cardiovascular diseases are the primary cause of death worldwide; the identification of genes specifically expressed in the heart is thus of major biomedical interest. We carried out a comprehensive analysis of gene-expression profiles using expressed sequence tags (ESTs) to identify genes overexpressed in the human adult heart. The initial set of genes expressed in the heart was constructed by clustering and assembling ESTs from heart cDNA libraries. Expression profiles were then generated for each gene by counting their cognate ESTs in all libraries. Differential expression was assessed by applying a previously published statistical procedure to these profiles.We identified 35 cardiac-specific genes overexpressed in the heart, some of which displayed significant coexpression. Some genes had no previously recognized cardiac function. Of the 35 genes, 32 were mapped back onto the human genome sequence. According to Online Mendelian Inheritance in Man (OMIM), five genes were previously known as heart-disease genes and one gene was located in the locus of a bleeding disorder. Analysis of the promoter regions of this collection of genes provides the first list of putative regulatory elements associated with differential cardiac expression.This study shows that ESTs are still a powerful tool to identify differentially expressed genes. We present a list of genes specifically expressed in the human heart, one of which is a candidate for a bleeding disorder. In addition, we provide the first set of putative regulatory elements, the combination of which appears correlated with heart-specific gene expression.

Heart-specific genes revealed by expressed sequence tag (EST) sampling.