Chapter 11.1 - Genomic Analyses in the Developing and Diseased Heart

Abstract

This chapter discusses different approaches to cardiovascular genomics and their implications. Gene expression profiling on a large scale first became possible with the advent of tools to manipulate DNA and RNA. Subtraction hybridization (Hedrick et al., 1984) and the generation of tissue-specific cDNA libraries were the initial strategies used to pursue a broader analysis of gene expression and promote the discovery of novel tissue-restricted genes. New techniques emerged such as “differential display” and serial analysis of gene expression (SAGE), which were valuable tools for cardiovascular gene discovery. The successful sequencing of the human genome in 2001 revealed that the three billion nucleotide bases comprised approximately 20,000–25,000 genes. The Human Genome Project also generated expressed sequence tags (ESTs), which are short double-stranded fragments usually hundreds of bases in length that were derived from tissue-specific cDNA libraries and used for gene discovery. The sequencing of the human genome, the need for efficient whole-genome screening strategies, and engineering advances all led to the development of the cDNA chip in the early-1990s. The first scientific report using a cDNA platform was published in 1992 (Liang and Pardee, 1992). Since that time, studies in many species utilizing transcriptome analysis (i.e., DNA chips) to interrogate transcript expression have increased exponentially, and now provide a voluminous amount of data to the scientific community.