The coding capacity of the human genome is smaller than originally expected; it is predicted that we have 25 000–40 000 genes, only twofold more than a simple organism such as the roundworm C. elegans (Pennisi, 2003). This modest increase in gene numbers is counterbalanced by enormous gains in the potential for complex interactions through alternative splicing, and in the regulatory intricacy of elements within and between genes in chromatin (Bentley, 2004) (Chapter 1). Added to this complexity is an increasing repertoire of epigenetic mechanisms which form the basis of gene silencing and genomic imprinting, including DNA methylation, histone modification and RNA interference (RNAi). These mechanisms have profound influences on developmental gene expression and, when perturbed, cancer progression and human disease (Bjornsson et al., 2004; Meehan, 2003).

Location, location, location!

The position of a gene within a eukaryotic chromosome can be a major determinant of its transcriptional properties. In the last century it was shown that the relocation of the white gene from a euchromatic position to a heterochromatic region resulted in its variegated expression in the eye of the fruit fly (Drosophila melanogaster) (Dillon and Festenstein, 2002). This observation was an example of epigenetics, which has two closely related meanings: (1) the study of the processes involved in the unfolding development of an organism, including phenomena such as X chromosome inactivation in mammalian females, and the patterning of gene silencing; (2) any mitotically and/or meiotically heritable change in gene function that cannot be explained by changes in DNA sequence (Meehan, 2003; Waddington, 1957).