Epi meets genomics: Technologies for finding and reading the 5^th base

This chapter presents several high-throughput scanning techniques for the exploration and exploitation of the epigenome. It is now known that the methylation state of multiple 5th bases is susceptible to changes in disease conditions, such as cancer. The described techniques, including restriction landmark genomic scanning (RLGS), methylation-sensitive arbitrarily-primed polymerase chain reaction (MS APPCR), and differential methylation hybridization (DMH), generate unique methylation profiles of multiple DNA molecules. Another technique, MethyLight, analyzes methylation patterns of linked CpGs within individual DNA molecules in the genome. The techniques complement one another in the discovery and utilization of this rich resource of epigenome information. RLGS and MS AP-PCR analyses can result in the identification of multiple differentially methylated molecules in disease cells. This large number of candidate sites can further be evaluated by DMH. MethyLight, which is amenable to automated setup and analysis, utilizes the validated ⁵th-base markers for routine clinical diagnosis.