Abstract
The completion of the Human Genome Project revolutionized our understanding of genetics and has led to an explosion of the field; however, this database is a collection of basepairs without any key to deciphering their meaning. In terms of a wellused analogy, the human genome sequence is a library in an ancient language with no Rosetta stone. Yet there is hope. Both new technologies as well as the completion of largescale genome and transcriptome mapping projects such as ENCODE are forging the way toward developing the cipher to those basepair changes. By adding additional datasets, a greater understanding of what the human genome does and why it is the root of what makes us human is slowly being achieved. This chapter focuses on the links between DNA alterations and their downstream effects, highlighting both the layers and the players in this complex system.