Copy number variations and chronic diseases

In the beginning of the millennium we were astounded by the publication of the haploid human genome (Lander et al. Nature 409:860–921, 2001; Venter et al. Science 291:1304–1351, 2001). Now a decade later we have moved on to routine sequencing of thousands of genomes (1000 Genomes Project Consortium et al. Nature 467:1061–1073, 2010). The publication of the reference human genome enabled a vast array of technologies, which in turn provided new discoveries. A surprising and important discovery of this era was that copy number variation (CNV) is common between individual genomes, which has generated increased interest in the role of CNVs in human disease. We have clear evidence that CNVs play a role in human disease, but the extent to which this type of genetic variation affects biological traits that are multifactorial in etiology remains undiscovered. In this chapter we lay out the fundamental discoveries that have led to our current understanding of the role of CNVs in human disease. We provide a description of copy number variation, mechanisms of formation, and potential roles in various models of the heritable component of complex disorders.