Early surveys of genetic variation found that two human chromosomes in the population differ at a rate of 0.1% on average (Consortium, 2005). Individual base changes, called single nucleotide polymorphisms (SNPs), are by far the most numerous variants in the genome, but SNPs are only half of the story. In 2004, two landmark studies (Iafrate et al., 2004; Sebat et al., 2004) demonstrated that submicroscopic variations (<500 kb in size) in DNA copy number (CNVs) are widespread in normal human genomes. On average, there are >1000 CNVs in the genome, accounting for ~4 million base pairs of genomic difference (Conrad et al., 2010; Mills et al., 2011). Although SNPs outnumber CNVs in the genome by three orders of magnitude, their relative contributions to genomic variation (as measured in nucleotides) are similar. Thus, in addition to 0.1% of genetic difference at the nucleotide sequence level, we now recognize another 0.1% of genetic difference at the structural level.
