Human Genome Structural Variation January 23 , 2006

Rationale. The last three years have brought considerable progress in understanding the nature and patterns of single nucleotide polymorphism within the human species. Of the estimated 10-15 million common SNPs, a large fraction have already been discovered and 3.8 million SNPs converted to genotyping assays, providing the community with a framework to investigate associations between common SNPs and human disease (Consortium 2005; Hinds et al. 2005b). By contrast, our understanding of structural variation within the human genome lags far behind. Several recent publications (Fredman et al. 2004; Iafrate et al. 2004; Sebat et al. 2004; Conrad et al. 2005; Gonzalez et al. 2005; Hinds et al. 2005a; McCarroll et al. 2005; Sharp et al. 2005; Stefansson et al. 2005; Tuzun et al. 2005) have described large scale (>50 kb) and intermediate-size structural variation (>500 bp) in the human genome, revealing that: