Towards a comprehensive structural variation map of an individual human genome

We have combined computational re-analysis of existing whole genome sequence data with novel microarray-based analysis, and detect 12,178 structural variants covering 40.6 Mb that were not reported in the initial sequencing of the first published personal genome. We estimate a total non-SNP variation content of 48.8 Mb in a single genome. Our results indicate that this genome differs from the consensus reference sequence by approximately 1.2% when considering indels/CNVs, 0.1% by SNPs and approximately 0.3% by inversions. The structural variants impact 4,867 genes, and >24% of structural variants would not be imputed by SNP-association.Our results indicate that a large number of structural variants have been unreported in the individual genomes published to date. This significant extent and complexity of structural variants, as well as the growing recognition of their medical relevance, necessitate they be actively studied in health-related analyses of personal genomes. The new catalogue of structural variants generated for this genome provides a crucial resource for future comparison studies.Comprehensive catalogues of genetic variation are crucial for genotype and phenotype correlation studies [1-8], in particular when rare or multiple genetic variants underlie traits or disease susceptibility [9,10]. Since 2007, several personal genomes have been sequenced, capturing different extents of their genetic variation content (Additional file 1) [1-8,11]. In the first publication (J Craig Venter's DNA named HuRef) [1], variants were identified based on a comparison of the Venter assembly to the National Center for Biotechnology Information (NCBI) reference genome (build 36). In total, 3,213,401 SNPs and 796,167 structural variants (SVs; here SV encompasses all non-SNP variation) were identified in that study. Similar numbers of SNPs, but significantly less SVs (ranging from approximately 137,000 to approximately 400,000) are reported in other individual genome sequencin