Although Jim Watson's genome hasn't been through peer review yet, and Craig Venter’s genome doesn’t have a slick web browser like Jim’s genome yet, we’ve seen enough to ask – what next? Someone at the meeting today got some laughs accidentally when they said that they were comparing Craig’s genome to the human genome. Clearly this is a time requiring great caution. So our first question is: where are we with these first two complete diploid genomes? Well, they’re neither complete nor the first. The Craigome has over 4500 gaps (a bit more than the 341 gaps in the haploid 2004 HGP genome). The first human diploid sequence nod goes to the 269 HapMap genomes published in Oct 2005. Nevertheless we now have the first two non-anonymous personal genomes (hopefully millions someday). Oh, and what is it with press-release that our genomes have higher variation than previously thought? The 0.5% variation observed includes a near-perfect fit to the long-known 0.06% SNP frequency, a 0.08% frequency of smaller indels about twice that seen in 330 genes from Seattle studies, and the remainder being copy-number variants (CNV) 87% of which have been described previously. Just like the number of genes in the genome in 2001, the beauty and the news is in the details not in the summary stats.

The era of personal genomics is upon us, with advances in technologies such as DNA sequencing and genotyping fuelling the fires. Personal genomics is a story of researchers looking for genetic clues to our most common diseases, of dazzling advances in genetic analysis technology and of lingering questions about how the public will view and use the information.

Presented here is a genome sequence of an individual human. It was produced from ∼32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information.