Just about everybody in the world, both scientist and non-scientist alike, knows that the a complete copy of the human genome has been sequenced. However, what the vast majority of scientists and most probably nearly all of non-scientists don't know is that the full sequence is in fact only haploid copy. That is a set of chromosomes containing only one member of each chromosome pair. Additionally, the Human Genome Project's genome consisted of a group of individuals from a variety of different racial backgrounds.

Well, there is now a new gold standard for human genome sequencing - a complete full diploid set of one person's chromosomes. And guess who that person is....



J. Craig Venter of course!


Here is a link to the full text open-access copy of the publication on PLOS!

Samuel Levy, Granger Sutton, Pauline C. Ng, Lars Feuk, Aaron L. Halpern, Brian P. Walenz, Nelson Axelrod, Jiaqi Huang, Ewen F. Kirkness, Gennady Denisov, Yuan Lin, Jeffrey R. MacDonald, Andy Wing Chun Pang, Mary Shago, Timothy B. Stockwell, Alexia Tsiamouri, Vineet Bafna, Vikas Bansal, Saul A. Kravitz, Dana A. Busam, Karen Y. Beeson, Tina C. McIntosh, Karin A. Remington, Josep F. Abril, John Gill, Jon Borman, Yu-Hui Rogers, Marvin E. Frazier, Stephen W. Scherer, Robert L. Strausberg, J. Craig Venter. The Diploid Genome Sequence of an Individual Human. PLoS Biol 5(10): e254 doi:10.1371/journal.pbio.0050254

Abstract:
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 (2206 bp), 292,102 heterozygous insertion/deletion events (indels)(1571 bp), 559,473 homozygous indels (182,711 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.

Author's Summary:
We have generated an independently assembled diploid human genomic DNA sequence from both chromosomes of a single individual (J. Craig Venter). Our approach, based on whole-genome shotgun sequencing and using enhanced genome assembly strategies and software, generated an assembled genome over half of which is represented in large diploid segments (>200 kilobases), enabling study of the diploid genome. Comparison with previous reference human genome sequences, which were composites comprising multiple humans, revealed that the majority of genomic alterations are the well-studied class of variants based on single nucleotides (SNPs). However, the results also reveal that lesser-studied genomic variants, insertions and deletions, while comprising a minority (22%) of genomic variation events, actually account for almost 74% of variant nucleotides. Inclusion of insertion and deletion genetic variation into our estimates of interchromosomal difference reveals that only 99.5% similarity exists between the two chromosomal copies of an individual and that genetic variation between two individuals is as much as five times higher than previously estimated. The existence of a well-characterized diploid human genome sequence provides a starting point for future individual genome comparisons and enables the emerging era of individualized genomic information.