title: The diploid genome sequence of an individual human.
abstract: Presented here is a genome sequence of an individual human. It was produced from approximately 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.
authors.affiliation: J. Craig Venter Institute, Rockville, Maryland, USA. slevy@jcvi.org
authors.forename: Samuel
authors.initials: S
authors.lastname: Levy
authors.forename: Granger
authors.initials: G
authors.lastname: Sutton
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ng
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Halpern
authors.forename: Brian P
authors.initials: BP
authors.lastname: Walenz
authors.forename: Nelson
authors.initials: N
authors.lastname: Axelrod
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Huang
authors.forename: Ewen F
authors.initials: EF
authors.lastname: Kirkness
authors.forename: Gennady
authors.initials: G
authors.lastname: Denisov
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: MacDonald
authors.forename: Andy Wing Chun
authors.initials: AW
authors.lastname: Pang
authors.forename: Mary
authors.initials: M
authors.lastname: Shago
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Stockwell
authors.forename: Alexia
authors.initials: A
authors.lastname: Tsiamouri
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
authors.forename: Vikas
authors.initials: V
authors.lastname: Bansal
authors.forename: Saul A
authors.initials: SA
authors.lastname: Kravitz
authors.forename: Dana A
authors.initials: DA
authors.lastname: Busam
authors.forename: Karen Y
authors.initials: KY
authors.lastname: Beeson
authors.forename: Tina C
authors.initials: TC
authors.lastname: McIntosh
authors.forename: Karin A
authors.initials: KA
authors.lastname: Remington
authors.forename: Josep F
authors.initials: JF
authors.lastname: Abril
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.forename: Jon
authors.initials: J
authors.lastname: Borman
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Rogers
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Frazier
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Robert L
authors.initials: RL
authors.lastname: Strausberg
authors.forename: J Craig
authors.initials: JC
authors.lastname: Venter
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping / Q000295:instrumentation / Q000379:methods; D002877:Chromosomes, Human; D041322:Chromosomes, Human, Y / Q000235:genetics; D004171:Diploidy; D018628:Gene Dosage; D015894:Genome, Human; D005838:Genotype; D006239:Haplotypes; D016045:Human Genome Project; D006801:Humans; D054643:INDEL Mutation; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000295:instrumentation / Q000379:methods