The diploid genome sequence of an individual human.
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.
Levy
Samuel
S
J. Craig Venter Institute, Rockville, Maryland, USA. slevy@jcvi.org
Sutton
Granger
G
Ng
Pauline C
PC
Feuk
Lars
L
Halpern
Aaron L
AL
Walenz
Brian P
BP
Axelrod
Nelson
N
Huang
Jiaqi
J
Kirkness
Ewen F
EF
Denisov
Gennady
G
Lin
Yuan
Y
MacDonald
Jeffrey R
JR
Pang
Andy Wing Chun
AW
Shago
Mary
M
Stockwell
Timothy B
TB
Tsiamouri
Alexia
A
Bafna
Vineet
V
Bansal
Vikas
V
Kravitz
Saul A
SA
Busam
Dana A
DA
Beeson
Karen Y
KY
McIntosh
Tina C
TC
Remington
Karin A
KA
Abril
Josep F
JF
Gill
John
J
Borman
Jon
J
Rogers
Yu-Hui
YH
Frazier
Marvin E
ME
Scherer
Stephen W
SW
Strausberg
Robert L
RL
Venter
J Craig
JC
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