The Diploid Genome Sequence of an Individual Human

By S. Levy, Granger G. Sutton, Pauline Crystal Ng, L. Feuk, A. Halpern, Brian Walenz, Nelson Axelrod, Jiaqi Huang, E. Kirkness, Gennady Denisov and 22 more. PLoS Biology, 2007

1,867 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/337cc132771ce4a293f4ff547ef7960a5cea9d5f

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Citations in the corpus

Next generation disparities in human genomics: concerns and remedies. (2009, methodology): “The first human genome sequenced was of Craig Venter, of European origin, published in September 2007, and sequenced using Sanger sequencing [ 37 ].”
Natural genetic variation caused by small insertions and deletions in the human genome. (2011, background): “We also examined five of the personal human genomes that have been sequenced, including four ‘‘healthy’’ genomes (Levy et al. 2007; Bentley et al. 2008; Wang et al. 2008; Wheeler et al. 2008) and the genome of a patient with acute myelogenous leukemia (Ley et al. 2008).”
Origins and functional impact of copy number variation in the human genome (2009, background): “We took five complementary approaches to identify dispersed duplications among our CNVs: (1) precise mapping to inter-chromosomal segmental duplications; (2) evidence for inter-chromosomal mappings from sequence data(34); (3) inter-chromosomal linkage disequilibrium; (4) poly-A and target site dupli”
Genome graphs and the evolution of genome inference (2017, background): “Highly repetitive sequences are particularly prevalent in biologically important centromeric regions (Levyet al. 2007; Miga 2015), and one of the most fundamental biological structures, theribosome,is encodedin repetitive sequence (Levy et al. 2007; Miga 2015).”
HapCUT2: robust and accurate haplotype assembly for diverse sequencing technologies (2017, methodology): “Other methods such as DGS (Levy et al. 2007), MixSIH (Matsumoto and Kiryu 2013), and HapTree (Berger et al. 2014) did not perform as well on the data sets evaluated in this study.”
PacBio Sequencing and Its Applications (2015, background): “In the Sanger-sequenced diploid genome of an individual human, 74% of a total of 12.3 Mb of variant bases were SVs [49].”
A Draft Sequence of the Neandertal Genome (2010, neutral): “To determine whether these segments are unusual in their divergence to other present-day humans, we examined the divergence of each segment to the genome of Craig Venter (77).”
Toward better understanding of artifacts in variant calling from high-coverage samples (2014, methodology): “Since the sequencing of the ﬁrst personal genome (Levy et al., 2007) and in particular the ﬁrst genomes sequenced with the Illumina technologies (Bentley et al., 2008; Wang et al., 2008), resequencing has been widely used for personal and cancer genomics (Watson et al., 2013), for the discovery of…”