Towards a comprehensive structural variation map of an individual human genome
Open accessAbstract
Background: Several genomes have now been sequenced, with millions of genetic variants annotated. While significant progress has been made in mapping single nucleotide polymorphisms (SNPs) and small (<10 bp) insertion/deletions (indels), the annotation of larger structural variants has been less comprehensive. It is still unclear to what extent a typical genome differs from the reference assembly, and the analysis of the genomes sequenced to date have shown varying results for copy number variation (CNV) and inversions. Results: We have combined computational re-analysis of existing whole genome sequence data with novel microarray-based analysis, and detect 12,178 structural variants covering 40.6 Mb that were not reported in the initial sequencing of the first published personal genome. We estimate a total non-SNP variation content of 48.8 Mb in a single genome. Our results indicate that this genome differs from the consensus reference sequence by approximately 1.2% when considering indels/CNVs, 0.1% by SNPs and approximately 0.3% by inversions. The structural variants impact 4,867 genes, and >24% of structural variants would not be imputed by SNP-association. Conclusions: Our results indicate that a large number of structural variants have been unreported in the individual genomes published to date. This significant extent and complexity of structural variants, as well as the growing recognition of their medical relevance, necessitate they be actively studied in health-related analyses of personal genomes. The new catalogue of structural variants generated for this genome provides a crucial resource for future comparison studies.
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Compared with a recent individual-genome survey, the set had a similar deletion size distribution but different size distributions for other structural-variant classes, reflecting ascertainment differences.
“we also compared our set to a recent survey of SVs in an individual genome37 based on capillary sequencing and array-based analyses24, and observed a similar size distribution for deletions, but differences in the size distributions of other SV classes, reflecting underlying differences in SV ascertainment”
From Mapping copy number variation by population-scale genome sequencing (2011) · cites this paper as [24]
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- Authors
- Pang, A. W., MacDonald, J. R., Pinto, D., Wei, J., Rafiq, M. A., Conrad, D. F., Park, H., Hurles, M. E., Lee, C., Venter, J. C., Kirkness, E. F., Levy, S., Feuk, L., & Scherer, S. W.
- Affiliations
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Wellcome Sanger Institute (GB)
- Brigham and Women's Hospital (US)
- J. Craig Venter Institute (US)
- Uppsala University (SE)
- Corresponding author
- Feuk, Lars
- Scherer, Stephen W
- ORCID
- Venue
- Genome Biology
- Published
- 2010-05-19
- Volume
- 11
- Issue
- 5
- Pages
- R52-R52
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC2898065
- OpenAlex
- W2153994884
- Cited by
- 335
- References
- 47
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 20 · 2023: 20 · 2022: 11 · 2021: 17 · 2020: 19 · 2019: 24 · 2018: 14 · 2017: 17 · 2016: 14 · 2015: 25 · 2014: 21 · 2013: 36 · 2012: 34
- FWCI
- 19.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- TSpace (University of Toronto) (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- GlaxoSmithKline
- Canadian Institute for Advanced Research
- Genome Canada
- Ontario Genomics
- Göran Gustafssons Stiftelser
- Ontario Genomics Institute
- Koninklijke Nederlandse Akademie van Wetenschappen
- Stiftelsen för Strategisk Forskning
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (825.06.031)
- University of Toronto
- Hospital for Sick Children
- Sickkids Research Institute
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- structural variants, copy number variation, chromosomal inversions, insertion-deletion variants, personal genome, variant imputation
- MeSH terms
- Chromosome Mapping, Gene Frequency, Humans, Mutation, Reproducibility of Results, Gene Library, Genome, Human, Polymerase Chain Reaction, In Situ Hybridization, Fluorescence, Sequence Analysis, DNA, Base Pairing, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Databases, Genetic, Comparative Genomic Hybridization, DNA Copy Number Variations
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