Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome
Open accessAbstract
Structural variation of the genome involves kilobase- to megabase-sized deletions, duplications, insertions, inversions, and complex combinations of rearrangements. We introduce high-throughput and massive paired-end mapping (PEM), a large-scale genome-sequencing method to identify structural variants (SVs) ∼3 kilobases (kb) or larger that combines the rescue and capture of paired ends of 3-kb fragments, massive 454 sequencing, and a computational approach to map DNA reads onto a reference genome. PEM was used to map SVs in an African and in a putatively European individual and identified shared and divergent SVs relative to the reference genome. Overall, we fine-mapped more than 1000 SVs and documented that the number of SVs among humans is much larger than initially hypothesized; many of the SVs potentially affect gene function. The breakpoint junction sequences of more than 200 SVs were determined with a novel pooling strategy and computational analysis. Our analysis provided insights into the mechanisms of SV formation in humans.
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High levels of structural variation, including copy-number variation, had previously been described for cell defense and sensory perception.
“High levels of structural variation, including copy-number variation, were previously described for both processes15,22,39.”
From Mapping copy number variation by population-scale genome sequencing (2011) · cites this paper as [15]
Nucleotide-resolution breakpoint information enables inference of structural-variant formation mechanisms.
“Nucleotide resolution breakpoint information enables inference of SV formation mechanisms15,22.”
From Mapping copy number variation by population-scale genome sequencing (2011) · cites this paper as [15]
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- Authors
- Korbel, J. O., Urban, A. E., Affourtit, J. P., Godwin, B., Grubert, F., Simons, J. F., Kim, P. M., Palejev, D., Carriero, N. J., Du, L., Taillon, B. E., Chen, Z., Tanzer, A., Saunders, A. C. E., Chi, J., Yang, F., Carter, N. P., Hurles, M. E., Weissman, S. M., Harkins, T. T., Gerstein, M. B., Egholm, M., & Snyder, M.
- Affiliations
- Yale University (US)
- Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.
- Corresponding author
- Korbel, Jan O.
- Urban, Alexander Eckehart
- Affourtit, Jason P.
- Egholm, Michael
- Snyder, Michael
- ORCID
- Venue
- Science
- Published
- 2007-10-19
- Volume
- 318
- Issue
- 5849
- Pages
- 420-426
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2674581
- OpenAlex
- W2140869203
- Cited by
- 1,163
- References
- 23
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 20 · 2023: 18 · 2022: 22 · 2021: 26 · 2020: 53 · 2019: 42 · 2018: 43 · 2017: 42 · 2016: 44 · 2015: 75 · 2014: 77 · 2013: 83 · 2012: 100
- FWCI
- 67.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Publikation Server (Leipzig University) (submittedVersion)
- Funders
- Wellcome Trust (077014, 077008)
- National Institutes of Health (1s10rr019895-01)
- National Center for Research Resources (RR 19895, S10_RR019895)
- 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, human genome, deletion, duplication, insertion, inversion, fine mapping, 454 pyrosequencing
- MeSH terms
- Chromosome Mapping, Female, Humans, Chromosome Inversion, Mutation, Recombination, Genetic, Repetitive Sequences, Nucleic Acid, Genetic Variation, Genome, Human, Mutagenesis, Insertional, Sequence Deletion, Sequence Analysis, DNA, Retroelements, Computational Biology, Oligonucleotide Array Sequence Analysis, Gene Fusion
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