一种新的基因图谱技术识别出人类基因组中有许多DNA翻转、重组、拷贝或删除的地方，意味着人的遗传多样性比过去认为的要高。科学家用这种被称为Paired End Mapping的方法在两个不同民族背景女性的基因组中发现了1300多处与过去测序的欧洲基因组比不同的“结构变异”。Jan Korbel和同时说，实际上，结构变异也许比单个字母突变能更好地解释个体之间的遗传差异。研究人员找到的这些变异的大约16%可能影响遗传功能，图谱可能为这些变异是如何产生的提供线索。
原始出处:
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Published Online September 27, 2007
Science DOI: 10.1126/science.1149504
Submitted on August 21, 2007
Accepted on September 13, 2007
Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome
Jan O. Korbel 1, Alexander Eckehart Urban 2, Jason P. Affourtit 3, Brian Godwin 3, Fabian Grubert 4, Jan Fredrik Simons 3, Philip M. Kim 5, Dean Palejev 4, Nicholas J. Carriero 6, Lei Du 3, Bruce E. Taillon 3, Zhoutao Chen 3, Andrea Tanzer 7, A. C. Eugenia Saunders 2, Jianxiang Chi 8, Fengtang Yang 8, Nigel P. Carter 8, Matthew E. Hurles 8, Sherman M. Weissman 4, Timothy T. Harkins 9, Mark B. Gerstein 10, Michael Egholm 3*, Michael Snyder 11*
1 Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.; European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
2 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
3 454 Life Sciences, A Roche Company, Branford, CT 06405, USA.
4 Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
5 Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.
6 Department of Computer Science, Yale University, New Haven, CT 06520, USA.
7 Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06520, USA.; Department of Computer Science, University of Leipzig, 04107 Leipzig, Germany.; Institute for Theoretical Chemistry, University of Vienna, 1090 Vienna, Austria.
8 The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
9 Roche Applied Science, Indianapolis, IN 46250, USA.
10 Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.; Department of Computer Science, Yale University, New Haven, CT 06520, USA.; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
11 Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
* To whom correspondence should be addressed.
Michael Egholm , E-mail: megholm@454.com
Michael Snyder , E-mail: michael.snyder@yale.edu
These authors contributed equally to this work.
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 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 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.
