一種新的基因圖譜技術識別出人類基因組中有許多DNA翻轉、重組,、拷貝或刪除的地方,，意味著人的遺傳多樣性比過去認為的要高?？茖W家用這種被稱為Paired  End  Mapping的方法在兩個不同民族背景女性的基因組中發(fā)現(xiàn)了1300多處與過去測序的歐洲基因組比不同的“結構變異”,。Jan  Korbel和同時說，實際上,，結構變異也許比單個字母突變能更好地解釋個體之間的遺傳差異,。研究人員找到的這些變異的大約16%可能影響遺傳功能，圖譜可能為這些變異是如何產(chǎn)生的提供線索。

原始出處:

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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: [email protected]
Michael Snyder , E-mail: [email protected]

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.