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Korbel, Jan O; Urban, Alexander Eckehart; Affourtit, Jason P; Godwin, Brian; Grubert, Fabian; Simons, Jan Fredrik; Kim, Philip M; Palejev, Dean; Carriero, Nicholas J; Du, Lei; Taillon, Bruce E; Chen, Zhoutao; Tanzer, Andrea; Saunders, A.C. Eugenia; Chi, Jianxiang; Yang, Fengtang; Carter, Nigel P; Hurles, Matthew E; Weissman, Sherman M; Harkins, Timothy T; Gerstein, Mark B; Egholm, Michael; Snyder, Michael
Science (American Association for the Advancement of Science), 10/2007, Letnik: 318, Številka: 5849Journal Article
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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