Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome

作者：Jan O. Korbel, Alexander Eckehart Urban, Jason P. Affourtit, Bailey Godwin, Fabian Grubert, Jan Fredrik Simons, Philip M. Kim, Dean Palejev, Nicholas John Carriero, Lei Du, Bruce E. Taillon, Zhoutao Chen, Andrea Tanzer, Abbey Saunders, Jianxiang Chi, Fengtang Yang, Nigel P. Carter, Matthew E. Hurles, Sherman M. Weissman, Timothy T. Harkins, Mark Gerstein, Michael Egholm, Michael Snyder · 发表于：Science · 年份：2007 · DOI：10.1126/science.1149504 · 被引用次数：1196 · 研究领域：Genomics and Phylogenetic Studies、Genomic variations and chromosomal abnormalities、Chromosomal and Genetic Variations

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) approximately 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.