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

@article{korbel:structvar, abstract = {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. 10.1126/science.1149504}, address = {Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.; European Molecular Biology Laboratory, 69117 Heidelberg, Germany.}, author = {Korbel, Jan O. and Urban, Alexander E. and Affourtit, Jason P. and Godwin, Brian and Grubert, Fabian and Simons, Jan F. and Kim, Philip M. and Palejev, Dean and Carriero, Nicholas J. and Du, Lei and Taillon, Bruce E. and Chen, Zhoutao and Tanzer, Andrea and Eugenia and Chi, Jianxiang and Yang, Fengtang and Carter, Nigel P. P. and Hurles, Matthew E. E. and Weissman, Sherman M. and Harkins, Timothy T. and Gerstein, Mark B. and Egholm, Michael and Snyder, Michael}, booktitle = {Science}, citeulike-article-id = {1715073}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1149504}, citeulike-linkout-1 = {http://www.sciencemag.org/content/1149504/.abstract}, citeulike-linkout-2 = {http://www.sciencemag.org/content/1149504/.full.pdf}, citeulike-linkout-3 = {http://www.sciencemag.org/cgi/content/abstract/1149504//}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/17901297}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=17901297}, day = {19}, doi = {10.1126/science.1149504}, issn = {1095-9203}, journal = {Science}, keywords = {analysis, matepair, pair, read, thesis}, month = {October}, number = {5849}, pages = {420--426}, posted-at = {2008-05-30 14:50:54}, priority = {0}, title = {Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome}, url = {http://dx.doi.org/10.1126/science.1149504}, volume = {318}, year = {2007} }

TY - JOUR ID - korbel:structvar L3 - citeulike-article-id:1715073 N2 - 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. 10.1126/science.1149504 IS - 5849 JF - Science SN - 1095-9203 AD - Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.; European Molecular Biology Laboratory, 69117 Heidelberg, Germany. EP - 426 TI - Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome VL - 318 T2 - Science SP - 420 KW - analysis KW - matepair KW - pair KW - read KW - thesis AU - Korbel, Jan AU - Urban, Alexander AU - Affourtit, Jason AU - Godwin, Brian AU - Grubert, Fabian AU - Simons, Jan AU - Kim, Philip AU - Palejev, Dean AU - Carriero, Nicholas AU - Du, Lei AU - Taillon, Bruce AU - Chen, Zhoutao AU - Tanzer, Andrea AU - Eugenia AU - Chi, Jianxiang AU - Yang, Fengtang AU - Carter, Nigel AU - Hurles, Matthew AU - Weissman, Sherman AU - Harkins, Timothy AU - Gerstein, Mark AU - Egholm, Michael AU - Snyder, Michael PY - 2007/10/19/ UR - http://dx.doi.org/10.1126/science.1149504 ER -