Mapping translocation breakpoints by next-generation sequencing Export

@article{citeulike:2518979, abstract = {10.1101/gr.076166.108 Balanced chromosome rearrangements (BCRs) can cause genetic diseases by disrupting or inactivating specific genes, and the characterization of breakpoints in disease-associated BCRs has been instrumental in the molecular elucidation of a wide variety of genetic disorders. However, mapping chromosome breakpoints using traditional methods, such as in situ hybridization with fluorescent dye-labeled bacterial artificial chromosome clones (BAC-FISH), is rather laborious and time-consuming. In addition, the resolution of BAC-FISH is often insufficient to unequivocally identify the disrupted gene. To overcome these limitations, we have performed shotgun sequencing of flow-sorted derivative chromosomes using \^{a}€œnext-generation\^{a}€ (Illumina/Solexa) multiplex sequencing-by-synthesis technology. As shown here for three different disease-associated BCRs, the coverage attained by this platform is sufficient to bridge the breakpoints by PCR amplification, and this procedure allows the determination of their exact nucleotide positions within a few weeks. Its implementation will greatly facilitate large-scale breakpoint mapping and gene finding in patients with disease-associated balanced translocations.}, address = {Max-Planck-Institute for Molecular Genetics;}, author = {Chen, Wei and Kalscheuer, Vera and Tzschach, Andreas and Menzel, Corinna and Ullmann, Reinhard and Schulz, Marcel H. and Erdogan, Fikret and Li, Na and Kijas, Zofia and Arkesteijn, Ger and Pajares, Isidora L. and Goetz-Sothmann, Margret and Heinrich, Uwe and Rost, Imma and Dufke, Andreas and Grasshoff, Ute and Glaeser, Birgitta and Vingron, Martin and Ropers, Hilger H.}, citeulike-article-id = {2518979}, citeulike-linkout-0 = {http://dx.doi.org/10.1101/gr.076166.108}, citeulike-linkout-1 = {http://genome.cshlp.org/content/18/7/1143.abstract}, citeulike-linkout-2 = {http://genome.cshlp.org/content/18/7/1143.full.pdf}, citeulike-linkout-3 = {http://www.genome.org/cgi/content/abstract/18/7/1143}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/18326688}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=18326688}, day = {7}, doi = {10.1101/gr.076166.108}, issn = {1088-9051}, journal = {Genome Research}, keywords = {bioinformatics, mutations, nextgen, translocation, whole-genome-seq}, month = {July}, number = {7}, pages = {1143--1149}, posted-at = {2009-11-03 16:23:58}, priority = {2}, title = {Mapping translocation breakpoints by next-generation sequencing}, url = {http://dx.doi.org/10.1101/gr.076166.108}, volume = {18}, year = {2008} }

TY - JOUR ID - citeulike:2518979 L3 - citeulike-article-id:2518979 N2 - 10.1101/gr.076166.108 Balanced chromosome rearrangements (BCRs) can cause genetic diseases by disrupting or inactivating specific genes, and the characterization of breakpoints in disease-associated BCRs has been instrumental in the molecular elucidation of a wide variety of genetic disorders. However, mapping chromosome breakpoints using traditional methods, such as in situ hybridization with fluorescent dye-labeled bacterial artificial chromosome clones (BAC-FISH), is rather laborious and time-consuming. In addition, the resolution of BAC-FISH is often insufficient to unequivocally identify the disrupted gene. To overcome these limitations, we have performed shotgun sequencing of flow-sorted derivative chromosomes using “next-generation” (Illumina/Solexa) multiplex sequencing-by-synthesis technology. As shown here for three different disease-associated BCRs, the coverage attained by this platform is sufficient to bridge the breakpoints by PCR amplification, and this procedure allows the determination of their exact nucleotide positions within a few weeks. Its implementation will greatly facilitate large-scale breakpoint mapping and gene finding in patients with disease-associated balanced translocations. IS - 7 JF - Genome Research SN - 1088-9051 AD - Max-Planck-Institute for Molecular Genetics; EP - 1149 TI - Mapping translocation breakpoints by next-generation sequencing VL - 18 SP - 1143 KW - bioinformatics KW - mutations KW - nextgen KW - translocation KW - whole-genome-seq AU - Chen, Wei AU - Kalscheuer, Vera AU - Tzschach, Andreas AU - Menzel, Corinna AU - Ullmann, Reinhard AU - Schulz, Marcel AU - Erdogan, Fikret AU - Li, Na AU - Kijas, Zofia AU - Arkesteijn, Ger AU - Pajares, Isidora AU - Goetz-Sothmann, Margret AU - Heinrich, Uwe AU - Rost, Imma AU - Dufke, Andreas AU - Grasshoff, Ute AU - Glaeser, Birgitta AU - Vingron, Martin AU - Ropers, Hilger PY - 2008/07/07/ UR - http://dx.doi.org/10.1101/gr.076166.108 ER -