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Mapping translocation breakpoints by next-generation sequencing

Item Type:Article
Title:Mapping translocation breakpoints by next-generation sequencing
Creators Name:Chen, W., Kalscheuer, V., Tzschach, A., Menzel, C., Ullmann, R., Schulz, M.H., Erdogan, F., Li, N., Kijas, Z., Arkesteijn, G., Pajares, I.L., Goetz-Sothmann, M., Heinrich, U., Rost, I., Dufke, A., Grasshoff, U., Glaeser, B., Vingron, M. and Ropers, H.H.
Abstract: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.
Keywords:Base Sequence, Chromosome Breakage, Chromosome Mapping, Mental Retardation, Molecular Sequence Data, DNA Sequence Analysis, Genetic Translocation
Source:Genome Research
Publisher:Cold Spring Harbor Laboratory Press
Page Range:1143-1149
Date:July 2008
Official Publication:https://doi.org/10.1101/gr.076166.108
PubMed:View item in PubMed

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