Mapping translocation breakpoints by next-generation sequencing
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA108267
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Reinhard Ullmann
PROVIDER: E-GEOD-10115 | ArrayExpress | 2010-05-22
REPOSITORIES: ArrayExpress
Publications
Mapping translocation breakpoints by next-generation sequencing.
Chen Wei W Kalscheuer Vera V Tzschach Andreas A Menzel Corinna C Ullmann Reinhard R Schulz Marcel Holger MH Erdogan Fikret F Li Na N Kijas Zofia Z Arkesteijn Ger G Pajares Isidora Lopez IL Goetz-Sothmann Margret M Heinrich Uwe U Rost Imma I Dufke Andreas A Grasshoff Ute U Glaeser Birgitta B Vingron Martin M Ropers H Hilger HH
Genome research 20080307 7
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 additio ...[more]
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Project description: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.
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