Author:
Chen Wei,Kalscheuer Vera,Tzschach Andreas,Menzel Corinna,Ullmann Reinhard,Schulz Marcel Holger,Erdogan Fikret,Li Na,Kijas Zofia,Arkesteijn Ger,Pajares Isidora Lopez,Goetz-Sothmann Margret,Heinrich Uwe,Rost Imma,Dufke Andreas,Grasshoff Ute,Glaeser Birgitta,Vingron Martin,Ropers H. Hilger
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.
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics (clinical),Genetics
Cited by
110 articles.
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