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Ultra-high resolution array painting facilitates breakpoint sequencing

¹ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
² NimbleGen Systems, Madison, Wisconsin, USA
³ Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire, UK

Correspondence to:
N P Carter
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK; npc{at}sanger.ac.uk] Objective: To describe a considerably advanced method of array painting, which allows the rapid, ultra-high resolution mapping of translocation breakpoints such that rearrangement junction fragments can be amplified directly and sequenced.

Method: Ultra-high resolution array painting involves the hybridisation of probes generated by the amplification of small numbers of flow-sorted derivative chromosomes to oligonucleotide arrays designed to tile breakpoint regions at extremely high resolution.

Results and discussion: How ultra-high resolution array painting of four balanced translocation cases rapidly and efficiently maps breakpoints to a point where junction fragments can be amplified easily and sequenced is demonstrated. With this new development, breakpoints can be mapped using just two array experiments: the first using whole-genome array painting to tiling resolution large insert clone arrays, the second using ultra-high-resolution oligonucleotide arrays targeted to the breakpoint regions. In this way, breakpoints can be mapped and then sequenced in a few weeks.

Abbreviations: CGH, comparative genomic hybridisation; FISH, fluorescence in situ hybridisation; LINE, long interspersed element; PCR, polymerase chain reaction; SINE, short interspersed element

Keywords: array painting; array-CGH; oligonucleotide array; transloction breakpoints

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