Ultra-high resolution array painting facilitates breakpoint sequencing

Susan M Gribble ¹, Dimitrios Kalaitzopoulos ¹, Deborah C Burford ¹, Elena Prigmore ¹, Rebbeca R Selzer ², Bee L Ng ¹, Nick S. W. Matthews ¹, Keith M Porter ¹, Rebecca Curley ¹, Sarah J Lindasy ¹, Julia Baptista ³, Todd A Richmond ² and Nigel P Carter ^1*

¹ The Wellcome Trust Sanger Institute, United Kingdom
² 2. NimbleGen Systems Inc., United States
³ WRGL, United Kingdom

^* To whom correspondence should be addressed. E-mail: npc{at}sanger.ac.uk.

Accepted 3 August 2006

Abstract

Objective: The authors describe a significant advance of the 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 PCR of small numbers of flow sorted derivative chromosomes to oligonucelotide arrays designed to tile breakpoint regions at extremely high resolution.

Results and Discussion: The authors demonstrate 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. With this new development, breakpoints can be mapped using just two array experiments, the first utilising whole genome array painting to tiling resolution large insert clone arrays, the second utilising ultra-high reolution oligonucleotide arrays targeted to the breakpoint regions. In this way breakpoints can be mapped and then sequenced in a matter of a few weeks.

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

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