Ultra-high resolution array painting facilitates breakpoint sequencing.
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.


METHODS
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.


CONCLUSIONS
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.
Gribble
S M
SM
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Kalaitzopoulos
D
D
Burford
D C
DC
Prigmore
E
E
Selzer
R R
RR
Ng
B L
BL
Matthews
N S W
NS
Porter
K M
KM
Curley
R
R
Lindsay
S J
SJ
Baptista
J
J
Richmond
T A
TA
Carter
N P
NP
D000328:Adult; D002675:Child, Preschool; D019457:Chromosome Breakage; D002874:Chromosome Mapping / Q000379:methods*; D020223:Chromosome Painting / Q000379:methods*; D002877:Chromosomes, Human / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D014178:Translocation, Genetic