Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders.
BACKGROUND
Proximal chromosome 17p is a region rich in low copy repeats (LCRs) and prone to chromosomal rearrangements. Four genomic disorders map within the interval 17p11-p12: Charcot-Marie-Tooth disease type 1A, hereditary neuropathy with liability to pressure palsies, Smith-Magenis syndrome, and dup(17)(p11.2p11.2) syndrome. While 80-90% or more of the rearrangements resulting in each disorder are recurrent, several non-recurrent deletions or duplications of varying sizes within proximal 17p also have been characterised using fluorescence in situ hybridisation (FISH).


METHODS
A BAC/PAC array based comparative genomic hybridisation (array-CGH) method was tested for its ability to detect these genomic dosage differences and map breakpoints in 25 patients with recurrent and non-recurrent rearrangements.


RESULTS
Array-CGH detected the dosage imbalances resulting from either deletion or duplication in all the samples examined. The array-CGH approach, in combination with a dependent statistical inference method, mapped 45/46 (97.8%) of the analysed breakpoints to within one overlapping BAC/PAC clone, compared with determinations done independently by FISH. Several clones within the array that contained large LCRs did not have an adverse effect on the interpretation of the array-CGH data.


CONCLUSIONS
Array-CGH is an accurate and sensitive method for detecting genomic dosage differences and identifying rearrangement breakpoints, even in LCR-rich regions of the genome.
Shaw
C J
CJ
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Shaw
C A
CA
Yu
W
W
Stankiewicz
P
P
White
L D
LD
Beaudet
A L
AL
Lupski
J R
JR
D002503:Centromere / Q000235:genetics; D019457:Chromosome Breakage / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping / Q000379:methods / Q000706:statistics & numerical data; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics*; D027042:Chromosomes, Artificial, P1 Bacteriophage / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field / Q000592:standards; D005260:Female; D020440:Gene Duplication; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000592:standards; D008297:Male; D009154:Mutation / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data
D004247:DNA