important research on proximal chromosone 17p - not only CMT 1A

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Abstract from Journal of Medical Genetics 2004 Feb;41(2):113-9.

Comparative genomic hybridisation using a proximal 17p BAC/PAC array

detects rearrangements responsible for four genomic disorders.

Shaw CJ, Shaw CA, Yu W, Stankiewicz P, White LD, Beaudet AL, Lupski JR.

Department of Molecular and Human Genetics, Baylor College of Medicine,

Houston, Texas, USA.

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, -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.