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Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders
  1. C J Shaw,
  2. C A Shaw,
  3. W Yu,
  4. P Stankiewicz,
  5. L D White,
  6. A L Beaudet,
  7. J R Lupski
  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  1. Correspondence to:
 Dr James R Lupski
 One Baylor Plaza, Room 604B, Houston, Texas 77030; 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, 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.

  • array-CGH
  • genomic disorders
  • low copy repeats
  • array-CGH, microarray based comparative genomic hybridisation
  • CGH, comparative genomic hybridisation
  • FISH, fluorescence in situ hybridisation
  • HMM, hidden Markov model
  • HNPP, hereditary neuropathy with liability to pressure palsies
  • LCR, low copy repeat
  • MAD, median absolute deviation
  • mCGH, metaphase-CGH
  • PFGE, pulsed field gel electrophoresis
  • SMS, Smith–Magenis syndrome

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