Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders

J Med Genet. 2004 Feb;41(2):113-9. doi: 10.1136/jmg.2003.012831.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Centromere / genetics
  • Chromosome Breakage / genetics
  • Chromosome Deletion
  • Chromosome Mapping / methods
  • Chromosome Mapping / statistics & numerical data
  • Chromosomes, Artificial, Bacterial / genetics*
  • Chromosomes, Artificial, P1 Bacteriophage / genetics*
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA / genetics
  • Electrophoresis, Gel, Pulsed-Field / standards
  • Female
  • Gene Duplication
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence / standards
  • Male
  • Mutation / genetics*
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis / methods
  • Oligonucleotide Array Sequence Analysis / statistics & numerical data


  • DNA