title: Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders.
abstract: 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Shaw
authors.forename: C A
authors.initials: CA
authors.lastname: Shaw
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: P
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: L D
authors.initials: LD
authors.lastname: White
authors.forename: A L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: 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
chemical_list: D004247:DNA