title: Context-based FISH localization of genomic rearrangements within chromosome 15q11.2q13 duplicons.
abstract: BACKGROUND
  Segmental duplicons (SDs) predispose to an increased frequency of chromosomal rearrangements. These rearrangements can cause a diverse range of phenotypes due to haploinsufficiency, in cis positional effects or gene interruption. Genomic microarray analysis has revealed gene dosage changes adjacent to duplicons, but the high degree of similarity between duplicon sequences has confounded unequivocal assignment of chromosome breakpoints within these intervals. In this study, we localize rearrangements within duplicon-enriched regions of Angelman/Prader-Willi (AS/PWS) syndrome chromosomal deletions with fluorescence in situ hybridization (FISH).
  
  
  RESULTS
  Breakage intervals in AS deletions were localized recursively with short, coordinate-defined, single copy (SC) and low copy (LC) genomic FISH probes. These probes were initially coincident with duplicons and regions of previously reported breakage in AS/PWS. Subsequently, probes developed from adjacent genomic intervals more precisely delineated deletion breakage intervals involving genes, pseudogenes and duplicons in 15q11.2q13. The observed variability in the deletion boundaries within previously described Class I and Class II deletion AS samples is related to the local genomic architecture in this chromosomal region.
  
  
  CONCLUSIONS
  Chromosome 15 abnormalities associated with SDs were precisely delineated at a resolution equivalent to genomic Southern analysis. This context-dependent approach can define the boundaries of chromosome rearrangements for other genomic disorders associated with SDs.
authors.affiliation: Department of Biochemistry, University of Western Ontario, Laboratories of Genome Bioinformatics and Genomic Disorders, 1151 Richmond Street, London, ON, Canada. progan@uwo.ca.
authors.forename: Wahab A
authors.initials: WA
authors.lastname: Khan
authors.forename: Joan Hm
authors.initials: JH
authors.lastname: Knoll
authors.forename: Peter K
authors.initials: PK
authors.lastname: Rogan