title: Refinement of a chimpanzee pericentric inversion breakpoint to a segmental duplication cluster.
abstract: BACKGROUND
  Pericentric inversions are the most common euchromatic chromosomal differences among humans and the great apes. The human and chimpanzee karyotype differs by nine such events, in addition to several constitutive heterochromatic increases and one chromosomal fusion event. Reproductive isolation and subsequent speciation are thought to be the potential result of pericentric inversions, as reproductive boundaries form as a result of hybrid sterility.
  
  
  RESULTS
  Here we employed a comparative fluorescence in situ hybridization approach, using probes selected from a combination of physical mapping, genomic sequence, and segmental duplication analyses to narrow the breakpoint interval of a pericentric inversion in chimpanzee involving the orthologous human 15q11-q13 region. We have refined the inversion breakpoint of this chimpanzee-specific rearrangement to a 600 kilobase (kb) interval of the human genome consisting of entirely duplicated material. Detailed analysis of the underlying sequence indicated that this region comprises multiple segmental duplications, including a previously characterized duplication of the alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) in 15q13.3 and several Golgin-linked-to-PML, or LCR15, duplications.
  
  
  CONCLUSIONS
  We conclude that, on the basis of experimental data excluding the CHRNA7 duplicon as the site of inversion, and sequence analysis of regional duplications, the most likely rearrangement site is within a GLP/LCR15 duplicon. This study further exemplifies the genomic plasticity due to the presence of segmental duplications and highlights their importance for a complete understanding of genome evolution.
authors.affiliation: Department of Genetics, Center for Computational Genomics, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, OH 44106, USA. eee@cwru.edu
authors.forename: Devin P
authors.initials: DP
authors.lastname: Locke
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Archidiacono
authors.forename: Doriana
authors.initials: D
authors.lastname: Misceo
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Cardone
authors.forename: Stephane
authors.initials: S
authors.lastname: Deschamps
authors.forename: Bruce
authors.initials: B
authors.lastname: Roe
authors.forename: Mariano
authors.initials: M
authors.lastname: Rocchi
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
mesh_terms: D000818:Animals; D019457:Chromosome Breakage / Q000235:genetics*; D007446:Chromosome Inversion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D020440:Gene Duplication; D006071:Gorilla gorilla; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D005810:Multigene Family / Q000235:genetics*; D019974:Pan paniscus; D002679:Pan troglodytes / Q000235:genetics*; D011148:Pongo pygmaeus; D012689:Sequence Homology, Nucleic Acid