title: Molecular distinction between true centric fission and pericentric duplication-fission.
abstract: Centromere (centric) fission, also known as transverse or lateral centric misdivision, has been defined as the splitting of one functional centromere of a metacentric or submetacentric chromosome to produce two derivative centric chromosomes. It has been observed in a range of organisms and has been ascribed an important role in karyotype evolution; however, the underlying mechanisms remain unknown. We have investigated four cases of apparent centric fission in humans. Two cases show a missing chromosome 22 or 18 that is replaced by two centric ring products, a third case shows two chromosome-10-derived telocentric chromosomes, whereas a fourth case involves the formation of two chromosome-18-derived isochromosomes. In all four cases, results of gross cytogenetic and fluorescence in situ hybridisation analyses were consistent with a simple centric fission event. However, detailed molecular analyses provided evidence in support of centromere duplication as a predisposing mechanism for the observed chromosomal breakage in two of the cases. Results for the third case are consistent with direct centric fission not involving centromere pre-duplication as the likely mechanism. Insufficient material has precluded the further study of the fourth case. The data provide the first molecular evidence for centromere pre-duplication as a possible mechanism to explain the classically assumed simple "centric fission" events in clinical cytogenetics, karyotype evolution and speciation.
authors.affiliation: Chromosome Research Laboratory, Murdoch Childrens Research Institute and Department of Paediatrics, Royal Children's Hospital, Parkville, VIC, 3052, Australia.
authors.forename: Jo
authors.initials: J
authors.lastname: Perry
authors.forename: Sara
authors.initials: S
authors.lastname: Nouri
authors.forename: Phung
authors.initials: P
authors.lastname: La
authors.forename: Art
authors.initials: A
authors.lastname: Daniel
authors.forename: Zhanhe
authors.initials: Z
authors.lastname: Wu
authors.forename: Stuart
authors.initials: S
authors.lastname: Purvis-Smith
authors.forename: Emma
authors.initials: E
authors.lastname: Northrop
authors.forename: K H Andy
authors.initials: KH
authors.lastname: Choo
authors.forename: Howard R
authors.initials: HR
authors.lastname: Slater
mesh_terms: D005455:Fluorescent Antibody Technique; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D018895:Microsatellite Repeats / Q000235:genetics