title: Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genome.
abstract: We identified complex genomic rearrangements consisting of intermixed duplications and triplications of genomic segments at the MECP2 and PLP1 loci. These complex rearrangements were characterized by a triplicated segment embedded within a duplication in 11 unrelated subjects. Notably, only two breakpoint junctions were generated during each rearrangement formation. All the complex rearrangement products share a common genomic organization, duplication-inverted triplication-duplication (DUP-TRP/INV-DUP), in which the triplicated segment is inverted and located between directly oriented duplicated genomic segments. We provide evidence that the DUP-TRP/INV-DUP structures are mediated by inverted repeats that can be separated by >300 kb, a genomic architecture that apparently leads to susceptibility to such complex rearrangements. A similar inverted repeat-mediated mechanism may underlie structural variation in many other regions of the human genome. We propose a mechanism that involves both homology-driven events, via inverted repeats, and microhomologous or nonhomologous events.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Claudia M B
authors.initials: CM
authors.lastname: Carvalho
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Ramocki
authors.forename: Davut
authors.initials: D
authors.lastname: Pehlivan
authors.forename: Luis M
authors.initials: LM
authors.lastname: Franco
authors.forename: Claudia
authors.initials: C
authors.lastname: Gonzaga-Jauregui
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
authors.forename: Alanna
authors.initials: A
authors.lastname: McCall
authors.forename: Eniko Karman
authors.initials: EK
authors.lastname: Pivnick
authors.forename: Stacy
authors.initials: S
authors.lastname: Hines-Dowell
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Seaver
authors.forename: Linda
authors.initials: L
authors.lastname: Friehling
authors.forename: Sansan
authors.initials: S
authors.lastname: Lee
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Smith
authors.forename: Daniela
authors.initials: D
authors.lastname: Del Gaudio
authors.forename: Marjorie
authors.initials: M
authors.lastname: Withers
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: John W
authors.initials: JW
authors.lastname: Belmont
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: P J
authors.initials: PJ
authors.lastname: Hastings
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D015321:Gene Rearrangement; D015894:Genome, Human; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2