title: High-resolution breakpoint analysis provides evidence for the sequence-directed nature of genome rearrangements in hereditary disorders.
abstract: Although most of the pertinent data on the sequence-directed processes leading to genome rearrangements (GRs) have come from studies on somatic tissues, little is known about GRs in the germ line of patients with hereditary disorders. This study aims at identifying DNA motifs and higher order structures of genome architecture, which can result in losses and gains of genetic material in the germ line. We first identified candidate motifs by studying 112 pathogenic germ-line GRs in hereditary colorectal cancer patients, and subsequently created an algorithm, termed recombination type ratio, which correctly predicts the propensity of rearrangements with respect to homologous versus nonhomologous recombination events.
authors.affiliation: Research Group Human Genomics, Department of Biomedicine, University of Basel, Basel, Switzerland; Medical Genetics, University Hospital Basel, Basel, Switzerland; The Wellcome Trust Centre for Human Genetics, University of Oxford, Old Road Campus, Oxford, UK.
authors.forename: Michal B
authors.initials: MB
authors.lastname: Kovac
authors.forename: Monika
authors.initials: M
authors.lastname: Kovacova
authors.forename: Hynek
authors.initials: H
authors.lastname: Bachraty
authors.forename: Katarina
authors.initials: K
authors.lastname: Bachrata
authors.forename: Salvatore
authors.initials: S
authors.lastname: Piscuoglio
authors.forename: Pierre
authors.initials: P
authors.lastname: Hutter
authors.forename: Denisa
authors.initials: D
authors.lastname: Ilencikova
authors.forename: Zdena
authors.initials: Z
authors.lastname: Bartosova
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Benno
authors.initials: B
authors.lastname: Roethlisberger
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D011125:Adenomatous Polyposis Coli / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics; D056905:Chromosome Breakpoints; D002874:Chromosome Mapping; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D059765:Homologous Recombination; D006801:Humans; D000070976:Mismatch Repair Endonuclease PMS2; D058977:Molecular Sequence Annotation; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C555337:APC protein, human; D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: DNA signatures; genome architecture; germ-line genome rearrangements; hereditary colorectal cancer; hereditary disorders; homologous recombination; nonhomologous recombination; recombination type ratio; sequence-directed mutation