High-resolution breakpoint analysis provides evidence for the sequence-directed nature of genome rearrangements in hereditary disorders Journal Article


Authors: Kovac, M. B.; Kovacova, M.; Bachraty, H.; Bachrata, K.; Piscuoglio, S.; Hutter, P.; Ilencikova, D.; Bartosova, Z.; Tomlinson, I.; Roethlisberger, B.; Heinimann, K.
Article 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. This study aimed 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 genomic rearrangements (GRs) in hereditary colorectal cancer patients, and subsequently created an algorithm, termed recombination type ratio (RTR), which correctly predicts the propensity of rearrangements with respect to homologous (hGR) versus nonhomologous recombination (nhGR) events.
Keywords: gene sequence; major clinical study; gene deletion; cancer patient; homologous recombination; germ line; gene rearrangement; gene duplication; genome; genetic disorder; chromosome 2; chromosome 3; chromosome 7; genetic algorithm; hereditary colorectal cancer; chromosome 5; human; priority journal; article; dna signatures; genome architecture; germ-line genome rearrangements; hereditary disorders; nonhomologous recombination; recombination type ratio; sequence-directed mutation
Journal Title: Human Mutation
Volume: 36
Issue: 2
ISSN: 1059-7794
Publisher: Wiley Liss  
Date Published: 2015-02-01
Start Page: 250
End Page: 259
Language: English
DOI: 10.1002/humu.22734
PROVIDER: scopus
PUBMED: 25418510
DOI/URL:
Notes: Export Date: 2 March 2015 -- Source: Scopus
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