title: Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations.
abstract: Large-scale analysis of balanced chromosomal translocation breakpoints has shown nonhomologous end joining and microhomology-mediated repair to be the main drivers of interchromosomal structural aberrations. Breakpoint sequences of de novo unbalanced translocations have not yet been investigated systematically. We analyzed 12 de novo unbalanced translocations and mapped the breakpoints in nine. Surprisingly, in contrast to balanced translocations, we identify nonallelic homologous recombination (NAHR) between (retro)transposable elements and especially long interspersed elements (LINEs) as the main mutational mechanism. This finding shows yet another involvement of (retro)transposons in genomic rearrangements and exposes a profoundly different mutational mechanism compared with balanced chromosomal translocations. Furthermore, we show the existence of compound maternal/paternal derivative chromosomes, reinforcing the hypothesis that human cleavage stage embryogenesis is a cradle of chromosomal rearrangements.
authors.affiliation: Laboratory for Molecular Cytogenetics and Genome Research, Department of Human Genetics, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robberecht
authors.forename: Thierry
authors.initials: T
authors.lastname: Voet
authors.forename: Masoud
authors.initials: M
authors.lastname: Zamani Esteki
authors.forename: Beata A
authors.initials: BA
authors.lastname: Nowakowska
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping; D023281:Genomics; D059765:Homologous Recombination; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D046228:Microarray Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018626:Retroelements; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: D018626:Retroelements