Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations

Caroline Robberecht; Thierry Voet; Masoud Zamani Esteki; Beata A. Nowakowska; Joris R. Vermeesch

doi:10.1101/gr.145631.112

Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations

¹Laboratory for Molecular Cytogenetics and Genome Research,
²Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Herestraat 49, 3000 Leuven, Belgium

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.

Footnotes

↵3 Corresponding author

E-mail Joris.Vermeesch{at}uzleuven.be
[Supplemental material is available for this article.]
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.145631.112.

Received July 9, 2012.
Accepted November 21, 2012.

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