Emergence of complex rearrangements at translocation breakpoints in a transgenic mouse; implications for mechanisms involved in the formation of chromosome rearrangements

Abstract

Cryptic complex rearrangements as a result of a reciprocal chromosome translocation have been characterised in a transgenic mouse strain. Analysis of the breakpoint junctions in our previous studies showed that the ada transgene was integrated at the breakpoint forming a fusion gene with Golga3 (Mea2). In this study, further detailed analysis around the translocation junctions revealed that the surrounding regions were composed of 13 fragments of defined transgenic chromosome origins over approximately 1.9-Mb areas. Exactly the same cluster structure of these 13 breakpoint fragments already existed in the second generation of the transgenic mice. Our results show that this highly complex rearrangement has been conserved as the incipient form without any additional changes for 18 years up to the present generation, suggesting simultaneous occurrence of multiple events in the founder mouse.

Characterisation of MutaTMMouse gt10-lacZ transgene: evidence for in vivo rearrangements

“…The transgene copy fusions identified in this study are consistent with complex rearrangements of gene concatemers observed in other transgenic mice (29–32). The fusions could have arisen independently of each other, by either non-homologous end-joining or recombination, as suggested for modifications observed in other types of transgenes after their integration (33,34), or in the case of R2, by sequence degradation due to nuclease ‘nibbling’ (30,35,36).…”

The distribution of cotransformed transgenes in particle bombardment-mediated transformed wheat

“…Transgene integration sites were detected at the border of 1R and 6A chromosomes translocations in line hybrid-A. This is in agreement with the observations that transgene insertion sites are frequently associated with chromosomal rearrangements (Chiang et al 2012;Le Saux et al 2010;Kasai et al 2007). Previous studies indicated that translocation breakpoints were often located at the border of C-bands and the euchromatin region or between two adjacent C-bands in wheat (Taketa and Kawahara 1996;Badaeva et al 2007).…”

Use of microarray hybrid capture and next-generation sequencing to identify the anatomy of a transgene

“…Reported rearrangements include deletions, duplications, inversions and translocations (7–9,13,14) reviewed earlier by Wrutele et al (15). These integrations and rearrangements of genomic structure are of particular interest to the fields of cancer and gene therapy.…”