Complex Genomic Rearrangements at the PLP1 Locus Include Triplication and Quadruplication

2015 | journal article. A publication with affiliation to the University of Göttingen.

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​Complex Genomic Rearrangements at the PLP1 Locus Include Triplication and Quadruplication​
Beck, C. R.; Carvalho, C. M. B.; Banser, L.; Gambin, T.; Stubbolo, D.; Yuan, B. O. & Sperle, K. et al.​ (2015) 
PLoS Genetics11(3) art. e1005050​.​ DOI: https://doi.org/10.1371/journal.pgen.1005050 

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Authors
Beck, Christine R.; Carvalho, Claudia M. B.; Banser, Linda; Gambin, Tomasz; Stubbolo, Danielle; Yuan, B. O.; Sperle, Karen; McCahan, Suzanne M.; Henneke, Marco; Seeman, Pavel; Garbern, James Y.; Hobson, Grace M.; Lupski, James R.
Abstract
Inverted repeats (IRs) can facilitate structural variation as crucibles of genomic rearrangement. Complex duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) rearrangements that contain breakpoint junctions within IRs have been recently associated with both MECP2 duplication syndrome (MIM#300260) and Pelizaeus-Merzbacher disease (PMD, MIM#312080). We investigated 17 unrelated PMD subjects with copy number gains at the PLP1 locus including triplication and quadruplication of specific genomic intervals-16/17 were found to have a DUP-TRP/INV-DUP rearrangement product. An IR distal to PLP1 facilitates DUP-TRP/INV-DUP formation as well as an inversion structural variation found frequently amongst normal individuals. We show that a homology-or homeology-driven replicative mechanism of DNA repair can apparently mediate template switches within stretches of microhomology. Moreover, we provide evidence that quadruplication and potentially higher order amplification of a genomic interval can occur in a manner consistent with rolling circle amplification as predicted by the microhomology-mediated break induced replication (MMBIR) model.
Issue Date
2015
Status
published
Publisher
Public Library Science
Journal
PLoS Genetics 
ISSN
1553-7404; 1553-7390

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