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- Title
Complex Genomic Rearrangements at the PLP1 Locus Include Triplication and Quadruplication.
- Authors
Beck, Christine R.; Carvalho, Claudia M. B.; Banser, Linda; Gambin, Tomasz; Stubbolo, Danielle; Yuan, Bo; 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.
- Subjects
INVERTED repeats (Genetics); PELIZAEUS-merzbacher disease; PROTEOLIPIDS; HUMAN genome; DUCHENNE muscular dystrophy; POINT mutation (Biology)
- Publication
PLoS Genetics, 2015, Vol 11, Issue 3, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1005050