Complex genomic rearrangements at the PLP1 locus include triplication and quadruplication.
PLoS Genet
; 11(3): e1005050, 2015 Mar.
Article
en En
| MEDLINE
| ID: mdl-25749076
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína Proteolipídica de la Mielina
/
Duplicación de Gen
/
Enfermedad de Pelizaeus-Merzbacher
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article