title: Dissecting the structure and mechanism of a complex duplication-triplication rearrangement in the DMD gene.
abstract: Pathogenic complex genomic rearrangements are being increasingly characterized at the nucleotide level, providing unprecedented opportunities to evaluate the complexities of mutational mechanisms. Here, we report the molecular characterization of a complex duplication-triplication rearrangement involving exons 45-60 of the DMD gene. Inverted repeats facilitated this complex rearrangement, which shares common genomic organization with the recently described duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) events; specifically, a 690-kb region comprising DMD exons from 45 to 60 was duplicated in tandem, and another 46-kb segment containing exon 51 was inserted inversely in between them. Taking into consideration (1) the presence of a predicted PRDM9 binding site in the near vicinity of the junction involving two inverted L1 elements and (2) the inherent properties of X-Y chromosome recombination during male meiosis, we proposed an alternative two-step model for the generation of this X-linked DMD DUP-TRP/INV-DUP event.
authors: Université Montpellier 1, UFR médecine, Montpellier F-34000, France. aliya.ishmukhametova@inserm.fr
authors: Aliya
authors: A
authors: Ishmukhametova
authors: Jian-Min
authors: JM
authors: Chen
authors: Rafaëlle
authors: R
authors: Bernard
authors: Bernard
authors: B
authors: de Massy
authors: Frédéric
authors: F
authors: Baudat
authors: Amandine
authors: A
authors: Boyer
authors: Déborah
authors: D
authors: Méchin
authors: Delphine
authors: D
authors: Thorel
authors: Brigitte
authors: B
authors: Chabrol
authors: Marie-Claire
authors: MC
authors: Vincent
authors: Philippe
authors: P
authors: Khau Van Kien
authors: Mireille
authors: M
authors: Claustres
authors: Sylvie
authors: S
authors: Tuffery-Giraud
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D053960:DNA Breaks; D056915:DNA Copy Number Variations; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D020440:Gene Duplication; D014644:Genetic Variation; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D055029:Inverted Repeat Sequences; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism; D057345:Sequence Inversion
chemical_list: C484258:DMD protein, human; D016189:Dystrophin; D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human
keywords: DMD; PRDM9; complex rearrangements; inverted repeats