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Dissecting the Structure and Mechanism of a Complex Duplication–Triplication Rearrangement in the DMD Gene
Author(s) -
Ishmukhametova Aliya,
Chen JianMin,
Bernard Rafaëlle,
Massy Bernard,
Baudat Frédéric,
Boyer Amandine,
Méchin Déborah,
Thorel Delphine,
Chabrol Brigitte,
Vincent MarieClaire,
Khau Van Kien Philippe,
Claustres Mireille,
TufferyGiraud Sylvie
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22353
Subject(s) - gene duplication , tandem exon duplication , biology , genetics , gene rearrangement , segmental duplication , exon , chromosomal rearrangement , inverted repeat , gene , breakpoint , dup , chromosome , genome , gene family , karyotype
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 PRDM 9 binding site in the near vicinity of the junction involving two inverted L 1 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.