Dissecting the Structure and Mechanism of a Complex Duplication-Triplication Rearrangement in theDMDGene
- 6 May 2013
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 34 (8), 1080-1084
- https://doi.org/10.1002/humu.22353
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.This publication has 16 references indexed in Scilit:
- Inverted Low-Copy Repeats and Genome Instability-A Genome-Wide AnalysisHuman Mutation, 2012
- The tricky path to recombining X and Y chromosomes in meiosisAnnals of the New York Academy of Sciences, 2012
- Comprehensive oligonucleotide array-comparative genomic hybridization analysis: new insights into the molecular pathology of the DMD geneEuropean Journal of Human Genetics, 2012
- Aberrant firing of replication origins potentially explains intragenic nonrecurrent rearrangements within genes, including the human DMD geneGenome Research, 2011
- Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genomeNature Genetics, 2011
- On the sequence-directed nature of human gene mutation: The role of genomic architecture and the local DNA sequence environment in mediating gene mutations underlying human inherited diseaseHuman Mutation, 2011
- Fine-scale recombination rate differences between sexes, populations and individualsNature, 2010
- PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humansNature Genetics, 2010
- Genomic rearrangements in inherited disease and cancerSeminars in Cancer Biology, 2010
- PRDM9 Is a Major Determinant of Meiotic Recombination Hotspots in Humans and MiceScience, 2010