| Abstrakt: |
Duchenne muscular dystrophy is an inherited muscle wasting disease with severe symptoms and onset in early childhood. Duchenne muscular dystrophy is caused by loss-of-function mutations, most commonly deletions, within the DMD gene. Characterizing the junction points of large genomic deletions facilitates a more detailed model of the origins of these mutations and allows for a greater understanding of phenotypic variations associated with particular genotypes, potentially providing insights into the deletion mechanism. Here, we report sequencing of breakpoint junctions for seven patients with intragenic, whole-exon DMD deletions. Of the seven junction sequences identified, we found one instance of a "clean" break, three instances of microhomology (2–5 bp) at the junction site, and three complex rearrangements involving local sequences. Bioinformatics analysis of the upstream and downstream breakpoint regions revealed a possible role of short inverted repeats in the initiation of some of these deletion events. Duchenne muscular dystrophy: Understanding how the DMD gene breaks Researchers in Australia have identified new examples of the genomic factors and mechanisms that lead to deletions linked with Duchenne muscular dystrophy (DMD). DMD is an inherited neuromuscular disease which causes progressive deterioration of muscles and, in some cases, intellectual impairment. Using samples from seven DMD patients, Niall Keegan of Murdoch University in Perth and colleagues sequenced the DNA left behind around the deletions in the DMD gene which cause the disease. They found one clean break, three sections with short repeated sequences, and three with more complex rearrangements. The diversity of these findings led them to suggest that the deletions resulted from a diversity of genomic factors and repair mechanisms. Future work could incorporate these findings into a model to predict where deletions will occur, expanding our understanding of DMD and its causes. [ABSTRACT FROM AUTHOR] |
Full text from SpringerLink