Is there a common pathogenic pathway in the dynamic mutation diseases?
Several human genetic diseases are thought to be caused by polyglutamine repeats that expand in copy number beyond a threshold (e.g. Huntington’s disease). There are, however, numerous other neurodegenerative diseases that have very similar clinical symptoms to the polyglutamine diseases and are due to expanded repeats, but these repeats cannot encode polyglutamine. We have therefore used transgenic Drosophila models of these repeat expansion diseases in order to test hypotheses in regard to whether there might be common pathogenic pathways for dynamic mutation diseases.We have specifically assessed 1) whether RNA might be the pathogenic agent [as has been shown for CUG expansion in myotonic dystrophy] 2) whether polyalanine might be the common agent (by virtue of frameshift slippage) 3) whether apoptosis initiated by DNA breakage of the expanded repeat (as is seen for rare chromosomal fragile sites) might be the common pathogenic pathway.In each case the transgenic Drosophila analysis
