Cloned human FMR1 trinucleotide repeats exhibit a length- and orientation-dependent instability suggestive of in vivo lagging strand secondary structure

摘要: The normal human FMR1 gene contains a genetically stable (CGG) n trinucleotide repeat which usually carries interspersed AGG triplets. An increase in number and the loss of interspersions results array instability, predominantly expansion, leading to silencing. Instability is directly related length uninterrupted widely assumed be an increased propensity form G-rich secondary structures lead expansion through replication slippage. In order investigate this we have cloned arrays with internal representing normal, intermediate unstable states. one replicative orientation, show length-dependent deletions occurring polar manner. With longer these extend into 5'-flanking DNA, terminating at either two short CGG triplet arrays. orientation-dependent instability suggests that structure forms lagging strand template, resolution intra-array deletion. These data provide direct vivo evidence for believed involved process humans.