EXPANSION AND DELETION OF CTG REPEATS FROM HUMAN-DISEASE GENES ARE DETERMINED BY THE DIRECTION OF REPLICATION IN ESCHERICHIA-COLI

Several human hereditary neurological and neurodegenerative disease ge nes are associated with the expansion of CTG repeats. Here we show tha t the frequency of genetic expansions or deletions in Escherichia coli depends on the direction of replication. Large expansions occur predo minantly when the CTGs are in the leading strand template rather than the lagging strand. However, deletions are more prominant when the CTG s are in the opposite orientation. Most deletions generated products o f defined size classes. Strand slippage coupled with non-classical DNA structures may account for these observations and relate to expansion -deletion mechanisms in eukaryotic chromosomes for disease genes.