MOLECULAR-BASIS OF P(CCG)N REPEAT INSTABILITY AT THE FRA16A FRAGILE SITE LOCUS

Rare, folate-sensitive fragile sites are the result of the unstable ex pansion of trinucleotide p(CCG)n repeats, which are normally polymorph ic in copy number. Differences in the number and frequency of alleles of the fragile site FRA16A p(CCG)n repeat were observed between differ ent ethnic populations suggesting that certain alleles might be predis posed to instability. Sequence analysis demonstrated that the longer a nd more variable alleles were associated with loss of repeat interrupt ion. Perfect repeat configuration therefore appears to be a necessary precondition for the instability associated with fragile site genesis.