A complex mutable polymorphism located within the fragile X gene

Abstract
While studying founder chromosomes in the fragile X syndrome, we have unexpectedly found linkage equilibrium to FRAXAC2, an Alu–associated microsatellite within the defective gene, FMR–1. DNA sequencing of 265 chromosomes revealed 39 alleles and a complex microsatellite of form (GT)x–C–(TA)y–(T)z. A mutation rate of 3.3% was observed but only among fragile X maternally derived meioses. Finding a second mutable locus within FMR–1 suggests that the target for tandem repeat instability may not be confined to the (CGG)nrepeat alone and raises the possibility of an FMR–1 mutation mechanism involving microsatellites.