STABILITY OF TRIPLET REPEATS OF MYOTONIC-DYSTROPHY AND FRAGILE-X LOCIIN HUMAN MUTATOR MISMATCH REPAIR CELL-LINES

At least nine human genetic diseases, including myotonic dystrophy (DM ) and fragile X syndrome have been associated with the expansion of CT G or CGG trinucleotide repeats within the disease loci. Little is know n about the molecular mechanisms or the genetic control of the expansi on of triplet repeats. Mutations in human mismatch repair genes are as sociated with the increased polymorphism of many microsatellites, incl uding dinucleotide repeats. The effect of mutations in two mismatch re pair genes on the size of trinucleotide repeats in the DM and FRAXA lo ci has been analyzed. PCR and Southern analysis of the triplet repeat regions of the DM and fragile X mental retardation (FRAXA) loci in cel l lines HTC116 and LoVo, which contain mutations in both alleles of th e hMLH1 and hMSH2 genes, respectively, indicated that the size of the endogenous (CTG), and (CGG), tracts fall within the range observed in the normal population. This suggests that mutations in hMLH1 or hMSH2 do not result in the instability of CTG or CGG tracts to the levels ob served in individuals with myotonic dystrophy or fragile X syndrome.