Polymorphism of Trinucleotide Repeats at Loci FRAXA and FRAXE in the Population of Tomsk

Polymorphism of CGG and GCC trinucleotide repeats, whose expansions at the FRAXA and FRAXE loci have been identified as causative mutations in two forms of mental retardation, was studied in Slavic population of Tomsk. At the FRAXA locus a total of 31 allelic variants ranging from 8 to 56 copies of CGG repeat with two modal classes of 28–29 and 18–20 repeat units (with the frequencies of 24.6 and 11.5% respectively) were revealed. Compared to other populations, this locus was characterized by unusually high frequency of intermediate alleles with the sizes of more than 40 CGG repeat units (12.4%). Since intermediate repeats of the FRAXAlocus were more prone to instability than normal alleles, it was suggested that Slavic population of Siberia had higher risk of the development of FMR1 dynamic mutations, giving rise to the Martin–Bell syndrome. The FRAXE allele frequency distribution was demonstrated to be normal with 18 allelic variants ranging from 9 to 27 GCC repeat units. In the population of Tomsk this locus had higher than in other populations frequency (26.7%) of short (less than 15 repeat units in size) alleles. In addition, in the Tomsk population both loci were characterized by high level of heterozygosity and low frequencies of modal allele classes. These results can be explained by the high level of outbreeding typical of the population of Siberia.