Analysis of FMR1 (CGG)(n) alleles and DXS548-FRAXAC1 haplotypes in three European circumpolar populations: traces of genetic relationship with Asia

Fragile X syndrome, the most common form of inherited mental retardation, i s caused by expansion of a (CGG)(n) repeat located in the FMR1 gene. The mo lecular factors involved in the mutation process from stable (CGG)(n) allel es towards unstable alleles are largely unknown, although family transmissi on studies and population studies have suggested that loss of AGG interrupt ions in the (CGG)(n) repeat is essential. We have analysed the AGG interspe rsion pattern of the FMR1 (CGG)(n) repeat and the haplotype distribution of closely located microsatellite markers DXS548 and FRAXAC1, in three circum arctic populations: Norwegians, Nenets and Saami. The data confirm the cons ervation, reported in all human populations studied so far, of an AGG inter ruption for each 9-10 CGG and support the stabilising effect of AGG interru ptions. The data also indicate the existence of chromosomes of Asian origin in the Saami and Nenets population, thereby confirming a genetic relations hip between Northern Europe and Asia. DXS548-FRAXAC1 haplotype frequencies were compared between 24 Norwegian fragile X males and 119 normal males. Si gnificant linkage disequilibrium were found between the fragile X mutation and haplotype 6-4 and between normal (CGG)(n) alleles and haplotype 7-3.