ANALYSIS OF FMR1 AND FLANKING MICROSATELLITE MARKERS IN NORMAL AND FRAGILE-X CHROMOSOMES IN PORTUGAL - EVIDENCE FOR A PROTECTOR HAPLOTYPE

In order to look for linkage disequilibrium between the fragile X locu s and its flanking markers, we analysed the FRAXAC1 and DXS548 microsa tellites in normal and fragile X individuals of Portuguese origin, We observed differences in allele and haplotype frequencies between these two samples, Four haplotypes (A-2, C-2, C-5 and D-6) accounted for 76 % of all fragile X chromosomes, whereas a single haplotype (C-7) accou nted for 70% of the normal population and less than 3% of the fragile X chromosomes, Among the four observed high-risk haplotypes, A-2 and D -6 had been previously reported in other studies, but C-2 and C-5 seem characteristic of Portuguese patients, as suggested by the high frequ ency (38%) in fragile X chromosomes and virtual absence in controls, I n accordance with previous studies, a greater heterozygosity of the fr agile X sample was noted when compared to that of controls, The high f requency of C-7 haplotype in the normal population and its virtual abs ence in the fragile X sample may reflect the existence of linkage dise quilibrium between the two loci and/or selective advantage (protector effect) of this haplotype.