Abstract
Fragile X syndrome, the most common form of inherited mental retardation, is caused by expansion of a (CGG)n repeat located in the FMR1 gene. The molecular factors involved in the mutation process from stable (CGG)n alleles towards unstable alleles are largely unknown, although family transmission studies and population studies have suggested that loss of AGG interruptions in the (CGG)n repeat is essential. We have analysed the AGG interspersion pattern of the FMR1 (CGG)n repeat and the haplotype distribution of closely located microsatellite markers DXS548 and FRAXAC1, in three circumarctic populations: Norwegians, Nenets and Saami. The data confirm the conservation, reported in all human populations studied so far, of an AGG interruption for each 9–10 CGG and support the stabilising effect of AGG interruptions. The data also indicate the existence of chromosomes of Asian origin in the Saami and Nenets population, thereby confirming a genetic relationship between Northern Europe and Asia. DXS548-FRAXAC1 haplotype frequencies were compared between 24 Norwegian fragile X males and 119 normal males. Significant linkage disequilibrium were found between the fragile X mutation and haplotype 6-4 and between normal (CGG)n alleles and haplotype 7-3.
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Acknowledgements
We would like to thank Mads Dahm Johansen for excellent technical assistance. We would also like to acknowledge the initial work done by Umayal Rubenthiran and extremely valuable ideas and discussions along the way with senior scientist, PhD Øivind Nilssen, Department of Medical Genetics, University Hospital, Tromsø, Norway. Ethical approval of the Russian part of the study was given by the Arkhangelsk State Medical Academy, Russia.
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Larsen, L., Vuust, J., Nystad, M. et al. Analysis of FMR1 (CGG)n alleles and DXS548-FRAXAC1 haplotypes in three European circumpolar populations: traces of genetic relationship with Asia. Eur J Hum Genet 9, 724–727 (2001). https://doi.org/10.1038/sj.ejhg.5200697
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DOI: https://doi.org/10.1038/sj.ejhg.5200697
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