We analyzed the FRAXAC2 and DXS548 microsatellites in normal and fragile X chromosomes from Sweden and the Czech Republic in order to investigate a possible founder effect for chromosomes carrying a fragile X mutation. We report a much stronger linkage disequilibrium between the marker haplotypes and the disease in Swedish fragile X chromosomes than in Czech and most other previously studied Caucasian populations. Two haplotypes accounted for 64% of Swedish fragile X chromosomes and for only 14% of normal chromosomes. Neither of these two haplotypes was found in Czech chromosomes, but the most common Swedish fragile X haplotype is the same as that reported to be predominant in Finnish fragile X patients. Linkage disequilibrium was observed in the Czech fragile X chromosomes but the haplotypes were more diverse and similar to those observed in other Caucasian populations. The most prevalent Swedish fragile X haplotype was traced back from affected males to common ancestors in the early 18th century. This indicates an apparently silent segregation of fragile X alleles through up to nine generations. The geographical distribution of the two major at-risk haplotypes in Sweden suggests that they were present among early settlers in different parts of the country.

Department of Medical Genetics University of Uppsala Sweden

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