title: Strong founder effect for the fragile X syndrome in Sweden.
abstract: 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.
authors.affiliation: Department of Medical Genetics, University of Uppsala, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Malmgren
authors.forename: K H
authors.initials: KH
authors.lastname: Gustavson
authors.forename: C
authors.initials: C
authors.lastname: Oudet
authors.forename: G
authors.initials: G
authors.lastname: Holmgren
authors.forename: U
authors.initials: U
authors.lastname: Pettersson
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D016009:Chi-Square Distribution; D018153:Czech Republic / Q000453:epidemiology; D004276:DNA, Satellite / Q000032:analysis; D005600:Fragile X Syndrome / Q000453:epidemiology* / Q000235:genetics*; D005787:Gene Frequency; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D017720:Molecular Epidemiology; D010375:Pedigree; D013548:Sweden / Q000453:epidemiology
chemical_list: D004276:DNA, Satellite