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

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.

FMR1 Linked haplotype analysis in a mentally retarded male population

“…Similar findings, albeit with slightly different frequencies, have been reported from Sweden [27], Czech Republic [28], Finland [30], France [16], Croatia [25], Russia [31], Norway [32] and Poland [29]. In contrast, our finding with respect to the most common allele in FXS patients (allele 2, RF = 0.909) was in agreement with only one of the analyses (Polish population, allele 2; Swedish population, alleles 7 and 6; Czech population, alleles 2, 6 and 7; French population, alleles 2, 6 and 7; Finnish population, almost exclusively allele 6; Croatian population, alleles 7, 6 and 3; Norwegian population, alleles 6 and 2).…”

“…Analysis of this locus in control chromosomes of a Czech population revealed allele 3 to be the most common allele [28]. This was also the case in populations from Russia [31] Norway [32] and Croatia [25], while alleles 3 and 4 were prevalent in a Polish population [29]. Regarding Latvian FXS chromosomes, we found allele 2 to be the most common allele (RF = 0.818).…”

DXS998–DXS548–FRAXAC1 represents a novel informative haplotype at the FMR1 locus in the Iranian population

“…The frequency distribution of the DXS548 alleles was compared with the data from other populations (Chakraborty et al, 2008;Daneberga et al, 2011;Đokic et al, 2008;Drozd et al, 2003b;Felix-López et al, 2006;Haataja et al, 1994;Larsen et al, 2001;Malmgren et al, 1993;Mingroni-Netto et al, 2002;Oudet et al, 1993;Pekarik et al, 1999). Allele 40 at the DXS548 locus was the most common allele (0.69) in the Iranian population which was similar (with slightly different frequencies) to those have been reported from Latvia, Russia, Sweden, Finland, France, Norway, Croatia, Mexico, Brazil, India and Czech Republic.…”

Linkage disequilibrium between microsatellite markers in the Swedish Sami relative to a worldwide selection of populations

“…Their genetic and geographical origin is not established but their ancestors are believed to constitute the first settlers of the Scandinavian Peninsula once the area became accessible after the last Ice Age. Several genetic studies have been carried out to determine the origin of the Sami, by means of protein polymorphisms, mtDNA, Y-chromosome and autosomal markers (Beckman 1996;Larsen et al 2001;Sajantila et al 1995;Tambets et al 2004). These studies indicate that the Sami are genetically distinct but have not provided strong links to other contemporary populations.…”