Haplotype and AGG Interspersion Analysis of FMR1 Alleles in a Croatian Population: No Founder Effect Detected in Patients with Fragile X Syndrome

Abstract

Several studies have suggested that fragile X syndrome (FRAXA), the most common inherited form of mental retardation, originated from a limited number of founder chromosomes. The aim of this study is to assess the genetic origin of fragile X syndrome in a Croatian population. We performed a haplotype analysis of the polymorphic loci DXS548 and FRAXAC1 in 18 unrelated fragile X and 56 control chromosomes. The AGG interspersion pattern of the FMR1 CGG repeat region was analyzed by sequencing. This is the first report on haplotype and AGG interspersion analysis of the fragile X syndrome gene in a Croatian population-the only eastern European population of Slavic origin analyzed so far. Our findings are intriguing, because they show a distinct distribution of the DXS548 and FRAXAC1 alleles in our fragile X population compared to other European fragile X populations. The DXS548/FRAXAC1 haplotype 194/154 (7-3), which is common among normal populations, was found to be the most frequent haplotype in our fragile X population as well. The AGG interspersion analysis indicated that AGG loss rather than haplotype may determine FMR1 allele instability. Our results suggest that no common ancestral X chromosome is associated with fragile X syndrome in the Croatian population studied. Further analysis of the origin of fragile X syndrome among other Slavic populations will be necessary to better define its eastern European distribution.

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.…”

Fragile X Syndrome: The FMR1 CGG Repeat Distribution Among World Populations

“…There is substantial evidence of a strong founder effect in western European populations (Chakravarti, 1992; Richards et al, 1992; Buyle et al, 1993; Oudet et al, 1993b; Malmgren et al, 1994; Chiurazzi et al, 1996b). However, the founder effect is not present in eastern European populations of Slavic origin (Dokić et al, 2008). Within western European populations, significant differences in allelic and haplotypic distributions exist between normal chromosomes found in the general population and chromosomes that harbour the full mutation which causes FXS (Rousseau et al, 1995; Crawford et al, 2001).…”