Fragile X founder effects in Argentina

Abstract

To investigate the origin of fragile X mutations in the Argentine population, we studied the alleles and haplotypes at DXS548 and FRAXAC1 loci of 42 unrelated fragile X chromosomes and 168 normal ones. Four haplotypes presented in linkage disequilibrium and accounted for 76.2% of fragile X chromosomes, representing the high frequency of haplotype DXS548-FRAXAC1 7-1 (26.2%) characteristic of our population. FRAXAC1 allele 1 was observed on 47.6% of fragile X chromosomes. Thus, we provide evidence for fragile X founder effects in the Argentine population, similar to those observed in Caucasians and in Asians.

Haplotype analysis at the FRAXA locus in Thai subjects

“…Interestingly, of 14 haplotypes in the FXS group, 6 haplotypes were not found in the control group possibly suggesting either new mutations or admixture of immigrant haplotypes. Our ®ndings apparently contrast with most other reports on FXS founder effects in different ethnic groups [Richards et al, 1992Jacobs et al, 1993;Buyle et al, 1993;Hirst et al, 1993;Haataja et al, 1994;Macpherson et al, 1994;Zhong et al, 1994aZhong et al, , 1994bZhong et al, , 1996aZhong et al, , 1999Syrrou et al, 1996;Chiurazzi et al, 1996aChiurazzi et al, , 1996bChiurazzi et al, , 1996cFalik-Zaccai et al, 1997;Bonaventure et al, 1998;Pekarõ Ák et al, 1999;Mingroni-Netto et al, 1999]. There was only one report [Pesso et al, 1997] showing no founder effects in a speci®c ethnic population, that of Ashkenazi Jews.…”

“…This ®nding suggests that the evolution of Thai FXS mutation may be different as compared to other ethnic groups. Likewise, a rare haplotype, 20±21, was commonly found in Argentine founder FXS chromosomes [Bonaventure et al, 1998]. Analysis of the SNP (ATL1-IVS10) haplotypes showed the A-C haplotype was seen in excess in the 30 CGG repeat group.…”

“…In our experience, approximately 7% of Thai samples referred for FXS testing show positive results on molecular analysis [Limprasert et al, 1999a]. Previous studies have investigated haplotype associations using microsatellites near the FMR1 gene in various populations: Australian [Richards et al, 1992], British [Jacobs et al, 1993;Macpherson et al, 1994], White American [Zhong et al, 1994a, Belgian±Dutch [Buyle et al, 1993, Finn [Haataja et al, 1994;Zhong et al, 1996a], Swedish [reviewed by Chiurazzi et al, 1996a], Italian [Chiurazzi et al, 1996b], Jewish [Pesso et al, 1997;Falik-Zaccai et al, 1997], Sub-Saharah African [Chiurazzi et al, 1996c], Greek±Cyprian [Syrrou et al, 1996], Czech [Pekarõ Ák et al, 1999], Argentine [Bonaventure et al, 1998], Brazilian [Mingroni-Netto et al, 1999], Japanese and Chinese [Zhong et al, 1994b;Zhong et al, 1999]. In these reports, it is apparent that although FXS chromosomes are associated with several haplotypes, only a few account for most of the total, with a distribution signi®cantly different from that of normal controls.…”

AGG interspersion patterns in the CGG repeat of the FMR1 gene and linked DXS548/FRAXAC1 haplotypes in Brazilian populations

“…It was less frequent in Sã o Paulo city (1.8%, present study and 8.3%, Mingroni-Netto et al, 2002]. This is not a rare haplotype in populations hereto studied [Chiurazzi et al, 1996;Bonaventure et al, 1998;Jara et al, 1998;Peixoto et al, 1998;Mingroni-Netto et al, 1999;Patsalis et al, 1999;Pekarík et al, 1999;Poon et al, 1999;Limprasert et al, 2001], and only a fraction of linked CGG alleles shows AGG interspersion patterns that would predis-pose to large expansions [Hirst et al, 1993;Kunst and Warren, 1994;Eichler et al, 1996;Crawford et al, 2000a;Sullivan et al, 2002]. The eight CGG alleles from African-Brazilians linked to haplotype 6-4 neither had a long CGG array nor long uninterrupted tracts.…”