Haplotype analysis at the FRAXA locus in Thai subjects

Abstract

The prevalence of fragile X syndrome (FXS) is approximately 7% in Thai boys with developmental delay of unknown cause. To determine if FXS might have a specific haplotype association, we analyzed 125 unrelated control subjects and 25 unrelated FXS patients using 3 microsatellites, DXS548, FRAXAC1 and FRAXE, and two single nucleotide polymorphisms, ATL1 and IVS10. FRAXAC1 and DXS548 are located approximately 7 kb and approximately 150 kb proximal to the CGG-FMR1 whereas ATL1, IVS10 and FRAXE are located approximately 5.6 kb, approximately 24.5 kb and approximately 600 kb distal to the CGG-FMR1. We found 40 haplotypes in the control group and 14 haplotypes in the FXS group. Of 14 haplotypes in the FXS group, 6 haplotypes were not found in the control group suggesting possible new mutations or admixture of immigrant haplotypes. We observed that most diverse haplotypes came from different FRAXE alleles. For this reason, we analyzed haplotypes composed from the remaining markers alone (DXS548-FRAXAC1-ATL1-IVS10). We found 2 major haplotypes (20-18-G-T and 20-19-A-C) with no significant haplotype differences between the control group (67/125 of 20-18-G-T and 25/125 of 20-19-A-C) and FXS group (16/25 of 20-18-G-T and 6/25 of 20-19-A-C). The other haplotypes found were 33/125 in the control group and 3/25 in the FXS group. The two major haplotypes associated FXS in Thai subjects were the two most common haplotypes in the normal Thai subjects. We could not prove, therefore, that there were founder effects at the FRAXA locus in Thailand. We could not, however, exclude it completely. These findings apparently contrast with most other reports on FXS founder effects in various ethnic groups.

Distribution of fragile X mental retardation 1 CGG repeat and flanking haplotypes in a large Chinese population

“…The most frequent alleles for DXS548 and FRAXAC1 were identical among our Chinese population, previous Chinese samples, and other Asians such as Indonesian, Japanese, and Thai (Richards et al 1994;Zhong et al 1999;Faradz et al 2000;Limprasert et al 2001;Tzeng et al 2005). The distributions for both the CGG repeat lengths and patterns in the Chinese population share similarities to that in Singaporeans (Zhou et al 2006).…”

“…They also examined the CGG repeat size and flanking haplotypes (DXS548-FRAXAC1-FRAXAC2) in 637 unaffected and 63 fragile X African Americans, along with 721 unaffected and 102 fragile X Caucasians (Crawford et al 2000a). Haplotype (DXS548-FRAXAC1) analysis has been performed in mainland Chinese (n = 206), Taiwanese (n = 100), Hong Kongers (n = 217), Thais (n = 125), and Indonesians (n = 1043), together with fragile X patients from mainland China (n = 24), Taiwan (n = 28), and Thailand (n = 25) (Poon et al 1999;Zhong et al 1999;Faradz et al 2000;Limprasert et al 2001;Tzeng et al 2005). Studies have been conducted to evaluate the CGG repeat patterns in Japanese (n = 21), Asians (n = 144), and Taiwanese (n = 78) (Chen et al 1997;Hirst et al 1997;Chiu et al 2008).…”

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.…”

Haplotype analysis at the FRAXA locus in an Indian population

“…The increase of heterozygosities in fragile X samples (DXS548 67.5%, FRAXAC1 62.8%, FRAXAC2 68.5%) relative to the controls (DXS548 63.3%, FRAXAC1 51%, FRAXAC2 67.2%) have been observed in all the three tested marker loci. The increase of heterozygosity in fragile X patients have been observed in almost every population studied [Zhong et al, 1994; Bonaventure et al, 1998; Pekarik et al, 1999; Limprasert et al, 2001] and this reflects multimodal distribution of the fragile X associated alleles and the presence of one dominant allele in the controls. We also found that heterozygosity of all markers was higher in fragile X samples in comparison to the normal controls.…”