Evidence for high-risk haplotypes and (CGG)n expansion in fragile X syndrome in the Hellenic population of Greece and Cyprus

Syrrou, Maria; Patsalis, Philippos C.; Georgiou, Ioannis; Hadjimarcou, Michael I.; Constantinou-Deltas, C. D.; Pagoulatos, Gerassimos N.

doi:10.1002/(sici)1096-8628(19960712)64:1<234::aid-ajmg42>3.0.co;2-l

Cited by 17 publications

(14 citation statements)

References 17 publications

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“…The distribution of CGG repeats was similar to the general Basque sample from Biscay previously analyzed, and the same mode as in other European populations was observed (Macpherson et al, 1994;Chiurazzi et al, 1996a;Syrrou et al, 1996;Zhong et al, 1996;Arrieta et al, 1999b;Patsalis et al, 1999;Larsen et al, 2000).…”

Section: Arrieta Et Alsupporting

confidence: 84%

The FMR1 CGG repeat and linked microsatellite markers in two Basque valleys

et al. 2003

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Fragile X syndrome is associated with an unstable CGG repeat sequence in the 5 0 untranslated region of the first exon of the FMR1 gene. The present study involved the evaluation of factors implicated in CGG repeat stability in a normal sample from two Basque valleys (Markina and Arratia), to discover whether the Basque population shows allelic diversity and to identify factors involved, by using the data in conjunction with previous findings. The study was based on a sample of 204 and 58 X chromosomes from the Markina and Arratia valleys, respectively. The CGG repeat, the AGG interspersion and two flanking microsatellite markers, FRAX-AC1 and DXS548, were examined. In the Markina valley, gray zone alleles (X35 CGG repeats) were associated with anchoring AGGs, with the longest 3 0 pure CGG repeats of the valley ( ¼ 15), with the 5 0 instability structure 9+n and with one principal fragile X FRAXAC1-DXS548 haplotype 42-50. In the Arratia valley, gray zone alleles (X35 CGG repeats) showed the highest frequency among the Basque samples analyzed, and were associated with anchoring AGGs, with the longest 3 0 pure repeats (X20), with the 5 0 instability structure 9+n and with one 'normal' FRAXAC1-DXS548 haplotype 38-40 (these data from Arratia suggest the existence of a 'protective' haplotype). The results showed, on the one hand, differences between Markina and Arratia in factors implicated in CGG repeat instability and, on the other hand, a great similarity between the general Basque sample from Biscay and the Markina valley.

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Section: Arrieta Et Alsupporting

confidence: 84%

The FMR1 CGG repeat and linked microsatellite markers in two Basque valleys

et al. 2003

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“…Our population reveals a high prevalence of the FRAXAC1-3 allele among the fragile X cohort also, a finding similar to that seen among the Finns and the Danes (Zhong et al 1996;Larsen et al 2000). (4) A new allele (designated -5) at the FRAXAC2 locus has been identified in our study sample.However, allele frequency distribution at this locus in our nonfragile X controls showed an overall similarity to Western Caucasian (Australia, Europe, and North America) and African-American populations with FRAXAC2-4+ being the most frequent allele Haataja et al 1994;Macpherson et al 1994;Rousseau et al 1995;Syrrou et al 1996;Crawford et al 2000). The Japanese population, the only other Asian population evaluated for polymorphism at this locus, however revealed a dis-tinct modal allele (FRAXAC2-6+) (Richards et al 1994).…”

Section: Discussionsupporting

confidence: 49%

“…Allele frequency distributions at these polymorphic loci have been investigated among control and fragile X chromosomes from diverse ethnic populations worldwide (Haataja et al 1994;Macpherson et al 1994;Richards et al 1994;Syrrou et al 1996;Bonaventure et al 1998;Zhong et al 1999;Crawford et al 2000). However, the majority of these studies have been limited to the Western (White) Caucasian ethnic groups derived primarily from North America, Europe and Australia.…”

Section: Introductionmentioning

confidence: 99%

FMR1 haplotype analyses among Indians: a weak founder effect and other findings

2002

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This study on allelic/haplotypic fragile X associations evaluated using STR (DXS548, FRAXAC1, FRAXAC2) and SNP (ATL1) markers flanking the (CGG) n locus of FMR1 is the first report from the large ethnically complex Indian population. Results have been compared with allele/haplotype distributions reported for other major ethnic groups, including White Caucasians, Africans, and Pacific Asians. Though overall allele frequency distributions at the individual loci are more similar to Western Caucasians compared with others, significant differences are observed in haplotypic associations with the mutated X. The striking findings are: (1) high diversity and heterozygosity of haplotypes among fragile X chromosomes (n=40) and controls (n=262), including four haplotypes found exclusively in this study sample;(2) weak association of DXS548-FRAXAC1-FRAXAC2 haplotypes, 2-1-3, 6-3-3+ and 7-4-6+ with the disorder, and absence of White Caucasian fragile X haplotypes 6-4-4 and 6-4-5; (3) weak founder effect for the fragile X expansion mutation in the Indians; (4) lack of a continuum of haplotype-based FMR1 alleles between intermediate (CGG) n size ranges and expanded alleles; (5) exclusion of ATL1 as a candidate genetic indicator of FMR1 instability. The high STR-based haplotype diversity observed among fragile X lineages, irrespective of ethnic alliances, strongly suggests the inappropriateness of using STR haplotypes to infer predisposition to instability among ethnically separated fragile X pedigrees and may reiterate the need for identifying newer SNPs from this region to not only determine true founder effects for the fragile X mutation, but also decipher possible mechanisms leading to CGG instability.

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“…In addition, the genetic isolation level appears as an important factor influencing the strength of association. Thus, in the isolated Finnish population 75% of all fragile X chromosomes were linked to a single rare haplotype [Oudet et al, 1993b;Haataja et al, 1994;Zhong et al, 1996], whereas the Greek population showed no particular haplotypes in disequilibrium, possibly as a result of its heterogeneous genetic history [Syrrou et al, 1996].…”

Section: Introductionmentioning

confidence: 96%

Fragile X founder effects in Argentina

et al. 1998

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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.

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Evidence for high-risk haplotypes and (CGG)n expansion in fragile X syndrome in the Hellenic population of Greece and Cyprus

Cited by 17 publications

References 17 publications

The FMR1 CGG repeat and linked microsatellite markers in two Basque valleys

The FMR1 CGG repeat and linked microsatellite markers in two Basque valleys

FMR1 haplotype analyses among Indians: a weak founder effect and other findings

Fragile X founder effects in Argentina

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