Evidence for high-risk haplotypes and (CGG)n expansion in fragile X syndrome in the Hellenic population of Greece and Cyprus.
The expansion of the trinucleotide repeat (CGG)n in successive generations through maternal meiosis is the cause of fragile X syndrome. Analysis of CA repeat polymorphisms flanking the FMR-1 gene provides evidence of a limited number of "founder" chromosomes and predisposing high-risk haplotypes related to the mutation. To investigate the origin of mutations in the fragile X syndrome in the Hellenic populations of Greece and Cyprus, we studied the alleles and haplotypes at DXS548 and FRAXAC2 loci of 16 independent fragile X and 70 normal control chromosomes. In addition, we studied 191 unrelated normal X chromosomes for the distribution and frequencies of CGG alleles. At DXS548, 6 alleles were found, 2 (194 and 196) of which were represented on fragile X chromosomes. At FRAXAC2, 6 alleles were found, 4 of which were present on fragile X chromosomes. Sixteen haplotypes were identified, but only 5 were present on fragile X chromosomes. The highest number of CGG repeats (> or = 33) were associated with haplotypes 194-147, 194-151, 194-153, and 204-155. The data provide evidence for founder chromosomes and high-risk haplotypes in the Hellenic population.
Syrrou
M
M
Laboratory of General Biology, Medical School, University of Ioannina, Greece.
Patsalis
P C
PC
Georgiou
I
I
Hadjimarcou
M I
MI
Constantinou-Deltas
C D
CD
Pagoulatos
G
G
D003535:Cyprus; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D005819:Genetic Markers; D006115:Greece; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D012306:Risk; D018911:Trinucleotide Repeats
D005819:Genetic Markers