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

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, FRAXAC1 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. Heredity (2003) 90, 206‐211. doi:10.1038/sj.hdy.6800218