The repeated sequence (AT)x(T)y upstream to the beta-globin gene is a simple polymorphism.

At position 0.5 kb upstream to the &globin gene lies a repeated purine-pyrimidine sequence (AT),(T),, which exhibits a great variation in length and configuration.’ The different specific patterns of this sequence are in strict linkage disequilibrium with the 0-globin haplotype. The (AT)yT5 motif has been identified several years ago in a carrier of silent 0-thalassemia of Albanian descent.’ Later on a number of studies have confirmed the association between the (AT),TS motif and silent 8-thalassemia’ and showed the presence of the same motif in cis to the S mutation in Indian AS heterozygotes, who are characterized by a consistently lower expression of HbS compared with African AS carriers4 The (AT),(T), sequence lies within a negative regulatory region between nucleotides -610 and -490 upstream from the @globin gene and is the binding site for a putative negative regulatory transacting factor called BPl .5 Mobility shift analysis has recently shown that the (AT)+TS motif binds more strongly BPI compared with the reference sequence (AT)7T7, supporting the hypothesis that the (AT)9T, motif produces a very mild /3-thalassemia phenotype.6 In contrast with these conclusions, the (AT)9T5 motif has been detected in a large number of normal individuals of different racial origin.’ However, the normal individuals included in these studies were not analyzed by globin chain synthesis analysis, which is the only method by definition to detect the silent &thalassemia.