POLYMORPHIC PATTERN OF THE (AT)X(T)Y MOTIF AT - 530 5' TO THE BETA-GLOBIN GENE IN OVER 40 PATIENTS HOMOZYGOUS FOR VARIOUS BETA-THALASSEMIA MUTATIONS

Nucleotide sequence analysis of the 5' beta-globin gene flanking regio n has been carried out for numerous homozygous beta-thalassemia patien ts with different mutations and of various ethnic backgrounds. Four di fferent rearrangements were found associated with numerous beta-thalas semia mutations. The (AT)X(T)Y repeat motif at -530 showed polymorphic patterns among these patients as follows: All ten IVS-II-1 (G-->A) ch romosomes and the two with the -87 (C-->G) mutation are associated wit h the (AT)9(T)5 rearrangement, while the 30 IVS-I-6 (T-->C), the 16 co don 39 (C-->T), the six codon 8 (-AA) chromosomes, and 12 chromosomes with different promoter mutations had the (AT)7(T)7 Motif. Six chromos omes with the promoter mutation at position 29(A-->G) had the (AT)8(T) 6 motif, while an (AT)8(T), motif appears characteristic for two IVS-I -5(G-->A and G-->T). No direct association between any of the (AT)X(T) Y arrangements and an increased gamma gene expression [(G)gamma and fe tal hemoglobin (Hb F)] levels could be demonstrated, suggesting that v ariations in the (AT)X(T)Y motif are common polymorphisms. (C) 1994 Wi ley-Liss, Inc.