title: 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.
abstract: Nucleotide sequence analysis of the 5' beta-globin gene flanking region has been carried out for numerous homozygous beta-thalassemia patients with different mutations and of various ethnic backgrounds. Four different rearrangements were found associated with numerous beta-thalassemia 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) chromosomes and the two with the -87 (C-->G) mutation are associated with the (AT)9(T)5 rearrangement, while the 30 IVS-I-6 (T-->C), the 16 codon 39 (C-->T), the six codon 8 (-AA) chromosomes, and 12 chromosomes with different promoter mutations had the (AT)7(T)7 motif. Six chromosomes with the promoter mutation at position -29 (A-->G) had the (AT)8(T)6 motif, while an (AT)8(T)4 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 fetal hemoglobin (Hb F)] levels could be demonstrated, suggesting that variations in the (AT)X(T)Y motif are common polymorphisms.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: A J
authors.initials: AJ
authors.lastname: Dimovski
authors.forename: A D
authors.initials: AD
authors.lastname: Adekile
authors.forename: V
authors.initials: V
authors.lastname: Divoky
authors.forename: E
authors.initials: E
authors.lastname: Baysal
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000328:Adult; D001483:Base Sequence; D003062:Codon; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism; D005914:Globins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D005914:Globins; D005319:Fetal Hemoglobin