title: Increased gamma-globin gene expression in beta-thalassemia intermedia patients correlates with a mutation in 3'HS1.
abstract: We report a novel set of genetic markers in the DNaseI hypersensitive sites comprising the human beta-globin locus chromatin hub (CH), namely HS-111 and 3'HS1. The HS-111 (-21 G>A) and 3'HS1 (+179 C>T) transitions form CH haplotypes, which occur at different frequencies in beta-thalassemia intermedia and major patients and normal (nonthalassemic) individuals. We also show that the 3'HS1 (+179 C>T) variation results in a GATA-1 binding site and correlates with increased fetal hemoglobin production in beta-thalassemia intermedia patients. In contrast, the HS-111 (+126 G>A) transition, found in three normal chromosomes, is simply a rare polymorphism. We conclude that the CH haplotypes are useful genetic determinants for beta-thalassemia major and intermedia patients, while the 3'HS1 (+179 C>T) mutation may have functional consequences in gamma-globin genes expression.
authors.affiliation: Department of General Biology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Adamantia
authors.initials: A
authors.lastname: Papachatzopoulou
authors.forename: Polynikis
authors.initials: P
authors.lastname: Kaimakis
authors.forename: Farzin
authors.initials: F
authors.lastname: Pourfarzad
authors.forename: Panagiotis G
authors.initials: PG
authors.lastname: Menounos
authors.forename: Panagiota
authors.initials: P
authors.lastname: Evangelakou
authors.forename: Panagoula
authors.initials: P
authors.lastname: Kollia
authors.forename: Frank G
authors.initials: FG
authors.lastname: Grosveld
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D005914:Globins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin