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Increased γ‐globin gene expression in β‐thalassemia intermedia patients correlates with a mutation in 3′HS1
Author(s) -
Papachatzopoulou Adamantia,
Kaimakis Polynikis,
Pourfarzad Farzin,
Menounos Panagiotis G.,
Evangelakou Panagiota,
Kollia Panagoula,
Grosveld Frank G.,
Patrinos George P.
Publication year - 2007
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20979
Subject(s) - intermedia , haplotype , thalassemia , biology , fetal hemoglobin , locus (genetics) , genetics , microbiology and biotechnology , globin , hemoglobinopathy , gene , hemoglobin , mutation , transition (genetics) , hemolytic anemia , allele , fetus , immunology , biochemistry , pregnancy , art , performance art , art history
We report a novel set of genetic markers in the DNaseI hypersensitive sites comprising the human β‐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 β‐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 β‐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 β‐thalassemia major and intermedia patients, while the 3′HS1 (+179 C>T) mutation may have functional consequences in γ‐globin genes expression. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.