Functional role of a delta globin gene promoter mutation

• Main Author: Nwaru, Maxwell Ibeabuchi Jr.
• Language: en_US
• Published: Boston University 2015
• Online Access: https://hdl.handle.net/2144/12544

Thesis (M.A.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [e-mail]. Thank you. === In patients with sickle cell disease (SCD), the levels of fetal hemoglobin (HbF) in circulation can be a major modulator of the disease. The concentrations of HbF found in SCD patients may vary as a result of genetic variations that can be marked by single nucleotide polymorphisms (SNPs). Saudi Arabian patients with the Arab-Indian (AI) haplotype of the β-globin gene cluster have significantly higher levels of HbF. In order to identify the molecular mechanism responsible for high HbF expression, the β-globin gene cluster of these patients was extensively sequenced. We identified a SNP , -68 base pairs 5', to the δ-globin gene (HBD). Accordingly, to assign a functional role to this SNP , we transfected the -68 HBD promoter into K562 cells and compared its expression to that of the normal HBD promoter. The -68 C>T SNP was associated with downregulation of HBD promoter expression in K562 cells. We also studied the effect of butyrate on the expression of transfected HBD promoters and it appears that butyrate inhibits the expression of normal HBD promoter but not the mutant promoter. The -68 C>T polymorphism is likely to be functional and could downregulate HBD expression. Whether or not this has a role in increasing HbF expression in the AI haplotype of SCD is unknown.