Distal CCAAT box deletion in the A gamma globin gene of two black adolescents with elevated fetal A gamma globin. |
| |
Authors: | J G Gilman N Mishima X J Wen T A Stoming J Lobel T H Huisman |
| |
Affiliation: | Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100. |
| |
Abstract: | Point mutations in G gamma and A gamma globin gene promoters are associated with increased production of G gamma and A gamma globin, respectively. To determine whether an upstream promoter mutation could account for elevated A gamma in a Black adolescent with A gamma-beta+-HPFH and sickle cell trait, we cloned the 13 kb BglII fragment containing both gamma genes into phage lambda vector EMBL3. For one clone, the A gamma upstream promoter showed no hybridization to a 19 bp oligonucleotide whose sequence centered at -117. A gamma promoter sequence data for this mutant clone revealed a 13 bp deletion which eliminated the A gamma distal CCAAT box. Amplified A gamma genomic DNA of this and a similar case showed hybridization to both deletion-mutant and normal oligonucleotide probes. We propose that this 13 bp deletion removes part of the binding site for a repressor protein which is abundant in adult erythroid cells. |
| |
Keywords: | |
|
|