Distal CCAAT box deletion in the A gamma globin gene of two black adolescents with elevated fetal A gamma globin.
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.
Gilman
J G
JG
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Mishima
N
N
Wen
X J
XJ
Stoming
T A
TA
Lobel
J
J
Huisman
T H
TH
D000293:Adolescent; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002872:Chromosome Deletion; D005319:Fetal Hemoglobin / Q000378:metabolism*; D005914:Globins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012805:Sickle Cell Trait / Q000235:genetics
D005914:Globins; D005319:Fetal Hemoglobin