Concordance of a point mutation 5' to the A gamma-globin gene with A gamma beta + hereditary persistence of fetal hemoglobin in Greeks.
In the Greek A gamma beta + type of hereditary persistence of fetal hemoglobin (HPFH), adult heterozygotes produce about 20% fetal hemoglobin (HbF), which is predominantly of the A gamma chain variety. The affected beta-globin gene cluster produces near normal amounts of beta-like globin, but in a A gamma to beta ratio of 20:80 instead of 0.5:99.5. Gelinas et al and Collins et al have shown a G to A change 117 nucleotides 5' to the A gamma gene in two Greeks with A gamma beta + HPFH. To demonstrate that this change is not a neutral polymorphism, we carried out hybridization with oligonucleotide probes (19mers) specific for the normal and the mutant sequences. While normal probe identified the A gamma fragment in genomic DNA of all subjects studied, mutant probe was positive only in Greeks with A gamma beta + HPFH. In sum, 108 beta-globin gene clusters of individuals without HPFH were negative when tested with mutant probe, but all 11 affected individuals of six families with Greek A gamma beta + HPFH (two previously sequenced and four new families) were positive with mutant probe. These data support the conclusion that the -117 mutation is causative of A gamma beta + HPFH in Greeks.
Waber
P G
PG
Bender
M A
MA
Gelinas
R E
RE
Kattamis
C
C
Karaklis
A
A
Sofroniadou
K
K
Stamatoyannopoulos
G
G
Collins
F S
FS
Forget
B G
BG
Kazazian
H H
HH
D005319:Fetal Hemoglobin / Q000235:genetics*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006115:Greece / Q000208:ethnology; D006801:Humans; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides; D010641:Phenotype
D009838:Oligodeoxyribonucleotides; D005914:Globins; D005319:Fetal Hemoglobin