Nondeletional type of hereditary persistence of fetal haemoglobin: molecular characterization of three unrelated Thai HPFH.
The beta-globin gene clusters of three unrelated Thai families with a nondeletional type of hereditary persistence of fetal haemoglobin (HPFH) were studied using polymerase chain reaction-related techniques. All appeared to have normal nucleotide sequences from the Cap site to position -400 of both the G gamma- and A gamma-globin genes. Two individuals suspected of having a beta-thalassaemia gene linked to the high HbF condition also had a normal beta-globin gene sequence, spanning from position -108 from the Cap site to the polyadenylation site. Deletion of four nucleotides, AGCA, at positions -225 to -222 of one A gamma-globin allele was detected in one subject and was confirmed by dot-blot hybridization. Restriction fragment length polymorphisms in the beta-globin gene cluster showed that the 5' haplotype (-+-++) and the presence (+) of an Xmm 1 polymorphic site at -158 of the G gamma-globin gene are associated with the high F phenotype in these families. Direct sequencing of the 5' hypersensitive-2 (5' HS-2) site of the locus control region (LCR) showed that this Xmn 1 (+) site is also linked to a specific rearrangement of TA repeats (TA)9CACATATACG(TA)10, in HS-2 segment.
Winichagoon
P
P
Department of Medicine, Faculty of Medicine, Siriraj Hospital, Thailand.
Fucharoen
S
S
Wilairat
P
P
Chihara
K
K
Fukumaki
Y
Y
D000328:Adult; D000368:Aged; D001483:Base Sequence; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006453:Hemoglobinopathies / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013785:Thailand; D013789:Thalassemia / Q000235:genetics*
D005914:Globins; D005319:Fetal Hemoglobin