Normal delta-globin gene sequences in Sardinian nondeletional delta beta-thalassemia.
In order to clarify the reasons for the reduced Hb A2 levels in Sardinian delta beta-thalassemia, we characterized, both by cloning and sequence analysis and by direct sequencing of amplified DNA, the delta-globin gene from an individual of Sardinian descent who is a compound heterozygote for the beta zero-thalassemia codon 39 (C-->T) nonsense mutation and the Sardinian delta beta-thalassemia [codon 39(C-->T)/-196(C-->T)A gamma]. The analysis of the delta-globin gene from the delta beta-thalassemia chromosome revealed an entirely normal sequence. The defective function of the delta-globin gene in this determinant is thus likely related to a suppressive effect of the in cis nondeletional high persistence of fetal hemoglobin mutation of the A gamma gene, probably resulting from an increased capability of the relative promoter to interact with the locus control region.
Loudianos
G
G
Istituto di Clinica e Biologia, Eta Evolutiva Universita degli Studi di Cagliari, Italia.
Moi
P
P
Lavinha
J
J
Galanello
R
R
Cao
A
A
Pirastu
M
M
D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D017353:Gene Deletion; D005914:Globins / Q000235:genetics*; D006403:Hematologic Tests; D006579:Heterozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D012016:Reference Values; D013489:Suppression, Genetic / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics*
D005914:Globins; D004247:DNA