Delta zero-thalassemia in cis of beta Knossos-globin gene. Normal structure transient expression of the delta-globin gene.
We have previously described the first homozygous cases of Hb Knossos in an Algerian family. The Hb A2 was completely absent, ascertaining the presence of a delta zero-thalassemia determinant in cis of the beta Knossos S gene. Here, we investigate the affected delta-globin gene. The complete DNA sequence of the gene and its 5' and 3' flanking regions was determined. Only two nucleotide changes were recorded: a C----T substitution at -199 and an AT insertion at -448 upstream from the cap site. To examine the involvement of these changes in gene function, the delta-gene was subcloned in an expression vector and introduced into COS cells. Analysis of RNA derived from these cells, using an S1 protection assay and dot-blot hybridization, revealed qualitatively and quantitatively normal transcription. The loss of delta-globin gene activity in vivo may be due to the alteration of a tissue-specific control.
Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 106, Villeurbanne, France.
R
R
Ouazana
D
D
Bozon
F
F
Baklouti
C
C
Gonnet
J
J
Delaunay
J
J
Godet
D004247:DNA / Q000032:analysis; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D013789:Thalassemia / Q000235:genetics*; D014158:Transcription, Genetic
D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; C036232:hemoglobin Knossos; D005914:Globins; D004247:DNA