An initiation codon mutation (AUG----GUG) of the human alpha 1-globin gene. Structural characterization and evidence for a mild thalassemic phenotype.
alpha-globin is encoded by two adjacent genes, alpha 1 and alpha 2. Recent evidence suggests that these genes are not equally expressed and that the alpha 2-globin gene encodes the majority of alpha-globin. This finding would predict that a thalassemic mutation of the alpha 2-globin gene would result in a more severe loss of alpha-chain synthesis than a similar mutation in the alpha 1-globin gene. In a previous study we described a nondeletion alpha-thalassemia defect in the alpha 2-globin gene resulting from an AUG----ACG initiation codon mutation. In the present study we describe a different initiation codon mutation, AUG----GUG, present in the alpha 1-globin gene. The alpha 1- and alpha 2-globin gene initiation codon mutations result in similarly lowered levels of encoded mRNA. Despite the similarity of these two mutations, the alpha 2 mutant results in a more severe loss of alpha-globin synthesis and a more severe clinical alpha-thalassemia phenotype than the corresponding alpha 1-globin gene mutation. This difference reflects the dominant role of alpha 2-globin gene in overall alpha-globin synthesis.
Moi
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Ospedale Regionale per le Microcitemie USL21, Cagliari, Italy.
Cash
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FE
Liebhaber
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SA
Cao
A
A
Pirastu
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M
D001483:Base Sequence; D002648:Child; D003062:Codon; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012156:Reticulocytes / Q000378:metabolism; D013789:Thalassemia / Q000235:genetics*
D003062:Codon; D012333:RNA, Messenger; D005914:Globins