title: The differences in quantities of alpha 2- and alpha 1-globin gene variants in heterozygotes.
abstract: We have identified through sequencing of amplified DNA the mutations in the alpha 2- and alpha 1-globin genes in 63 individuals with a heterozygosity for an alpha chain abnormal haemoglobin (Hb). Moreover, we developed a reverse transcription/polymerase chain reaction (RT/PCR) based procedure for the determination of the alpha 2- and alpha 1-mRNA ratio in normal individuals. The numbers of alpha 2 and alpha 1 variants were nearly the same. The average percentage of the abnormal Hb in heterozygotes with alpha 2 mutations (23.5%) was slightly higher than that in heterozygotes with alpha 1 mutations (19.7%) (stable Hbs only). These percentages correspond to a ratio of alpha 2 to alpha 1 of 1.19 to 1 at the protein level. Variations in the number of active alpha-globin genes and in the stability of the variants (greatly) affected the percentages of the abnormal protein. The average ratio between the alpha 2- and alpha 1-mRNAs in 12 normal individuals was 2.6-2.75 to 1, about as expected from published data, and 2.0 to 1 for two persons with an alpha-thalassaemia-2 (alpha-thal-2) (-3.7 kb) heterozygosity. The high relative mRNA (alpha 2) level which is about twice the relative level of the alpha 2 protein suggests a less efficient translation of the alpha 2-mRNA.
authors: Laboratory of Protein Chemistry, Medical College of Georgia, Augusta 30912-2100.
authors: T P
authors: TP
authors: Molchanova
authors: D D
authors: DD
authors: Pobedimskaya
authors: T H
authors: TH
authors: Huisman
mesh_terms: D001483:Base Sequence; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; D005914:Globins