Premium
γ‐mRNA and Hb F levels in β ‐thalassaemia
Author(s) -
Efremov D. G.,
Dimovski A. J.,
Sukarova E.,
Schiliro G.,
Zisovski N.,
Efremov G. D.,
Burrone O. R.,
Huisman T. H. J.
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb05024.x
Subject(s) - microbiology and biotechnology , heterozygote advantage , biology , messenger rna , globin , beta (programming language) , hemoglobinopathy , gene , genetics , compound heterozygosity , mutation , gene expression , genotype , hemolytic anemia , immunology , computer science , programming language
Summary. The Hb F levles in β ‐thalassaemia can be affected by factors both linked and unlinked to the β ‐globin gene cluster. We have recently analysed a group of patients with a homozygosity for the IVS‐1–6 (T → C) mutation, showing a wide variation in Hb F levels (2–47%) which could not be accounted for by any sequence variation within regulatory elements of the β ‐globin gene cluster. In order to further investigate factors underlying this phenotypic difference we have developed a competitive reverse trascription/polymerase chain reaction procedure and used this method to determine the relative amounts of γ‐and β ‐mRNAs in 10 patients with the IVS‐1–6 homozygosity and 15 heterozygous parents, two IVS‐I‐6 δβ‐thalassaemia compound heterozygotes, five homozygotes for the β d́; IVS‐I‐110 (G → A) mutation, and in two with a homozygosity for the β† codon 39 (C → T) mutation. Three heterozygotes were also included. The percentages of γ/(γ+β) mRNA were 10–73% in the IVS‐I‐6 homozygotes and <2% to 10% in their heterozygous parents. A direct relationship existed between the level of mRNA and the % Hb F. However, the relative γ‐mRNA levels in the IVS‐I‐6 homozygotes were higher than their Hb F levels, indicating a possible competition between the γ and β transcripts for translational factors with a less effcient initiation of protein synthesis on the γ‐mRNA or a preferential survival of cells with mainly β ‐globi gene expression at the post‐reticulocye stage. The γ‐mRNA levels in the two IVS‐I‐6/δβ‐thalassaemia compound heterozygotes were 71% and 62%, similar to their Hb F levels (63% and 59%), and averaged 82% (range 65–91%) in the five IVS‐I‐110 homozygotes and 97.5% in the two codon 39 homozygotes. The correlation between these values and the % Hb F could not be evaluated because of the transfusion regimens; however, the levels, of γ‐mRNA were as expected for patients with these β ‐thalassaemia alleles.