An IVS1-116 (A→G) acceptor splice site mutation in the α2 globin gene causing α+ thalassaemia in two Dutch families
| العنوان: | An IVS1-116 (A→G) acceptor splice site mutation in the α2 globin gene causing α+ thalassaemia in two Dutch families |
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| المؤلفون: | Monique Losekoot, Pierre W. Wijermans, H. L. Haak, C. L. Harteveld, Peter Van Delft, Luigi F. Bernini, D. Batelaan, Piero C. Giordano, J. G. A. M. Heister |
| المصدر: | British Journal of Haematology. 95:461-466 |
| بيانات النشر: | Wiley, 1996. |
| سنة النشر: | 1996 |
| مصطلحات موضوعية: | Genetics, Splice site mutation, Sequence Analysis, RNA, Sequence analysis, RNA Splicing, Nonsense mutation, Intron, DNA, Sequence Analysis, DNA, Hematology, Biology, Polymerase Chain Reaction, Molecular biology, Stop codon, Globins, Pedigree, Blotting, Southern, alpha-Thalassemia, Mutation, Consensus sequence, Humans, RNA, splice, Globin |
| الوصف: | We report the characterization of an alpha +(-)thalassaemia determinant due to a transition A-->G of the acceptor splice consensus site sequence (IVS1-116) of the first intron of the alpha 2-globin gene. The mutation, found in two apparently unrelated Dutch Caucasian families, was detected by DGGE analysis followed by direct sequencing. Haplotype analysis suggests a common origin of the mutation in both families. The disruption of the acceptor splice site consensus sequence interferes with the correct splicing and leads to the retention of the first intron in the abnormally spliced mRNA. The alpha +(-)thalassaemia phenotype observed in the carriers is caused by the absence of functional mRNA which cannot be replaced by the abnormally spliced mRNA. The low amounts of abnormal mRNA found in reticulocytes is, most probably, due to the post-transcriptional instability which follows the presence of a termination codon in the retained intronic sequence. This situation is often associated with a decreased mRNA stability as observed for several nonsense mutations of the beta-globin gene. |
| تدمد: | 0007-1048 |
| DOI: | 10.1046/j.1365-2141.1996.d01-1926.x |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::747a063bb1bf2bd3dd1cc1d31cd4a106 https://doi.org/10.1046/j.1365-2141.1996.d01-1926.x |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....747a063bb1bf2bd3dd1cc1d31cd4a106 |
| قاعدة البيانات: | OpenAIRE |
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