Molecular basis for alpha-thalassemia associated with the structural mutant hemoglobin Suan-Dok (alpha 2 109leu----arg) [published erratum appears in Blood 1991 Mar 15;77(6):1404]

Autor:	Stephen A. Liebhaber, Ingrid Weiss, Annette Pressley, Mary B. Coleman, Junius G. Adams, T Sanguansermsri, Martin H. Steinberg, F E Cash
Rok vydání:	1990
Předmět:	Genetics Thalassemia Immunology Mutant Cell Biology Hematology Biology medicine.disease Biochemistry Hemoglobinopathy hemic and lymphatic diseases Mutation (genetic algorithm) medicine Missense mutation Hemoglobin Globin Gene
Zdroj:	Blood. 76:2630-2636
ISSN:	1528-0020 0006-4971
DOI:	10.1182/blood.v76.12.2630.2630
Popis:	Hemoglobin (Hb) Suan-Dok (alpha 109Arg) is a rare alpha-globin structural mutation that is linked to an alpha-thalassemia (alpha-thal) determinant. When inherited in trans to an alpha-thal-1 mutation (-), it results in Hb H disease associated with low levels (9%) of the Suan- Dok Hb. The nature of the thalassemic defect associated with the alpha SD mutation has been investigated by structural and functional studies. Sequence analysis of the cloned Suan-Dok allele showed a missense mutation (T----G) at codon 109 in an otherwise normal alpha 2-globin gene. When the alpha 2SD-globin gene was introduced into mouse erythroleukemia cells, the steady state alpha-globin messenger RNA (mRNA) level was equivalent to the alpha A-globin gene control. Although in vitro translation of a synthetic alpha 2SD-globin mRNA generated levels of alpha globin equivalent to alpha 2A-globin mRNA at early time points, the ratio of alpha SD to alpha A globin decreased markedly at later time points. These data suggest that the thalassemic defect associated with the Suan-Dok mutation results from a significant instability of the alpha SD globin.
Databáze:	OpenAIRE
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