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Hb Osler [beta 145(HC2)Tyr-->Asp] results from posttranslational modification
A C Kattamis1, K M Kelly, K Ohene-Frempong
1Division of Hematology, Children's Hospital of Philadelphia, PA, USA.
Hemoglobin
|March 1, 1997
Summary
A novel hemoglobin variant, Hb Osler, was identified in an African American family with erythrocytosis. This high oxygen affinity hemoglobin results from a beta-globin gene mutation and posttranslational modification.
Area of Science:
- Molecular Biology
- Hematology
- Genetics
Background:
- Erythrocytosis can be caused by inherited hemoglobin variants affecting oxygen transport.
- Hemoglobinopathies represent a significant area of research in inherited blood disorders.
Purpose of the Study:
- To investigate the molecular basis of erythrocytosis in an African American family.
- To characterize a novel abnormal hemoglobin variant.
Main Methods:
- Electrophoresis to identify abnormal hemoglobin.
- Oxygen dissociation curve analysis.
- DNA sequencing of the beta-globin gene.
- Amino acid sequence analysis of globin chains.
Main Results:
- Identified an abnormal hemoglobin variant with electrophoretic properties similar to Hb J.
- Oxygen dissociation curve showed high oxygen affinity (left-shifted and hyperbolic).
- DNA analysis revealed a T to A mutation at codon 145 of the beta-globin gene, leading to a tyrosine to asparagine substitution.
- Amino acid analysis confirmed the presence of asparagine and aspartic acid at the C-terminus, indicating posttranslational deamidation.
Conclusions:
- The identified mutation and subsequent posttranslational modification result in Hb Osler, a high oxygen affinity hemoglobin variant.
- Posttranslational modification of amino acids plays a role in the pathophysiology of hemoglobinopathies.