A New Hemoglobin Variant in Hungary: Hb Savaria-α49 (CE7) Ser+Arg

Szelényi, J.; Horányi, Margit; Földi, J.; Hudacsek, J.; Istvan, L; Hollán, Susan R.

doi:10.3109/03630268009042371

Cited by 25 publications

(1 citation statement)

References 11 publications

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“…However, other studies already described natural mutants occurring at these positions in human, with different amino acids (Szelényi et al 1980; Turbpaiboon et al 2002; Chang et al 2002; Akar et al 2003; Williams et al 2007). …”

Section: Discussionmentioning

confidence: 99%

Genomic Organization and Differential Signature of Positive Selection in the Alpha and Beta Globin Gene Clusters in Two Cetacean Species

Nery¹,

Opazo²

2013

Genome Biology and Evolution

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The hemoglobin of jawed vertebrates is a heterotetramer protein that contains two α- and two β-chains, which are encoded by members of α- and β-globin gene families. Given the hemoglobin role in mediating an adaptive response to chronic hypoxia, it is likely that this molecule may have experienced a selective pressure during the evolution of cetaceans, which have to deal with hypoxia tolerance during prolonged diving. This selective pressure could have generated a complex history of gene turnover in these clusters and/or changes in protein structure themselves. Accordingly, we aimed to characterize the genomic organization of α- and β-globin gene clusters in two cetacean species and to detect a possible role of positive selection on them using a phylogenetic framework. Maximum likelihood and Bayesian phylogeny reconstructions revealed that both cetacean species had retained a similar complement of putatively functional genes. For the α-globin gene cluster, the killer whale presents a complement of genes composed of HBZ, HBK, and two functional copies of HBA and HBQ genes, whereas the dolphin possesses HBZ, HBK, HBA and HBQ genes, and one HBA pseudogene. For the β-globin gene cluster, both species retained a complement of four genes, two early expressed genes—HBE and HBH—and two adult expressed genes—HBD and HBB. Our natural selection analysis detected two positively selected sites in the HBB gene (56 and 62) and four in HBA (15, 21, 49, 120). Interestingly, only the genes that are expressed during the adulthood showed the signature of positive selection.

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Section: Discussionmentioning

confidence: 99%

Genomic Organization and Differential Signature of Positive Selection in the Alpha and Beta Globin Gene Clusters in Two Cetacean Species

Nery¹,

Opazo²

2013

Genome Biology and Evolution

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HbS-Savaria: The Anti-polymerization Effect of a Single Mutation in Human α-chains

et al. 2007

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Recombinant alpha-Savaria globin (alpha(S49R)) was assembled with beta(S) chains by the alloplex intermediate pathway to generate tetrameric rHbS-Sarvaria (alpha (2) (S49R) beta (2) (E6V) ) that exhibited normal O(2) affinity and co-operatively at pH 7.4. Allosteric effectors, 2,3-DPG, L35, and NaCl increased O(2) affinity by 15%. Bohr effects were similar for rHbS-Savaria and HbS (0.38 +/- 0.025 vs. 0.46 +/- 0.03, respectively). The C(SAT) of HbS increased from 16.7 +/- 0.8 to 27.0 +/- 1.0 g/dL. Co-polymerization demonstrated inhibition predominantly by the Cis-dimer. Molecular modeling indicated that the positive charge at alpha-49 generated a strong anion-binding site and reduced flexibility of the CD-region by restricting movement in the E and F helices. The molecular distance between Arg-49 and Asn-78 in the neighboring double strand decreased, and electrostatic repulsion between the inter-double strands increased, resulting in inhibition of polymerization. The Savaria mutation may be useful for the design of super-inhibitory alpha-chains and gene therapy of sickle cell anemia.

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Hb Savaria [α49(CE7)Ser→Arg;HBA2: c.150C > A]: A New Case and Complete Description

et al. 2016

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Hb Savaria [α49(CE7)Ser→Arg; HBA2: c.150C > A] is a rare hemoglobin (Hb) variant, initially described in Eastern Europe but present worldwide. It belongs to that class of variants which can be confused with Hb S [β6(A3)Glu→Val; HBB: c.20A > T] by automated protein analysis and thus needs special tests for proper identification. Because it could arise from different nucleotide substitutions and according to the rules of the Human Genome Variation Society (HGVS) nomenclature, three 'Hb Savaria' variants are possible. In the case reported here it resulted from the HBA2: c.148A > C change.

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A New Hemoglobin Variant in Hungary: Hb Savaria-α49 (CE7) Ser+Arg

Abstract: A hemoglobin variant of slow electrophoretic mobility has been demonstrated in a Hungarian female patient. The abnormal component amounted to about 30% and proved to be a new hemoglobin variant, alpha 49 (CE7) Ser replaced by Arg, which has been named Hb Savaria.

Cited by 25 publications

References 11 publications

Genomic Organization and Differential Signature of Positive Selection in the Alpha and Beta Globin Gene Clusters in Two Cetacean Species

Genomic Organization and Differential Signature of Positive Selection in the Alpha and Beta Globin Gene Clusters in Two Cetacean Species

HbS-Savaria: The Anti-polymerization Effect of a Single Mutation in Human α-chains

Hb Savaria [α49(CE7)Ser→Arg;HBA2: c.150C > A]: A New Case and Complete Description

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