Duplication of the haemoglobin α gene

S. Hollán, D. H. Lanh, J. Foldi, M. Horányi, J. Szelényi

Research output: Contribution to journalArticle

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Abstract

Gene duplication is one of the basic processes underlying evolutionary changes. The γ chains of human foetal haemoglobin is coded by multiple structural genes. The δ chains of Hb A2 can be regarded as a duplication of the β locus. The authors have presented the first evidence for the presence of two major α chain loci in man. The α gene appears to have duplicated recently, since apart of the single point mutations characterizing Hb J Buda and Hb G Pest, the two α gene products seem to be identical. Sensitive immunochemical measurement techniques may reveal structural differences which might escape detection by chemical methods based on differences in charge and/or chromatographic behaviour. Anti α chain sera recognizing the single amino acid substitution in αJ Buda could be raised in rabbits. The anti α chain sera were found to be more powerful tools for detecting differences in the primary structure of the chain than the immune sera raised against the whole tetramer. None of the immune sera could reliably differentiate Hb G Pest from Hb A1. The relative strength of complement fixation of the α chains from haemoglobin A1 F and A2 was compared by hybridizing these human haemoglobins with canine haemoglobin and measuring the quantitative complement fixation of the different hybrids with anti Hb A1 and anti α(A1) rabbit immune sera. No antigenic difference among the α chains from haemoglobins A1, A2 and F could be detected by this method either with anti A1 or with anti α(A1) sera. These results do not exclude the possibility of conformational differences between the α chains in native Hb A and Hb F. The antigenic activity of the α chains of Hb A from normal subjects (α(A1)) and of the α chains of Hb A from a double heterozygote for αJ Buda and αG Pest (α(A1)') were compared by the complement fixation technique. Definite differences could be detected in the relative strength of complement fixation by α(A1) and α(A1)' with anti α(A1)' serum. Final decision as to whether α chain duplication is a universal phenomenon or whether it is restricted to only a part of mankind cannot be drawn until the presence of a silent α thalassaemia gene is not excluded in some debated cases by reliable chemical methods. Measurement of α globin genes in Hb H disease with cDNA enriched in α globin sequences provided direct evidence that a non thalassaemic subject has to have at least four α globin genes per diploid cell. (Journal received March 1977)

Original languageEnglish
Pages (from-to)245-254
Number of pages10
JournalActa Medica Academiae Scientiarum Hungaricae
Volume32
Issue number3-4
Publication statusPublished - 1975

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Gene Duplication
Hemoglobins
Fetal Hemoglobin
Globins
Glycosylated Hemoglobin A
Hemoglobin A2
Genes
Immune Sera
Serum
Rabbits
Thalassemia
Amino Acid Substitution
Heterozygote
Diploidy
Point Mutation
Canidae
Complementary DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Duplication of the haemoglobin α gene. / Hollán, S.; Lanh, D. H.; Foldi, J.; Horányi, M.; Szelényi, J.

In: Acta Medica Academiae Scientiarum Hungaricae, Vol. 32, No. 3-4, 1975, p. 245-254.

Research output: Contribution to journalArticle

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abstract = "Gene duplication is one of the basic processes underlying evolutionary changes. The γ chains of human foetal haemoglobin is coded by multiple structural genes. The δ chains of Hb A2 can be regarded as a duplication of the β locus. The authors have presented the first evidence for the presence of two major α chain loci in man. The α gene appears to have duplicated recently, since apart of the single point mutations characterizing Hb J Buda and Hb G Pest, the two α gene products seem to be identical. Sensitive immunochemical measurement techniques may reveal structural differences which might escape detection by chemical methods based on differences in charge and/or chromatographic behaviour. Anti α chain sera recognizing the single amino acid substitution in αJ Buda could be raised in rabbits. The anti α chain sera were found to be more powerful tools for detecting differences in the primary structure of the chain than the immune sera raised against the whole tetramer. None of the immune sera could reliably differentiate Hb G Pest from Hb A1. The relative strength of complement fixation of the α chains from haemoglobin A1 F and A2 was compared by hybridizing these human haemoglobins with canine haemoglobin and measuring the quantitative complement fixation of the different hybrids with anti Hb A1 and anti α(A1) rabbit immune sera. No antigenic difference among the α chains from haemoglobins A1, A2 and F could be detected by this method either with anti A1 or with anti α(A1) sera. These results do not exclude the possibility of conformational differences between the α chains in native Hb A and Hb F. The antigenic activity of the α chains of Hb A from normal subjects (α(A1)) and of the α chains of Hb A from a double heterozygote for αJ Buda and αG Pest (α(A1)') were compared by the complement fixation technique. Definite differences could be detected in the relative strength of complement fixation by α(A1) and α(A1)' with anti α(A1)' serum. Final decision as to whether α chain duplication is a universal phenomenon or whether it is restricted to only a part of mankind cannot be drawn until the presence of a silent α thalassaemia gene is not excluded in some debated cases by reliable chemical methods. Measurement of α globin genes in Hb H disease with cDNA enriched in α globin sequences provided direct evidence that a non thalassaemic subject has to have at least four α globin genes per diploid cell. (Journal received March 1977)",
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N2 - Gene duplication is one of the basic processes underlying evolutionary changes. The γ chains of human foetal haemoglobin is coded by multiple structural genes. The δ chains of Hb A2 can be regarded as a duplication of the β locus. The authors have presented the first evidence for the presence of two major α chain loci in man. The α gene appears to have duplicated recently, since apart of the single point mutations characterizing Hb J Buda and Hb G Pest, the two α gene products seem to be identical. Sensitive immunochemical measurement techniques may reveal structural differences which might escape detection by chemical methods based on differences in charge and/or chromatographic behaviour. Anti α chain sera recognizing the single amino acid substitution in αJ Buda could be raised in rabbits. The anti α chain sera were found to be more powerful tools for detecting differences in the primary structure of the chain than the immune sera raised against the whole tetramer. None of the immune sera could reliably differentiate Hb G Pest from Hb A1. The relative strength of complement fixation of the α chains from haemoglobin A1 F and A2 was compared by hybridizing these human haemoglobins with canine haemoglobin and measuring the quantitative complement fixation of the different hybrids with anti Hb A1 and anti α(A1) rabbit immune sera. No antigenic difference among the α chains from haemoglobins A1, A2 and F could be detected by this method either with anti A1 or with anti α(A1) sera. These results do not exclude the possibility of conformational differences between the α chains in native Hb A and Hb F. The antigenic activity of the α chains of Hb A from normal subjects (α(A1)) and of the α chains of Hb A from a double heterozygote for αJ Buda and αG Pest (α(A1)') were compared by the complement fixation technique. Definite differences could be detected in the relative strength of complement fixation by α(A1) and α(A1)' with anti α(A1)' serum. Final decision as to whether α chain duplication is a universal phenomenon or whether it is restricted to only a part of mankind cannot be drawn until the presence of a silent α thalassaemia gene is not excluded in some debated cases by reliable chemical methods. Measurement of α globin genes in Hb H disease with cDNA enriched in α globin sequences provided direct evidence that a non thalassaemic subject has to have at least four α globin genes per diploid cell. (Journal received March 1977)

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