Hemoglobin Casper G8 β106 Leu→ Pro: Further Evidence that Hemoglobin Mutations are Not Random

  • R. T. Jones
  • R. D. Koler
  • M. Duerst
  • Z. Stocklen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 28)


During the past 10 years unstable hemoglobins have been detected and characterized with increasing frequency (Carrel 1 and Lehmann, 1969; Huehns, 1970). This accelerated recognition has resulted in part from greater awareness that hemolytic anemias may result from unstable hemoglobins. In addition, the development and application of relatively simple laboratory tests that will detect chemically unstable hemoglobins such as the Heinz body generation test (Beutler et al, 1955) and the heat denaturation procedure of Grimes and Meisler (1962) have provided rapid methods for confirming the diagnosis. A review of more than 30 different unstable hemoglobins reported to date reveals correlations between clinical severity and chemical alterations (Koler et al, 1972). It would appear that clinical awareness and ease of laboratory diagnos is have reached a point where most unstable hemoglobins which cause severe postnatal hemolytic disease may be detected. With high like lihood of ascertainment and with information about structural changes, insight into mutational events and their impact on protein structure and function can be gained.


Hemolytic Anemia Hemoglobin Variant Abnormal Hemoglobin Prolyl Residue Chain Mutant 
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  1. Allen, D. W., Schroeder, W. A. and Balog, J. (1958). Observations on the chromatographic heterogeneity of normal adult and fetal hemoglobin: A study of the effects of crystallization and chromatography on the heterogeneity and isoleucine content. J. Am. Chem. Soc. 80: 1628.CrossRefGoogle Scholar
  2. Beutler, E., Dern, R. J. and Alving, A. S. (1955). The hemolytic effect of primaquine. VI. An in vitro test for sensitivity of erythrocytes to primaquine. J. Lab. amp; Clin. Med. 49: 84.Google Scholar
  3. Carrell, R. W. and Lehmann, H. (1969). The unstable haemoglobin haemolytic anaemias. Seminars Hemato 6:116,Google Scholar
  4. Clegg, J. B., Naughton, M. A, and Weatherall, D. J. (1966). Abnormal human haemoglobins: Separation and characterization of the α- and β-chains by chromatography, and the determination of two new variants, Hb Chesapeake and Hb J (Bangkok). J. Hoi. Biol. 19: 91.CrossRefGoogle Scholar
  5. Clegg, J. B., Weatherall, D. J. and Milner, P. F. (1971). Haemoglobin Constant Spring-a chain termination mutant? Nature 234: 337.PubMedCrossRefGoogle Scholar
  6. Dayhoff, M. O. (1969). Atlas of protein sequence and structure. 4:7 Nat. Biomed. Res. Fdn.Google Scholar
  7. Edwards, M. J. and Martin, R. J. (1966). Mixing technique for the oxygen-hemoglob1n equilibrium and the Bohr effect. J. Appl. Physiol. 21: 1898.PubMedGoogle Scholar
  8. Gray, W. R. (1967). Dansyl chloride procedure. In Methods in Enzymology. 11:139, Ed. C. H. W. Hirs., Academic Press, New York.Google Scholar
  9. Grimes, A. J. and Meisler, A. (1962), Possible cause of Heinz bodies in congenital Heinz-body anaemia. Nature 194: 190.CrossRefGoogle Scholar
  10. Hollán, S. R., Szelnyi, J. G., Miltényl, M., Charlesworth, D., Lorkin, P. A. and Lehmann, H. (1970). Unstable haemoglobin disease caused by Hb Santa Ana-β88 ( F4) Leu→Pro. Haematologia 4: 141.PubMedGoogle Scholar
  11. Huehns, E. R. (1970). Diseases due to abnormalities of hemoglobin structure. Ann. Rev. Med. 21: 157.PubMedCrossRefGoogle Scholar
  12. Huisman, T. H. J. and Dozy, A. M. (1965). Studies on the heterogeneity of hemoglobin; IX. The use of tris (hydroxymethyl) aminomethane-HC1 buffers in the anion exchange chromatography of hemoglobins. J. Chromatog. 19: 160.CrossRefGoogle Scholar
  13. Huisman, T. H. J. (1963). Normal and abnormal hemoglobins. Adv. Clin. Chem. 6: 231.PubMedCrossRefGoogle Scholar
  14. Jones, R. T. (1964). Structural studies of aminoethylated hemoglobins by automatic peptide chromatography. Cold Spring Harbor Sympos. Quant. Biol. 29: 297.CrossRefGoogle Scholar
  15. Kleihauer, E. F., Reynolds, C. A., Dozy, A. M., Wilson, J. B., Moores, R. R., Berenson, M. P., Wright, C. S. and Hulsman, T. H. J. (1968). Hemoglobin Bibba or α2136Proß2, an unstable a chain abnormal hemoglobin. Biochim. Biophys. Acta 154: 220.PubMedGoogle Scholar
  16. Koler, R. D., Jones, R. T. and Bigley, R. D. (1972) In preparation.Google Scholar
  17. Konigsberg, W. (1967). Subtractive Edman Degradation, In Methods in Enzymology. 11:461, ed. C. H. W. Hirs., Academic Press, New York.Google Scholar
  18. Lehmann, H. and Huntsman, R. D. (1972). The hemoglobinopathies. In Stanbury, J. B., Wyngaarden, J. B. and Frederickson, D. S. (Eds). The Metabolic Basis of Inherited Disease. 3rd ed. p. 1398, McGraw Hill, New York.Google Scholar
  19. Lehmann, H. and Carrel 1, R. W. (1969). Variations in structure of human haemoglobin. Brit. Med. Bull. 25: 14PubMedGoogle Scholar
  20. Opfell, R. W., Lorkin, P. A. and Lehmann, H. (1968). Hereditary non-spherocytic haemolytic anaemia with post-splenectomy inclusion bodies and pigmenturia caused by an unstable haemoglobin Santa- Ana-ß88 (F4) leucine→prol ine. J. Med. Geneto 5: 292.CrossRefGoogle Scholar
  21. Perutz, M. F. (1970). Stereochemistry of cooperative effects in haemoglobin. Nature 228: 726.PubMedCrossRefGoogle Scholar
  22. Perutz, M. F., Muirhead, H., Cox, J. M. and Goaman, L. C. G. (1968) Three-dimensional Fourier synthesis of horse oxyhaemoglobin at 2.8 Å resolution: The atomic model. Nature 219: 131.PubMedCrossRefGoogle Scholar
  23. Rosemeyer, M. A. and Huehns, E. R. (1967). On the mechanism of the dissociation of haemoglobin. J. Mol. Biol. 25: 253.PubMedCrossRefGoogle Scholar
  24. Sanger, F. (1971). Nucleotide sequences in bacteriophage ribonucleic 3cid. ( The Eight Hopkins Memorial Lecture ). Biochem. J. 124: 833Google Scholar
  25. Sansone, G. and Pik, C. (1965). Familial haemolytic anaemia with erythrocyte inclusion bodies, bi1ifuscinuria and abnormal haemoglobin (Haemoglobin Galliera Genova). Brit J. Haematol. 11: 511.CrossRefGoogle Scholar
  26. Schneider, R. G., Ueda, S., Alperin, J., Brimhall, B. and Jones, R. T. (1969). Hemoglobin Sabine Beta 91 (F7) Leu→Pro. New Eng. J. Med. 280: 739.PubMedCrossRefGoogle Scholar
  27. White, H. B. Ill, Laux, B. E. and Dennis, D. (1972). Messenger RNA structure: Compatibility of hairpin loops with protein sequence. Science 175: 1264.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1972

Authors and Affiliations

  • R. T. Jones
    • 1
  • R. D. Koler
    • 2
  • M. Duerst
    • 1
  • Z. Stocklen
    • 2
  1. 1.Department of BiochemistryUniversity of Oregon Medical SchoolPortlandUSA
  2. 2.Div. of Medical GeneticsUniversity of Oregon Medical SchoolPortlandUSA

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