Abstract
The question of how genetic material controls phenotypic expression was posed 60 years ago by Hermann Muller (1922), but the ability to answer the question awaited the development of biochemical techniques capable of dissecting and comparing purified proteins (Moore et al., 1958; Edman and Sjöquist, 1956; Ingram, 1957). Human haptoglobin has served as an unexpected source of information relating the mechanisms involved in genetic rearrangements to the linear sequence of amino acids within a protein. After developing a potent technique, starch gel electrophoresis, which proved capable of resolving and identifying previously unknown inherited variations in many human plasma proteins, Oliver Smithies and co-workers (Smithies, 1959; Smithies et al., 1962a, 1962b) demonstrated that serum haptoglobin molecules from different individuals varied one from another in a heritable way. Haptoglobin has served as an impressive paradigm of how genetic rearrangements can construct a polymorphic system and how, in the evolutionary process, old proteins can obtain new functions by utilizing amino acid sequences which have been ever so slightly altered. Excellent reviews have been written about haptoglobin, which can be consulted for further detail (Javid, 1978; Putnam, 1975; Pintera, 1971; Sutton, 1970; Giblett, 1969; Kirk, 1968; Schultze and Heremans, 1966). This review will emphasize recent developments in analyzing the composition of the haptoglobin molecules and the evolutionary implications of these findings.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alfsen, A., Chiancone, E., Wyman, J., and Antonini, E., 1970, Studies on the reaction of haptoglobin with hemoglobin and hemoglobin chains. II. Kinetics of complex formation, Biochem. Biophys. Acta 200: 76–80.
Allison, A. C., 1959, Genetic control of human haptoglobin synthesis, Nature 183: 1312–1314.
Allison, A. C., and apRees, W., 1957, The binding of haemoglobin by plasma proteins (haptoglobins), Br. Med. J. 2: 1137–1143.
Allison, A. C., Blumberg, B. S., and apRees, W., 1958, Haptoglobin types in British, Spanish Basque and Nigerian African populations, Nature 181: 824–825.
Aly, F. W., Brinker, G., Cleve, H., Deicher, H., Hartman, F., and Nix, W., 1961, Die Bestimmung der Haptoglobingruppen mit Hilfe einfacher immunologischer Methoden. Klin. Wochenschr. 39: 610.
Arnone, A., and Williams, D. L., Jr., 1977, Crystallographic evidence for anion binding sites at the NH2-termini of the a subunits of deoxyhemoglobin, in: Les Colloques de L’Institute National de la Santé et de la Recherche Médicale: Interactions moléculaires de l’hémoglobine (D. Labre, C. Povart, and J. Rosa, eds), pp. 15–22, Inserm, Paris.
Aubert, J.-P., Biserte, G., and Loucheux-Lefebvre, M.-H., 1976, Carbohydrate-peptide linkage in glycoproteins, Arch. Biochem. Biophys. 175: 410–418.
Azevedo, E., Krieger, H., and Morton, N. E., 1969, Ahaptoglobinemia in Northeastern Brazil, Hum. Hered. 19: 603–612.
Baglia, F. A., and Fuller, G. M., 1981, Haptoglobin synthesis in cultured hepatoma cells: Modulating effects of steroids and prostaglandin E1, Submitted.
Baglia, F. A., Kwan, S.-W., and Fuller, G. M., 1981, Haptoglobin biosynthesis in rats: Immunological identification of polysomes synthesizing haptoglobin, quantitation of haptoglobin in the cytoplasm of liver cells, Submitted.
Barnett, D. R., Lee, T-H., and Bowman, B. H., 1970, Amino-acid sequence of the carboxyl terminal octapeptide of human haptoglobin β-chain, Nature 225: 938–939.
Barnett, D. R., Lee, T.-H., and Bowman, B. H., 1972, Amino acid sequence of the human haptoglobin β chain. I. Amino- and carboxyl terminal sequences, Biochemistry 11: 1189–1194.
Barnett, D. R., Kurosky, A., Fuller, G. M., Kim, H. H., Rasco, M. A., and Bowman, B. H., 1975, Structural characterization and genetic variation of haptoglobin, in: Protides of the Biological Fluids 22nd Colloquim (H. Peeters, ed.), pp. 589–595, Pergamon Press, New York.
Bayani-Sioson, P. S., Louch, J., Sutton, H. E., Neel, J. V., Horne, S. L., and Gershowitz, H., 1962, Quantitative studies on the haptoglobin of apparently adult male twins, Am. J. Hum. Genet. 14: 210–219.
Bearn, A. G., and Franklin, E. C., 1958, Some genetical implications of physical studies of human haptoglobins, Science 128: 596–597.
Bearn, A. G., and Franklin, E. C., 1959, Comparative studies of the physical characteristics of the heritable haptoglobin groups of human serum, J. Exp. Med. 109: 55–68.
Becker, W., Heimburger, N., Schwick, H. G., and Störiko, K., 1970, Immunological determination of biologically active plasma proteins, in: Methods in Clinical Chemistry (M. Roth, ed.), pp. 144–151, Karger, Basel, New York.
Benesch, R. E., and Benesch, R., 1974, The mechanism of interaction of red cell organic phosphates with hemoglobin, in: Advances in Protein Chemistry (C. B. Anfinsen, J. T. Edsall, and F. M. Richards, eds.), pp. 211–237, Academic Press, New York.
Benesch, R. E., Ikeda, S., and Benesch, R., 1976, Reaction of haptoglobin with hemoglobin covalently cross-linked between the αβ dimers, J. Biol. Chem. 251: 465–470.
Berggård, I., and Bearn, A. G., 1962, Excretion of haptoglobin in normal urine, Nature 195: 1311–1312.
Berggård, I., Cleve, H., and Bearn, A. G., 1964, The excretion of five plasma proteins previously unidentified in normal human urine, Clin. Chim. Acta 10: 1–11.
Bergstrand, C. G., Czar, B., and Tarukoski, P. H., 1961, Serum haptoglobin in infancy, Scand. J. Clin. Lab. Inv. 13: 576–582.
Bernini, L., Borri-Voltattorni, C., and Siniscalco, M., 1966, Studies on dissociation and reassociation of haptoglobins. Hybridization between Hp1 Hp1 and Hp2 Hp2, Atti Accad. Naz. Lincei Rend. Classe Sci. fis. mat. nat. 40: 279–289.
Bias, W. B., and Migeon, B. R., 1965, Haptoglobin: A locus on the D. chromosome, Am. J. Hum. Genet. 19: 393–398.
Bias, W. B., Amos, D. B., Ward, F. E., Yoder, O. C., Renwick, J. H., and McKusick, V. A., 1972, No linkage between HL-A and haptoglobin loci, Am. J. Hum. Genet. 24: 354–355.
Black, J. A., and Dixon, G. H., 1968, Amino-acid sequence of alpha chains of human haptoglobins, Nature 218: 736–741.
Black, J. A., and Dixon, G. H., 1970, Gene action in human haptoglobins IV. Amino acid sequence studies on the haptoglobin alpha chains, Can. J. Biochem. 48: 133–146.
Black, J. A., Chan, G. F. Q., Hew, C. L., and Dixon, G. H., 1970, Gene action in the human haptoglobins. III. Isolation of the α chains as single gene products. Isolation, molecular weight, and amino acid composition of α and β chains, Can. J. Biochem. 48: 123–132.
Bloom, G. E., Gerald, P. S., and Reisman, L. E., 1967, Ring D chromosome: A second case associated with anomalous haptoglobin inheritance, Science, 156: 1746–1748.
Blow, D. M., Birktoft, J. J., and Hartley, B. S., 1969, Role of a buried acid group in the mechanism of action chymotrypsin, Nature 221: 337–340.
Bodmer, W. F., Bodmer, J. G., Coukell, A., Cann, H., and vanWest, B., 1971, Some further data on the joint segregation of HL-A and haptoglobin, Ann. Hum. Genet. 35: 167–169.
Boyd, N. D., Smith, D. B., and Andrews, D., 1971, The reaction of hemoglobin with the complex formed from haptoglobin and hemoglobin α-subunits, Can. J. Biochem. 49: 891–893.
Braun, H. J., and Aly, F. W., 1969, Problems in the quantitative estimation of human serum haptoglobin by single radial immunodiffusion, Clin. Chim. Acta 26: 588–590.
Bridges, C. B., 1936, The bar “gene” duplication, Science 83: 210–211.
Brissaud, H. E., 1941, Étude Clinique de l’haptoglobine, Masson, Paris.
Buettner-Janusch, J., Buettner-Janusch, V., and Sale, J. B., 1964, Plasma proteins and haemoglobins of the African elephant and the hyrax, Nature 201: 510–511.
Burtin, P., Grabar, P., Boussier, G., and Jayle, M., 1954, Etude immunochimique de l’haptoglobine, Bull. Soc. Chim. Biol. 36: 1029–1035.
Butkowski, R. J., Elion, J., Downing, M. R., and Mann, K. G., 1977, Primary structure of human prethrombin α and α-thrombin, J. Biol. Chem. 252: 4942–4957.
Cheftel, R.-I., and Moretti, M. J., 1966, Biochimie—Sur le structure des haptoglobines humanies, C. R. Acad. Sci., Ser. D 262: 1982–1988.
Chiancone, E., Alfsen, A., Ioppolo, C., Vecchini, P., Agrò, A. F., Wyman, J., and Antonini, E., 1968, Studies on the reaction of haptoglobin with haemoglobin and haemoglobin chains, J. Mol. Biol. 34: 347–356.
Choi, Y.-M., and Shim, B.-S., 1967, Immunochemical characterization of haptoglobin P variants, Theses of Catholic Medical College, Seoul, Korea 13: 277–288.
Chow, V., Kurosky, A., and Murray, R. K., 1980, Biosynthesis in vitro of a putative precursor of haptoglobin, J. Cell. Biol. 87: 296a.
Cleve, H., and Deicher, H., 1965, Haptoglobin Marburg; Untersuchungen über eine seltene ubliche Haptoglobin-Variante mit zivei verschiedenen Phänotypen innerhalb einer Familie, Humangenetik 1: 537–550.
Cleve, H., and Herzog, P., 1969, Phenotype variations of haptoglobin Johnson types, Humangenetik 7: 218–224.
Cleve, H., Gordon, S., Bowman, B. H., Bearn, A. G., 1967, Comparison of tryptic peptides and amino acid composition of the beta polypeptide chains of the three common haptoglobin phenotypes, Am. J. Hum. Genet. 19: 713–721.
Cleve, H., Bowman, B. H., and Gordon, S., 1969, Biochemical characterization of the β-chain variant haptoglobin Marburg, Humangenetik 7: 337–343.
Cloarec, L., and Moretti, J., 1966, Combinaison de l’hémoglobine avec les divers polyméres constitutifs de l’haptoglobine, C. R. Acad. Sci. Paris 262: 2081.
Cloarec, L., Moretti, J., and Rafelson, M., 1963, Composition chimique de l’haptoglobine humaine, C. R. Acad. Sci. Paris 257: 983–985.
Cohen-Dix, P., Noble, R. W., and Reichlin, M., 1973, Comparative binding studies of the hemoglobin-haptoglobin and the hemoglobin-antihemoglobin reactions, Biochemistry 12: 3744–3751.
Connell, G. E., and Smithies, O., 1959, Human haptoglobins: Estimation and purification, Biochem. J. 72: 115–121.
Connell, G. E., Dixon, G. H., and Smithies, O., 1962, Subdivision of the three common haptoglobin types based on “hidden” differences, Nature 193: 505–506.
Connell, G. E., Smithies, O., and Dixon, G. H., 1966, Gene action in the human haptoglobins II. Isolation and physical characterization of alpha polypeptide chains, J. Mol. Biol. 21: 225–229.
Constans, J., and Viau, M., 1977, Polymorphisms of the haptoglobin peptide chains in Pyrenean populations, Am. J. Hum. Genet. 29: 280–286.
Constans, J., Viau, M., Gouaillard, C., and Clerc, A., 1981, Haptoglobin, polymorphism among Saharian and West African groups, Amer. J. Hum. Genet. 33: 606–616.
Cook, P. J. L., Gray, J. E., Brack, R. A., and Robson, E. B., 1969, Data on haptoglobin and the D group chromosomes, Ann. Hum. Genet. 33: 125–138.
de Castro, I., Cormier, F., and Waks, M., 1970, Haptoglobin porto alegre, Protides of the Biological Fluids 18: 373–376.
Dixon, G. H. 1966, Mechanisms of protein evolution, in: Essays in Biochemistry (P. N. Campbell and G. C. Greville, eds.), Academic Press, New York.
Dobryszycka, W., and Osada, J., 1977, Hybridization of human and porcine haptoglobins, Int. J. Biochem. 8: 511–515.
Doolittle, R. F., 1979, Protein evolution, in: The Proteins (H. Neurath and R. L. Hill, eds.), Vol. IV, pp. 1–118, Academic Press, New York.
Edman, P., and Sjöquist, J., 1956, Identification and semiquantitative determination of phenyl thiohydantoins, Acta Chem. Scand. 10: 1507–1509.
Eichman, K., Deicher, H., and Cleve, H., 1966, Immunologische Analyse der Beziehungen Zwischen den drei verschiedenen Typen von Antigendeterminanten normaler menschlicher Haptoglobine, Humangenetik 2: 271–286.
Emura, J., Ikenaka, T., Collins, J. H., and Schmid, K., 1971, The constant and variable regions of the carbonyl-terminal CNBr fragment of α1-acid glycoprotein, J. Biol. Chem. 246: 7821–7823.
Ferguson-Smith, M. A., and Aitken, D. A., 1978, Heterozygosity at the α-haptoglobin locus associated with a deletion, 16 q 22 → 16 qter, Cytogenet. Cell Genet. 22: 513.
Ferrell, R. E., Ueda, N., Satoh, C. Tanos, R. J., Neel, J. V., Hamilton, H. B., Inamizu, T., and Baba, K., 1977, The frequency in Japanese of genetic variants of 22 proteins. I. Albumin, ceruloplasmin, haptoglobin and transferrin, Ann. Hum. Genet. 40: 407–418.
Flory, L. L., 1963, Haptoglobin types of the Nez Perce Indians, Nature 197: 577–578.
Fuller, G. M., Rasco, M. A., McCombs, M. L., Barnett, D. R., and Bowman, B. H., 1973, Subunit composition of haptoglobin 2–2 polymers, Biochemistry 12: 253–258.
Galatius-Jensen, F., 1957, Further investigations of the genetic mechanism of the haptoglobins, Acta Genet. Stat. Med. 7: 549–564.
Galatius-Jensen, F., 1958, Rare phenotypes in the Hp system, Acta Genet. 8: 248–255.
Gerald, P. S., Warner, S., Singer, J. D., Corcorau, P. A., and Umansky, I., 1964, Possible identification of the chromosome bearing the haptoglobin locus, J. Clin. Invest. 43: 1297.
Giblett, E. R., 1959, Haptoglobin types in American negroes, Nature 183: 192–193.
Giblett, E. R., 1964, Variant haptoglobin phenotypes, Cold Spring Harbor Symp. Quant. Biol. 29: 321–326.
Giblett, E. R., 1968, The haptoglobin system, Series Haematol. 1: 3–20.
Giblett, E. R., 1969, Haptoglobin, in: Genetic Markers in Human Blood, F. A. Davis, Philadelphia, Pennsylvania.
Giblett, E. R., and Brooks, L. E., 1963, Haptoglobin subtypes in three racial groups, Nature 197: 576–577.
Giblett, E. R., and Steinberg, A. G., 1960, The inheritance of serum haptoglobin types in American negroes: Evidence for a third allele, Hp 2M, Am. J. Hum. Genet. 12: 160–169.
Giblett, E. R., Uchida, I., and Brooks, L. E., 1966, Two rare haptoglobin phenotypes, 1- B and 2-B, containing a previously undescribed α polypeptide chain, Am. J. Hum. Genet. 18: 448–453.
Gordon, S., and Bearn, A. G., 1966, Hemoglobin binding capacity of isolated haptoglobin polypeptide chains, Proc. Soc. Exp. Biol. Med. 121: 846–850.
Gordon, A. H., and Limaos, E. A., 1979a, Human blood and rabbit peritoneal leucocytes as sources of endogenous mediators, Br. J. Exp. Path. 60: 441–446.
Gordon, A. H., and Limaos, E. A., 1979b, Effects of bacterial endotoxin and corticosteroids on plasma concentrations of α2-macroglobulin, haptoglobin, and fibrinogen in rats, Br. J. Exp. Path. 60: 434–440.
Greer, J., 1980, Model for haptoglobin heavy chain based upon structural homology, Proc. Natl. Acad. Sci. USA 77(6): 3393–3397.
Guinand, S., Tonnelat, J., Bouissier, G., and Jayle, M.-F., 1956, Propriétés physiques de l’haptoglobine, séromucoide, et de sa combinaison hemoglobinique, Bull. Sec. Chim. Biol. 38: 329–341.
Hamaguchi, H., 1969, Purification and some properties of the three common genetic types of haptoglobins and the hemoglobin-haptoglobin complexes, Am. J. Hum. Genet. 21: 440–456.
Hardisty, R. M., Till, M. M., Lawler, S. D., Klouda, P. T., Batchelor, J. R., Edwards, J. H., Stuart, J., Cook, P. J. L., and Robson, E. B., 1971, Data on the linkage relationships of the HL-A and a-haptoglobin loci in man, Ann. Hum. Genet. 35: 161–166.
Harris, H., Robson, E. B., and Siniscalco, M., 1958, Atypical segregation of haptoglobin types in man, Nature 182: 1324–1325.
Harris, H., Lawler, S. D., Robson, E. B., and Smithies, O., 1960, The occurrence of two unusual serum protein phenotypes in a single pedigree, Ann. Hum. Genet. 24: 63–69.
Haugen, T. H., Hanley, J. M., and Heath, E. C., 1981, Haptoglobin: A novel mode of biosynthesis of a liver secretory glycoprotein, J. Biol. Chem. 256: 1055–1057.
Hecht, F., Blaine, T., Magenes, R. E., Kimberling, W. J., Wyandt, H., and Lovrien, E. W., 1971. Chromosomal localization of the heterochromatic region of 16 qh (.76) linked to a-haptoglobin in man, Nature 233: 480.
Hershko, C., Cook, J. D., and Finch, C. A., 1972, Storage ironkinetics II. The uptake of hemoglobin iron by hepatic parenchymal cells, J. Lab. Clin. Med. 80: 624–634.
Hewett-Emmett, D., Czelusniak, J., and Goodman, M., 1981, The evolutionary relationships of the enzymes involved in blood coagulation and hemostasis, in: Contributions to Hemostasis (D. A. Walz and L. E. McCoy, eds.), Ann. New York Acad. Sci., in press.
Hirayama, C., Nakamura, M., and Koga, S., 1975, Serum haptoglobin type and liver cirrhosis, Humangenetik 28: 139–146.
Hirschfeld, J., and Lunell, N.-O., 1962, Serum protein synthesis in foetus: Haptoglobins and group-specific components, Nature 196: 1220.
Hollowell, J. G., Littlefield, L. G., Dharm-krong-At, A., Folger, G. M., Heath, C. W., Jr., and Bloom, G. E., 1971, Ring 13 chromosome with normal haptoglobin inheritance, J. Med. Genet. 8: 222–226.
Howard, A., and Ansell, B. M., 1964, Vertical starch-gel electrophoresis in some rheumatic diseases, Ann. Rheum. Dis. 23: 232–235.
Hunt, L. T., and Dayhoff, M. O., 1970, The occurrence in proteins of the tripeptides Asn-x-Ser and Asn-x-Thr and of bound carbohydrate, Biochem. Biophys. Res. Commun. 39: 757–765.
Hwang, P. K., and Greer, J., 1980, Interaction between hemoglobin subunits in the hemoglobin · haptoglobin complex, J. Biol. Chem. 255: 3038–3041.
Ingram, V. M., 1957, Gene mutations in human haemoglobin: The chemical difference between normal and sickle cell haemoglobin, Nature 180: 326–328.
Ip, S. H. C., Johnson, M. L., and Ackers, G. K., 1976, Kinetics of deoxyhemoglobin subunit dissociation determined by haptoglobin binding: Estimation of the equilibrium constant from forward and reverse rates Biochemistry 15(3): 654–660.
Jarrett, I. G., 1972, A polymeric form of haemoglobin-binding protein in sheep following metabolic and hormonal disturbance, Aust. J. Biol. Sci. 25: 941–948.
Javid, J., 1965, The effect of haptoglobin polymer size on hemoglobin binding capacity, Vox Sang 10: 320–325.
Javid, J., 1967, 2–1 Bellevue, a haptoglobin β-chain mutant, Proc. Natl. Acad. Sci. 57: 920–924.
Javid, J., 1978, Human haptoglobins, Current Topics in Hematology 1: 151–192.
Javid, J., and Yingling, W., 1968a, Immunogenetics of human haptoglobin. I. The antigenic structure of normal Hp phenotypes, J. Clin. Invest. 47: 2290–2296.
Javid, J., and Yingling, W., 1968b, Immunogenetics of human haptoglobin. II. Hp Bellevue, a cross-reacting mutant, J. Clin. Invest. 47: 2297–2304.
Javid, J., Fischer, D. S., and Spaet, T. H., 1959, Inability of haptoglobin to bind myoglobin, Blood 14: 683–687.
Jayle, M.-F., and Gillard, P., 1947, Précipitation saline d’une protéine définie dans un mélange hétérogéné, Bull. Soc. Chim. Biol. 29: 149–157.
Jayle, M.-F., and Moretti, J., 1962, Haptoglobin: Biochemical, genetic and physiopathologic aspects, Prog. Hematol. 3: 342–359.
Jayle, M.-F., Boussier, G., and Tonnelat, J., 1956, Isolement a partir du sérum humain de la combinaison hémoglobine-haptoglobine a l’état homogéne, Bull. Soc. Chim. Biol. 38: 343–349.
John, D. W., and Miller, L. L., 1969, Regulation of net biosynthesis of serum albumin and acute phase plasma proteins, J. Biol. Chem. 244: 6134–6142.
Kan, Y. W., and Dozy, A. M., 1980, Evolution of the hemoglobin S and C genes in world population, Science 209: 388–391.
Kirk, R. L., 1968, The haptoglobin groups in man, in: Human Genetics Monographs, Vol. 4 (J. Beckman and M. Hauge, eds.), Karger, Basel.
Kirk, R. L., and Lai, L. Y. C., 1961, The distribution of haptoglobin and transferrin in South and Southeast Asia, Acta Genet. 11: 97–105.
Kirk, R. L., Kinns, H., and Morton, N. E., 1970, Interaction between the ABO blood groups and haptoglobin systems, Am. J. Hum. Genet. 22: 384–389.
Kodama, M. Hashimoto, K., and Matsuura, F., 1975, Studies on the haptoglobin of eel. I. Purification of haptoglobin, Bull. Jpn. Soc. Sci. Fish. 41: 1015–1019.
Koj, A., 1974, Acute-phase reactants, in: Structure and Function of Plasma Proteins (A. C. Allison, ed.), pp. 73–133, Plenum Press, New York.
Korngold, L., 1963, Antigenetic differences among human haptoglobins, Int. Arch. Allergy Appl. Immunol. 23: 268–280.
Kurachi, K., and Davie, E. W., 1977, Activation of human Factor XI (Plasma Thromboplastin Antecedent) by Factor XII2 (Activated Hageman Factor), Biochemistry 16: 5831–5839.
Kurnit, D. M., and Hoehn, H., 1979, Prenatal diagnosis of human genome variation, Ann. Rev. Genet. 13: 235–258.
Kurosky, A., 1980, Evolution of haptoglobin and the serine proteases, in: Protides of the Biological Fluids, Vol. 28 (H. Peeters, ed.), pp. 99–102, Pergamon Press, New York.
Kurosky, A., 1981, Amino acid sequence of dog haptoglobin α chain, In preparation.
Kurosky, A., Kim, H.-H., and Touchstone, B., 1976a, Comparative sequence analysis of the N-terminal region of rat, rabbit, and dog haptoglobin β-chains, Comp. Biochem. Physiol. 55B: 453–459.
Kurosky, A., Hay, R. E., Kim, H.-H., Touchstone, B., Rasco, M. A., and Bowman, B. H., 1976b, Characterization of the cyanogen bromide fragments of the β chain of human haptoglobin, Biochemistry. 15: 5326–5336.
Kurosky, A., Hay, R. E., and Bowman, B. H., 1979, Canine haptoglobin: A unique haptoglobin subunit arrangement, Comp. Biochem. Physiol. 62B: 339–344.
Kurosky, A., Barnett, D. R., Lee, T.-H., Touchstone, B., Hay, R. E., Arnott, M. S., Bowman, B. H., and Fitch, W. M., 1980, Covalent structure of human haptoglobin: A serine protease homolog, Proc. Natl. Acad. Sci. USA. 77: 3388–3392.
Latner, A. L., and Zaki, A. H., 1960, Clinical uses of starch gel electrophoresis with special reference to leukemia, Clin. Chim. Acta 5: 22–25.
Laurell, C. B., and Nyman, M., 1958, Haptoglobin als Haemoglobintransportar in Plasma, in: Protides of the Biological Fluids (H. Peeters, ed.), p. 195, Elsevier, Amsterdam.
Lockhart, W. L., and Smith, D. B., 1971, Effect of maleylation and amidination of hemoglobin on its haptoglobin and oxygen reactions, Can. J. Biochem. 49: 148–153.
Lombart, C., Moretti, J., and Jayle, M. F., 1965, Préparation et propriétés physiques des haptoglobines de lapin et de rat, Biochim. Biophys. Acta 97: 262–269.
Lombart, C., Musquera, S., and Delers, F., 1979, Characterization and specific properties of chicken haptoglobin, in: XIth International Congress of Biochemistry, Toronto, p. 178.
Magenis, R. E., Hecht, F., and Lovrien, E. W., 1970, Heritable fragile site in chromosome 16: Probable localization of haptoglobin locus in man, Science 170: 85–87.
Magnusson, S., Peterson, T. E., Sottrup Jensen, L., and Claeys, H., 1975, Complete primary structure of prothrombin: Isolation, structure and reactivity of ten carboxylated glutamic acid residues and regulation of prothrombin activation by thrombin, in: Proteases and Biological Control, Cold Spring Harbor Conference on Cell Proliferation (E. Reich, D. B. Rifkin, and E. Shaw, eds.), Vol. 2, pp. 123–149.
Makinen, M. W., Milstein, J. B., and Kon, H., 1972, Specificity of interaction of haptoglobin with mammalian hemoglobin, Biochemistry 11: 3851–3860.
Malchy, B., and Dixon, G. H., 1970, The resemblance of the combination of human haptoglobin and double hemoglobin molecules to an antigen-antibody reaction, Can. J. Biochem. 48: 192–197.
Malchy, B., and Dixon, G. H., 1973a, Studies on the interchain disulfides of human haptoglobins, Can. J. Biochem. 51: 249–264.
Malchy, B., and Dixon, G. H., 1973b, Correction to the amino acid sequence of the a chain of human haptoglobin, Can. J. Biochem. 51: 321–322.
Mancini, G., Carbonara, A. O., and Heremans, J. F., 1965, Immunochemical quantitation of antigens by single radial immunodiffusion, Immunochem. 2: 235–254.
Marnay, A., 1961, Haptoglobinuria in nephrotic syndromes, Nature 191: 74–75.
Matson, G. A., Sutton, H. E., Swanson, J., and Robinson, A., 1966, Distribution of hereditary blood groups in South America. I. In Ecuador, Am. J. Physiol. Anthropol. 24: 51–70.
Matsunaga, A., Murai, K., and Matsuda, E., 1962, Inheritance of haptoglobin types in 51 Japanese families, Acta Genet. Stat. Med. 12: 262–280.
Matsunaga, E., Omoto, K., Shinoda, T., Matsuda, E., and Oishi, H., 1970, A further study on the family with anomalous inheritance of haptoglobin types, Jpn. J. Hum. Genet. 15: 166–175.
McCombs, M. L., and Bowman, B. H., 1969, Demonstration of inherited ceruloplasmin variants in human serum by acrylamide electrophoresis, Tex. Rep. Biol. Med. 27: 769–772.
Mikes, O., Holeysovsky, V., Tomasek, V., and Sorm, F., 1966, Covalent structure of bovine trypsinogen. The position of the remaining amides, Biochem. Biophys. Res. Commun. 24: 346–352.
Miller, L. L., and John, D. W., 1969, Regulation of net biosynthesis of serum albumin and acute phase plasma proteins, J. Biol. Chem. 244: 6134–6142.
Mohr, J., 1966, Genetics of fourteen marker systems: Associations and linkage relations, Acta Genet. Stat. Med. 16: 1–58.
Moore, S., Spackman, D. H., and Stein, W. H., 1958, Chromatography of amino acids on sulfonated poly styrene resins—An improved system, Anal. Chem. 30: 1185–1190.
Morganti, G., Beolchini, P. E., Vierucci, A., and Butler, R., 1968, Contribution to the genetics of the serum β-lipoproteins in man: III. Lack of association and linkage between the Ag(x, y, a) factors and some blood and serum protein antigens, Humangenetik 6: 275–278.
Morrell, A. G., Gregoriadis, G., Scheinberg, I. H., Hickman, J., and Ashwell, G., 1971, The role of sialic acid in determining the survival of glycoproteins in the circulations, J. Biol. Chem. 246: 1461–1467.
Muller, H. J., 1922, Variation due to change in the individual gene, Am. Naturalist 56: 32–50.
Murray, R. F., Jr., Robinson, J. C., and Visnich, S., 1966, Observations on the inheritance of hypohaptoglobinemia, Acta Genet. 16: 113–121.
Musquera, S., Lombart, C., Jayle, M.-F., Rogard, M., and Waks, M., 1979, Identification of haptoglobin in chicken serum and specificity of the chicken haptoglobin-hemoglobin complex formation, Comp. Biochem. Physiol. 62B: 241–244.
Nagel, R. L., and Gibson, Q. H., 1971, The Binding of hemoglobin to haptoglobin and its relation to subunit dissociation of hemoglobin, J. Biol. Chem. 246: 69–73.
Nagel, R. L., and Gibson, Q. H., 1972, The hemoglobin-haptoglobin reaction as a probe of hemoglobin conformation, Biochem. Biophys. Res. Commun. 48: 959–966.
Nagel, R. L., and Ranney, H. M., 1964, Haptoglobin binding capacity of certain abnormal hemoglobins, Science 144: 1014–1015.
Nagel, R. L., Rothman, M. C., Bradley, T. B., Jr., and Ranney, H. M., 1965, Comparative haptoglobin binding properties of oxyhemoglobin and deoxyhemoglobin, J. Biol. Chem. 240: 4543–4545.
Naik, S. N., Ishwad, C. S., Nadkarni, J. S., Nadkarni, J. J., and Advani, S. H., 1979, Study of haptoglobin polymorphism and its significance in human leukemias, Eur. J. Cancer 15: 1463–1469.
Naito, S., 1967, Type-dependent difference in the clearance rate of hemoglobin-haptoglobin complexes from the blood streams, Jpn. J. Hum. Genet. 12: 177–186.
Nakajima, H., Takemura, T., Nakajima, O., and Yamaoka, K., 1963, Studies of heme α-methenyl oxygenase, J. Biol. Chem. 238: 3784–3796.
Nance, W. E., and Smithies, O., 1963, New haptoglobin alleles: A prediction confirmed, Nature 198: 869–870.
Nance, W. E., Empson, J. E., and Bennett, T. W., 1968, Haptoglobin and catalase loci in man: Possible genetic linkage, Science 160: 1230–1231.
Nyman, M., 1959, Serum haptoglobin: Methodological and clinical studies, Scand. J. Clin. Lab. Inv. 11(Suppl. 39): 1–169.
O’Farrell, P. H., and Ivarie, R. D., 1978, The glucocorticoid domain: Steroid-mediated changes in the rate of synthesis of rat hepatoma proteins, Cell 13: 41–55.
Ofosu, F., 1971, Structural studies on human haptoglobin, Ph.D. Dissertation, University of Toronto.
Ogawa, A., Kagiyama, S., Kawamura, K., and Yanase, T., 1970, Studies on human haptoglobins. V. Isolation and physico-chemical characterization of the hemoglobin-haptoglobin 2–1 complexes, Proc. Jpn. Acad. 46: 814–819.
Op den Weide, W., and Stam, F. C., 1973, Haptoglobin types and subtypes in Alzheimer’s disease and senile dementia, Humangenetik 20: 25–30.
Pagano, M. R., Engler, R., Gelin, M., and Jayle, M.-F., 1980, Kinetic study of the interaction between rat haptoglobin and rat liver cathepsin B, Can. J. Biochem. 58: 410–417.
Painter, T. S., 1933, A new method for the study of chromosome rearrangements and plotting of chromosome maps, Science 78: 585–586.
Parker, W. C., and Bearn, A. G., 1963, Control gene mutation as a possible explanation of certain haptoglobin phenotypes, Am. J. Hum. Genet. 15: 159–181.
Pastewka, J. V., Ness, A. T., and Peacock, A. C., 1975, Hemoglobin binding by isolated polymeric proteins from human haptoglobin types 2–1 and 2–2. Some suggested polymer subunit compositions, Biochim. Biophys. Acta 386: 530–537.
Peacock, A. C., 1966, Serum haptoglobin type and leukemia: An association with possible etiological significance, J. Nat. Cancer Inst. 36: 631–639.
Peacock, A. C., and Alepa, F. P., 1966, Haptoglobin types in patients with juvenile rheumatoid arthritis, Ann. Rheum. Dis. 25: 567–569.
Peacock, A. C., Bunting, L. S., and Queen, K. G., 1965, Serum protein electrophoresis in acrylamide gel: Patterns from normal human subjects, Science 147: 1451–1453.
Peacock, A. C., Pastewka, J. V., Reed, R. A., and Ness, A. T., 1970, Haptoglobin-hemoglobin interaction. Stoichiometry, Biochemistry 9: 2275–2279.
Pintera, J., 1971, The biochemical, genetic, and clinicopathological aspects of haptoglobin, in: Series Haematologica, Vol. IV (K. G. Jensen and S.-A. Killmann, eds.), Munksgaard, Copenhagen.
Pintera, J., Dvorak, R., Vacl, J., and Fiser, J., 1969, A haptoglobin Johnson family with non-hypohaptoglobinemic Hp J/HP2, J. Med. Genet. 6: 187–189.
Pironneau, F., Sternberg, M., Moisy, M., Feret, J., Rebeyrotte, P., Lagrue, G., and Jayle, M.-F., 1974, Orosomucoid and haptoglobin excretion in rat glomerulonephritis and tubulonephrites, Nephron 13: 434–442.
Polonovski, M., and Jayle, M.-F., 1938, Existence dans le plasma sanguin d’une substance activant l’action peroxydasique de l’hémoglobine, C.R. Soc. Biol. 129: 457–460.
Polonovski, M., and Jayle, M.-F., 1939, Peroxydases animales. Leur spécificité et leur role biologique, Bull. Soc. Chim. Biol., Paris 21: 66–91.
Polonovski, M., and Jayle, M.-F., 1940, Chimie Biologique—Sur la préparation d’une nouvelle fraction des protéines plasmatiques, l’haptoglobine, C.R. Acad. Sci. 211: 517–520.
Prokop, O., and Köhler, W., 1978, Haptoglobins are antibody-like proteins, Z. Immun. Forsch. 154: 407–408.
Putnam, F. W., 1975, Haptoglobin, in: The Plasma Proteins, Structure, Function, and Genetic Control, 2nd. ed. (F. W. Putnam, ed.), Vol. 2, pp. 1–50, Academic Press, New York.
Rausen, A. R., Gerald, P. S., and Diamond, L. K., 1961, Haptoglobin patterns in cord blood serums, Nature 191: 717.
Reichlin, M., Udem, L., and Ranney, H. M., 1969, The effect of specific antibody on the oxygen equilibrium of human hemoglobin, Biochim. Biophys. Acta 175: 49–54.
Renwick, J. H., and Marshall, H., 1966, A new type of human haptoglobin, Hp 2–1D, Ann. Hum. Genet. 29: 389–390.
Ritter, H., and Hinkelmann, Z., 1966, Zur Balance des Polymorphismus der Haptoglobine, Humangenetik 2: 21–24.
Ritter, H. and Schmitt, J., 1971, Hp 2–2 like phenotypes in mammals, Humangen. 12: 351–353.
Robert, L. V., Boussier, G., and Jayle, M.-F., 1957, Groupements sulfhydriques de l’haptoglobine et de sa combinaison hémoglobinique, Experientia 13: 111–112.
Robson, E. B., Glen-Bott, A. M., Cleghorn, T. E., and Harris, H., 1964, Some rare haptoglobin types, Ann. Hum. Genet. 28: 77–85.
Robson, E. B., Polani, P. E., Dart, S. J., Jacobs, P. A., and Renwick, J. H., 1969, Probable assignment of the alpha locus of haptoglobin to chromosome 16 in man, Nature 223: 1163–1165.
Rogard, M., and Waks, M., 1977, Studies on hemoglobin tryptophanyl contact residues in the haptoglobin · hemoglobin complex, Eur. J. Biochem. 77: 367–373.
Rougemont, A., Quilici, M., Delmont, J., and Ardissone, J. P., 1980, Is the Hp0 phenomenon in tropical populations really genetic?, Hum. Hered. 30: 201–203.
Rupp, R. G., and Fuller, G. M., 1979, The effects of leucocytic and serum factors on fibrinogen biosynthesis in cultured hepatocytes, Exp. Cell Res. 118: 23–30.
Saeed, S. A., Kendall, P. A., McDonald-Gibson, W. J., and Collier, H. O. J., 1978, Haptoglobin concentration and the activity of an endogenous inhibitor of prostaglandin synthetase in blood plasma, Biochem. Soc. Trans. 6: 1166–1169.
Sasazuki, T., 1971, Immunochemical and physicochemical properties of haptoglobin, antihemoglobin antibody and their complexes with hemoglobin, Immunochem. 8: 695–704.
Sasazuki, T., Tsunoo, H., and Nakajima, H., 1973, Studies on haptoglobin. VI. Effects of anti-hemoglobin antibody on the peroxidase activity and acid denaturation of hemoglobin, Proc. Jpn. Acad. 49: 358–361.
Schultze, H. E., and Heremans, J. F., 1966, Molecular variation in haptoglobin, in: Molecular Biology of Human Proteins, Vol. 1, Nature and Metabolism of Extracellular Proteins, pp. 383–402, Elsevier, Amsterdam.
Schultze, H. E., Haupt, H., Heide, K., and Heimburger, N., 1963, Über Die Chemie des Haptoglobin-Polymorphismus, Clin. Chim. Acta 8: 207–214.
Segrest, J. P., Jackson, R. L., Andrews, E. P., and Marchesi, V. T., 1971, Human erythrocyte membrane glycoprotein: A re-evaluation of the molecular weight as determined by SDS polyacrylamide gel electrophoresis, Biochem. Biophys. Res. Commun. 44: 390–408.
Sheridan, J. W., Kendrick, K. G., and Margolis, J., 1969, Phenotypic expression of the Hp 2-Hp 1 genotype, Biochem. Biophys. Res. Commun. 35: 474–477.
Shim, B.-S., 1976, Increase in serum haptoglobin stimulated by prostoglandins, Nature 259: 326–327.
Shin, B.-S., and Bearn, A. G., 1964, The distribution of haptoglobin subtypes in various populations, including subtype patterns in some non-human primates, Am. J. Hum. Genet. 16: 477–483.
Shim, B.-S., Lee, T.-H., and Kang, Y.-S., 1965, Immunologic and biochemical investigations of human serum haptoglobins: Composition of haptoglobin-haemoglobin intermediate, haemoglobin binding sites and presence of additional alleles for β chain, Nature 207: 1264–1267.
Shim, B.-S., Jin, K.-S., and Cleve, H., 1967, Immunologic reactivity of haptoglobin Marburg: Evidence for a beta chain mutation, Proc. Soc. Exp. Biol. Med. 126: 221–224.
Shinton, N. K., Richardson, R. W., and Williams, J. D. F., 1965, Diagnostic value of haptoglobin, J. Clin. Path. 18: 114–118.
Smithies, O., 1955, Zone electrophoresis in starch gels: Group variations in the serum proteins of normal human adults, Biochem. J. 61: 629–641.
Smithies, O., 1959, Zone electrophoresis in starch gels and its application to studies of serum proteins, Adv. Protein Chem. 14: 65–113.
Smithies, O., 1964, Chromosomal rearrangements and protein structure, Cold Spring Harbor Symp. Quant. Biol. 29: 309–319.
Smithies, O., and Walker, N. F., 1955, Genetic control of some serum proteins in normal humans, Nature 176: 1265–1266.
Smithies, O., and Walker, N. F., 1956, Notation for serum-protein groups and the genes controlling their inheritance, Nature 178: 694–695.
Smithies, O., Connell, G.E., and Dixon, G. H., 1962a, Inheritance of haptoglobin subtypes, Am. J. Hum. Genet. 14: 14–21.
Smithies, O., Connell, G. E., and Dixon, G. H., 1962b, Chromosomal rearrangements and evolution of haptoglobin genes, Nature 196: 232–236.
Snellman, O., and Sylvén, B., 1967, Haptoglobin acting as a natural inhibitor of cathepsin B activity, Nature 216: 1033.
Sottrup-Jensen, L., Claeys, H., Zajdel, M., Peterson, T. E., and Magnusson, S., 1978, The primary structure of human plasminogen: Isolation of two lysine-binding fragments and one “mini”-plasminogen (MW, 38,000) by elastase-catalyzed-specific limited proteolysis, in: Progress in Chemical Fihronolysis and Thrombolysis (J. F. Davidson, R. M. Rowan, M. M. Samama, and P. C. Desnoyers, eds.), Vol. 3, pp. 191–209, Raven, New York.
Stroud, R. M., Kay, L. M., and Dickerson, R. E., 1971, The crystal and molecular structure of DIP-inhibited bovine trypsin at 2.7 A resolution, Cold Spring Harbor Symp. Quant. Biol. 36: 125–140.
Sturtevant, A. H., 1925, The effects of unequal crossing over at the Bar locus in Drosophila, Genetics 10: 117–147.
Sutton, H. E., 1970, The haptoglobins, in: Progress in Medical Genetics, Vol. 7 (A. G. Steinberg and A. G. Bearn, eds.), pp. 163–216, Grune and Stratton, New York.
Sutton, H. E., and Karp, G. W., 1964, Variations of heterozygous expression at the haptoglobin locus, Am. J. Hum. Genet. 16: 419–434.
Tattrie, B. L., and Connell, G. E., 1967, Free sulfhydryl groups in haptoglobin, Can. J. Biochem. 45: 551–556.
Teisberg, P., and Gjone, E., 1974, Probable linkage of LCAT locus in man to the α haptoglobin locus on chromosome 16, Nature 249: 550–551.
Thymann, M., and Henningsen, K., 1975, Haptoglobin type Hρ-Jo and Hypohaptoglobinaemia in a Danish family, Hum. Hered. 25: 501–505.
Travis, J. C., and Sanders, B. G., 1972, Haptoglobin evolution: polymeric forms of Hp in the bovidal and cervidal families, J. Exp. Zool. 180: 141–148.
Travis, J. C., Brown, S. O., and Sanders, B. G., 1970, A polymeric form of haptoglobin in the gamma-irradiated Spanish goat, Biochem. Genet. 4: 639–649.
Travis, J. C., Garza, J., and Sanders, B. G., 1975, Structural characterization of polymeric haptoglobin from goats, Comp. Biochem. Physiol. 51B: 93–97.
Tsapis, A., Rogard, M., Alfsen, A., and Mihaesco, C., 1976, Binding of human hemoglobin and its polypeptide chains with haptoglobin coupled to an agarose matrix, Eur. J. Biochem. 64: 369–372.
Tsapis, A., Mihaesco, C., Alfsen, A., Beuzard, Y., and Rosa, J., 1978, Protein-protein interactions: Possible location of hemoglobin-haptoglobin contacts, Biochem. Biophys. Res. Commun. 80: 319–326.
Valette, I., Waks, M., Wejman, J. C., Arcoleo, J. P., and Greer, J., 1981, Haptoglobin heavy and light chains. Structural properties, reassembly, and formation of minicomplex with hemoglobins, J. Biol. Chem., In press.
Vana, L. R., and Steinberg, A. G., 1975, Haptoglobin-ABO interaction: A possible explanation for the excess of Hp1 among offspring of ABO incompatible matings, Am. J. Hum. Genet. 75: 224–232.
Voelkel, E. F., Levine, L., Alper, C. A., and Tashjian, A. H., 1978, Acute phase reactants, ceruloplasmin and haptoglobin and their relationship to plasma prostaglandins in rabbits bearing the V52 carcinoma, J. Exp. Med. 147: 1078–1088.
Wagener, D. K., and Cavalli-Sforza, L. L., 1975, Ethnic variation in genetic disease: Possible roles of hitchhiking and epistasis, Am. J. Hum. Genet. 27: 348–364.
Waks, M., and Beychok, S., 1974, Induced conformational states in human apohemoglobin on binding of haptoglobin 1–1. Effect of added heme as a probe of frozen structures, Biochemistry 13: 15–22.
Waks, M., deCastro, I., Lavialle, I., Beuzard, Y., Rosa, J., and Alfsen, A., 1971, Haptoglobin Porto Alegre: A new haptoglobin with anomalous hemoglobin-binding properties, Fed. Proc. 30: 1071.
Waks, M., Rogard, M., and Cittanova, N., 1978, The association equilibrium between haptoglobin and apohemoglobin, Biochem. Biophys. Res. Commun. 80: 252–258.
Walz, D. A., Hewett-Emmett, D., and Seegers, W. H., 1977, Amino acid sequence of human prothrombin fragments 1 and 2, Proc. Natl. Acad. Sci. USA 74: 1969–1972.
Wendt, G. G., Kruger, J., and Kindermann, I., 1968, Serumgruppen und Krankheit, Humangenetik 6: 281–299.
Wiman, B., 1977, Primary structure of the β-chain of human plasmin, Eur. J. Biochem. 76: 129–137.
Yang, H. J., and Przybylska, M., 1973, The microheterogeneity of human haptoglobin and its complex with hemoglobin, Can. J. Biochem. 51: 597–605.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1982 Plenum Press, New York
About this chapter
Cite this chapter
Bowman, B.H., Kurosky, A. (1982). Haptoglobin: The Evolutionary Product of Duplication, Unequal Crossing Over, and Point Mutation. In: Harris, H., Hirschhorn, K. (eds) Advances in Human Genetics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-8315-8_3
Download citation
DOI: https://doi.org/10.1007/978-1-4615-8315-8_3
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4615-8317-2
Online ISBN: 978-1-4615-8315-8
eBook Packages: Springer Book Archive