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Hb F in sickle cell anemia

  • Multi-author Reviews
  • Developments in Sickle Cell Anemia Research, Part I
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Abstract

We have reviewed the methodology for an accurate quantitation of Hb F in the blood of patients with sickle cell anemia, values observed in hundreds of patients of different (racial or ethnic) backgrounds and with differences in severity of the disease, and the various factors that affect the level of Hb F. The latter include sex, age, genetic background or chromosomal haplotypes, variations in the sequences of the locus control region(s) 5′ to the ε-globin gene, and the presence of an α chain deficiency or α-thalassemia. Finally, a few remarks about agents effective in increasing the in vivo Hb F synthesis are also included.

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References

  1. Abraham, E. C., Carver, J., Döbler, J., Milner, P. F., and Huisman, T. H. J., Microchromatographic quantitation of fetal hemoglobin in patients with sickle cell disease. Hemoglobin3 (1979) 341–351.

    PubMed  Google Scholar 

  2. Adekile, A. D., Kitundu, M. N., Liu, J-S., Gu, L-H., Adeodu, O. O., and Huisman, T. H. J., Haplotypes in SS patients from Nigeria; characterization of one atypical βs haplotype #19 (Benin) associated with elevated Hb F andGγ levels. Ann. Hemat.65 (1992) 41–45.

    Article  Google Scholar 

  3. Adekile, A. D., Liu, J-S., Gu, L-H., and Huisman, T. H. J., α-Thalassemia among SS patients from Nigeria. Hemoglobin (1992), submitted.

  4. Aluoch, J. R., Killinç, Y., Aksoy, M., Yüregir, G. T., Bakioglu, I., Kutlar, A., Kutlar, F., and Huisman, T. H. J., Sickle cell anaemia among Eti-Turks; haematological, clinical and genetic observations. Br. J. Haemat.64 (1986) 45–55.

    Google Scholar 

  5. Antonarakis, S. E., Boehm, C. D., Serjeant, G. R., Theisen, C. E., Dover, G. J., and Kazazian, H. H. Jr., Origin of the βs globin gene in Blacks; the contribution of recurrent mutation or gene conversion or both. Proc. natl Acad. Sci. USA81 (1984) 853–856.

    PubMed  Google Scholar 

  6. Ballas, S. K., Dover, G. J., and Charache, S., Effect of hydroxyurea on the rheological properties of sickle erythrocytes on hemoglobin F production and water content in the red blood cells of dogs and of patients with sickle cell anemia. Blood78 (1991) 216–221.

    Google Scholar 

  7. Ballas, S. K., Talacki, A., Adachi, K., Schwartz, E., Surrey, S., and Rappaport, E., The Xmn I site (−158, C → T) 5′ to theGγ gene: Correlation with the Senegalese haplotype andGγ globin expression. Hemoglobin15 (1991) 407–417.

    PubMed  Google Scholar 

  8. Behe, M. J., and Englander, S. W., Mixed gelation theory. Kinetics, equilibrium and gel incorporation in sickle hemoglobin mixtures. J. molec. Biol.133 (1979) 137–160.

    Article  PubMed  Google Scholar 

  9. Behringer, R. R., Ryan, T. M., Palmiter, R. D., Brinster, R. L., and Townes, T. M., Human γ- to β-gene switching in transgenic mice. Gene Develop.4 (1990) 380–389.

    Google Scholar 

  10. Benesch, R. E., Edalji, R., Benesch, R., and Kwong, S., Solubilization of hemoglobin S by other hemoglobins. Proc. natl Acad. Sci. USA77 (1980) 5130–5134.

    PubMed  Google Scholar 

  11. Berg, P. E., Williams, D. M., Quian, R. L., Cohen, R. B., Cao, S. X., Mittelman, M., and Schechter, A. N., A common protein binds to two silencers 5′ to the human β-globin gene. Nucleic Acids Res.17 (1989) 8833–8852.

    PubMed  Google Scholar 

  12. Bertles, J. F., and Milner, P. F., Irreversibly sickle erythrocytes: A consequence of the heterogeneous distribution of hemoglobin types in sickle cell anemia. J. clin. Invest.47 (1968) 1731–1741.

    PubMed  Google Scholar 

  13. Betke, K., Marti, H. R., and Schlicht, I., Estimation of small percentages of foetal haemoglobin. Nature184 (1959) 1877–1878.

    PubMed  Google Scholar 

  14. Bissé, E., and Wieland, H., High-performance liquid chromatographic separation of human haemoglobins-Simultaneous quantitation of foetal and glycated haemoglobins. J. Chromat.434 (1988) 95–110.

    Google Scholar 

  15. Boyer, S. H., Belding, T. K., Margolte, L., and Noyes, A. N., Fetal hemoglobin restriction to a few erythrocytes (F cells) in normal human adults. Science188 (1975) 361–363.

    PubMed  Google Scholar 

  16. Carterina, J. J., Ryan, T. M., Pawlik, K. M., Palmiter, R. D., Brinster, R. L., Behringer, R. R., and Townes, T. M., Human β-globin locus control region: Analysis of the 5′ DNase I hypersensitivity site HS-2 in transgenic mice. Proc. natl Acad. Sci. USA88 (1991) 1626–1630.

    PubMed  Google Scholar 

  17. Charache, S., Fetal hemoglobin, sickling and sickle cell disease. Adv. Pediatr.37 (1990) 1–31.

    PubMed  Google Scholar 

  18. Charache, S., Dover, G., Smith, K., Talbot, C. C. Jr, Moyer, M., and Boyer, S., Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the γ-δ-β-globin gene complex. Proc. natl Acad. Sci. USA80 (1983) 4842–4846.

    PubMed  Google Scholar 

  19. Cheetham, R. C., Huehns, E. R., and Rosemeyer, M. A., Participation of hemoglobins A, F, A2 and C in polymerization of hemoglobin S. J. molec. Biol.129 (1979) 45–61.

    Article  PubMed  Google Scholar 

  20. Constantoulakis, P., Josephson, B., Mangahas, L., Papayannopoulou, Th., Enver, T., Constantini, F., and Stamatoyannopoulos, G., Locus control region-Aγ transgenic mice: A new model for studying the induction of fetal hemoglobin in the adult. Blood77 (1991) 1326–1333.

    PubMed  Google Scholar 

  21. Curtin, P. T., Liu, D., Liu, W., Chang, J. C., and Kan, Y. W., Human α-globin gene expression in transgenic mice is enhanced by a distant DNase I hyper-sensitive site. Proc. natl Acad. Sci. USA86 (1989) 7082–7086.

    PubMed  Google Scholar 

  22. Dimovski, A. J., Oner, C., Agarwal, S., Gu, Y-C., Gu, L-H., Kutlar, F., Lanclos, K. D., and Huisman, T. H. J., Certain mutations observed in the 5′ sequences of theGγ- andAγ-globin genes of βs chromosomes are specific for chromosomes with major haplotypes. Acta haemat.85 (1991) 79–87.

    PubMed  Google Scholar 

  23. Dover, G. J., Boyer, S. H., and Bell, W. R., Microscopic method for assaying F cell production: Illustrative changes during infancy and in aplastic anemia. Blood52 (1978) 664–672.

    PubMed  Google Scholar 

  24. Dover, G. J., Boyer, S. H., and Pembrey, M. E., F cell production in sicle cell anemia; regulation by genes linked to β-hemoglobin locus. Science211 (1981) 1441–1444.

    PubMed  Google Scholar 

  25. Dover, G. J., Chang, V. T., Boyer, S. H., Serjeant, G. R., Antonarakis, S. E., and Higgs, D. R., The cellular basis for different fetal hemoglobin levels among sickle cell individuals with two, three and four α-globin genes. Blood69 (1987) 341–344.

    PubMed  Google Scholar 

  26. Economou, E. P., Antonarakis, S. E., Kazazian, H. H. Jr, Serjeant, G. R., and Dover, G. J., Variation in Hemoglobin F production among normal and sickle cell adults is not related to nucleotide substitution in the γ promoter regions. Blood77 (1991) 174–177.

    PubMed  Google Scholar 

  27. Efremov, G. D., Gjorgovski, I., Stojanovski, N., Diaz-Chico, J. C., Harano, T., Kutlar, F., and Huisman, T. H. J., One haplotype is associated with the Swiss type of hereditary persistence of fetal hemoglobin in the Yugoslavian population. Hum. Genet.77 (1987) 132–136.

    Article  PubMed  Google Scholar 

  28. Elion, J., Berg, P. E., Trabuchet, G., Schechter, A. N., Krishnamoorthy, R., and Labic, D., Is polymorphism 0.5 kb 5′ to the β-globin gene relevant toGγ- andAγ-globin genes of βs gene expression? Blood74 (1989) 143a (Suppl. 1).

    Google Scholar 

  29. Enver, T., Raich, N., Ebens, A. J., Papayannopoulou, Th., Constantini, F., and Stamatoyannopoulos, G., Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice. Nature344 (1990) 309–313.

    Article  PubMed  Google Scholar 

  30. Fabry, M. E., Mears, J. G., Patel, P., Schaefer-Rego, K., Carmichael, L. D., Martinez, G., and Nagel, R. L., Dense cells in sickle cell anemia: The effects of gene interaction. Blood64 (1984) 1042–1046.

    PubMed  Google Scholar 

  31. Forrester, W. C., Thompson, C., Elder, J. T., and Groudine, M., A developmentally stable chromatin structure in the human β-globin gene cluster. Proc. natl Acad. Sci. USA83 (1986) 1359–1363.

    PubMed  Google Scholar 

  32. Fraser, P., Hurs, J., Collis, P., and Grosveld, F., DNase I hypersensitive sites 1, 2 and 3 of human β-globin dominant control region direct position-independent expression. Nucleic Acids Res.18 (1990) 3503–3508.

    PubMed  Google Scholar 

  33. Gilman, J. G., and Huisman, T. H. J., DNA sequence variation associated with elevated fetalGγ globin production. Blood66 (1985) 783–787.

    PubMed  Google Scholar 

  34. Gilman, J. G., and Huisman, T. H. J., A mutation associated with elevatedGγ chain in sickle cell anemia and hereditary persistence of fetal hemoglobin, in: Progress in Clinical and Biological Research, vol. 191. Experimental Approaches for the Study of Hemoglobin Switching, pp. 141–149. Eds G. Stamatoyannopoulos and A. W. Nienhuis. Alan R. Liss, Inc., New York 1985.

    Google Scholar 

  35. Goldberg, M. A., Brugnara, C., Dover, G. J., Schapira, L., Charache, S., and Bunn, H. F., Treatment of sickle cell anemia with hydroxyurea and erythropoietin. N. Engl. J. Med.323 (1990) 366–372.

    PubMed  Google Scholar 

  36. Goldberg, M. A., Husson, M. A., and Bunn, H. F., Participation of hemoglobins A and F in polymerization of sickle hemoglobin. J. biol. Chem.252 (1977) 3414–3421.

    PubMed  Google Scholar 

  37. Gonzalez-Redondo, J. M., Stoming, T. A., Lanclos, K. D., Gu, Y. C., Kutlar, A., Kutlar, F., Nakatsuji, T., Deng, B., Han, I. S., McKie, V. C., and Huisman, T. H. J., Clinical and genetic heterogeneity in Black patients with homozygous β-thalassemia from the Southeastern United States. Blood72 (1988) 1007–1014.

    PubMed  Google Scholar 

  38. Grosveld, F., Blom van Assendelf, G., Greaves, D. R., and Kollias, G., Position-independent, high level expression of the human β-globin gene in transgenic mice. Cell51 (1987) 975–985.

    Article  PubMed  Google Scholar 

  39. Gupta, R. B., Tiwary, R. S., Pande, P. L., Kutlar, F., Öner, C., Öner, R., and Huisman, T. H. J., Hemoglobinopathies among the Gond tribal groups of Central India; interaction of α and β thalassemia with β chain variants. Hemoglobin15 (1991) 441–458.

    PubMed  Google Scholar 

  40. Hattori, Y., Kutlar, F., Kutlar, A., McKie, V. C., and Huisman, T. H. J., Haplotypes of βs chromosomes among patients with sickle cell anemia from Georgia. Hemoglobin10 (1986) 623–642.

    PubMed  Google Scholar 

  41. Hattori, Y., Kutlar, F., Mosley, C. J., Mayson, S. M., and Huisman, T. H. J., Association of the level ofGγ chain in the fetal hemoglobin of normal adults with specific haplotypes. Hemoglobin10 (1986) 185–204.

    PubMed  Google Scholar 

  42. Higgs, D. R., Vickers, M. A., Wilkie, A. O. M., Pretorious, I-M., Jarman, A. P., and Weatherall, D. J., A review of the molecular genetics of the human α-globin gene. Blood73 (1989) 1081–1104.

    PubMed  Google Scholar 

  43. Hofrichter, J., Ross, P. D., and Eaton, W. A., Kinetics and mechanism of deoxyhemoglobin S gelation: A new approach to understanding of sickle cell disease. Proc. natl Acad. Sci. USA71 (1974) 4864–4868.

    PubMed  Google Scholar 

  44. Huisman, T. H. J., Separation of hemoglobins and hemoglobin chains by high-performance liquid chromatography. J. Chromat.418 (1987) 277–304.

    Google Scholar 

  45. Huisman, T. H. J., and Jonxis, J. H. P., The Hemoglobinopathies Techniques of Identification, vol. 6. Clinical and Biochemical Analysis. Marcel Dekker, Inc., New York 1977.

    Google Scholar 

  46. Huisman, T. H. J., and Schroeder, W. A., New aspects of the structure, function and synthesis of hemoglobins, in: CRC Critical Reviews in Clinical Laboratory Science, pp. 471–526. CRC Press, Inc., Boca Raton, FL 1970.

    Google Scholar 

  47. Kaul, D. K., Fabry, M. E., Windisch, P., Baez, S., and Nagel, R. L., Erythrocytes in sickle cell anemia are heterogeneous in their rheological and hemodynamic characteristics. J. clin. Invest.72 (1983) 23–31.

    Google Scholar 

  48. Kleihauer, E., Braun, H., and Betke, K., Demonstration von fetalem Hämoglobin in den Erythrozyten eines Blutausstrichs. Klin. Wochenschr.35 (1957) 637.

    Article  PubMed  Google Scholar 

  49. Kutlar, A., Hattori, Y., Bakioglu, I., Kutlar, F., Kamel, K., and Huisman, T. H. J., Hematological observations on Arabian SS patients with a homozygosity or heterozygosity for a βs chromosome with haplotype No. 31. Hemoglobin9 (1985) 545–557.

    PubMed  Google Scholar 

  50. Kutlar, A., Kutlar, F., Gu, L-G., Mayson, S. M., and Huisman, T. H. J., Fetal hemoglobin in normal adults and β-thalassemia heterozygotes. Hum. Genet.85 (1990) 106–110.

    Article  PubMed  Google Scholar 

  51. Kutlar, F., Kutlar, A., and Huisman, T. H. J., Separation of normal and abnormal hemoglobin chains by reversed-phase high-performance liquid chromatography. J. Chromat.357 (1986) 147–153.

    Article  Google Scholar 

  52. Labie, D., Dunda-Belkhodja, O., Rouabhi, F., Pagnier, J., Ragusa, A., and Nagel, R. L., The −158 site 5′ to theGγ gene andGγ expression. Blood66 (1985) 1463–1465.

    PubMed  Google Scholar 

  53. Labie, D., and Nagel, R. L., Genetic heterogeneity of sickle mutations. Acta haemat.78 (1987) 184–185.

    PubMed  Google Scholar 

  54. Lanclos, K. D., Öner, C., Dimovski, A. J., Gu, Y-C., and Huisman, T. H. J., Sequence variations in the 5′ flanking and IVS-II regions of theGγ- andAγ genes of βs chromosomes with five different haplotypes. Blood77 (1991) 2488–2496.

    PubMed  Google Scholar 

  55. Liebhaber, S. A., α-Thalassemia. Hemoglobin13 (1989) 685–731.

    PubMed  Google Scholar 

  56. Liu, D. P., Moi, P., Liu, W., Chang, J., Kan, Y. W., and Curtin, P. T., An erythroid specific enhancer requires a repeated AP-1 motif and other sequence elements for full activity in transgenic mice. Blood76 (1990) 68a (Suppl. 1).

    Google Scholar 

  57. McCurdy, P. R., and Sherman, A. S., Irreversibly sickled cells and red cell survival in sickle cell anemia. Am. J. Med.64 (1978) 253–258.

    Article  PubMed  Google Scholar 

  58. Miller, B. A., Olivieri, N., Salameh, M., Ahmed, M., Antognetti, G., Huisman, T. H. J., Nathan, D. G., and Orkin, S. H., Molecular analysis of the high-Hemoglobin F phenotype in Saudi Arabian sickle cell anemia. N. Engl. J. Med.316 (1987) 244–250.

    PubMed  Google Scholar 

  59. Miller, B. A., Salameh, M., Ahmed, M., Olivieri, N., Huisman, T. H. J., Orkin, S. H., and Nathan, D. G., Saudi Arabian sickle cell anemia-A molecular approach. Ann. N. Y. Acad. Sci.565 (1989) 143–151.

    PubMed  Google Scholar 

  60. Morris, J., Dunn, D., Beckford, M., Grandison, Y., Mason, K., Higgs, D. R., De Ceulear, K., Serjeant, B. E., and Serjeant, G. R., The haematology of homozygous sickle cell disease after the age of 60 years. Br. J. Haemat.77 (1991) 382–385.

    Google Scholar 

  61. Nagel, R. L., Bookchin, R. M., Johnson, J., Labie, D., Isaac-Sodeye, W. A., Honig, G. R., Schiliro, G., Crookston, J. H., and Matsutomo, K., Structural bases of the inhibitory effects of Hemoglobin F and Hemoglobin A2 on the polymerization of Hemoglobin S. Proc. natl Acad. Sci. USA76 (1979) 670–672.

    PubMed  Google Scholar 

  62. Nagel, R. L. and Labie, D., DNA haplotypes and the βs gene, in: Progress in Clinical and Biological Research, Hemoglobin Switching, Part B: Cellular and Molecular Mechanisms, pp. 371–393. Eds G. Stamatoyannopoulos and A. W. Nienhuis. Alan R. Liss, Inc., New York 1989.

    Google Scholar 

  63. Nagel, R. L., and Ranney, D., Genetic epidemiology of structural mutations of the β-globin gene. Semin. Hemat.27 (1990) 332–359.

    Google Scholar 

  64. Nagel, R. L., Rao, S. K., Dunda-Belkodja, O., Connolly, M. M., Fabry, M. E., Georges, A., Krishnamoorthy, R., and Labie, D., The hematological characteristics of sickle cell anemia bearing the Bantu haplotype: The relationship betweenGγ and Hemoglobin F levels. Blood69 (1987) 1026–1030.

    PubMed  Google Scholar 

  65. Ney, P. A., Sorrentino, B. P., McDonagh, K. T., and Nienhuis, A. W., Tandem AP-1 binding sites within the human β-globin dominant control region function as an inducible enhancer in erythroid cells. Gene Develop.4 (1990) 993–1006.

    Google Scholar 

  66. Noguchi, C. T., Dover, G. J., Rodgers, G. P., Serjeant, G. R., Antonarakis, S. E., Anagnou, N. P., Higgs, D. R., Weatherall, D. J., and Schechter, A. N., α-Thalassemia changes erythrocyte heterogeneity in sickle cell disease. J. clin. Invest.75 (1985) 1632–1637.

    PubMed  Google Scholar 

  67. Odenheimer, D. J., Sarnaik, S., Whitten, C. F., Rucknagel, D. L., and Sing, C. P., The relationship between fetal hemoglobin and disease severity in children with sickle cell anemia. Am. J. med. Genet.27 (1987) 525–535.

    Article  PubMed  Google Scholar 

  68. Ojwang, P. J., Ogada, T., Beris, Ph. D., Hattori, Y., Lanclos, K. D., Kutlar, A., Kutlar, F., and Huisman, T. H. J., Haplotypes and α globin gene analyses in sickle cell anemia patients from Kenyn. Br. J. Haemat.65 (1987) 211–216.

    Google Scholar 

  69. Öner, C., Dimovski, A. J., Altay, Ç., Gurgey, A., Gu, Y. C., Huisman, T. H. J., and Lanclos, K. D., Sequence variations in the 5′ hypersensitive site-2 of the locus control region of βs chromosomes are associated with different levels of fetal globin in Hb S homozygotes. Blood79 (1992) 813–819.

    PubMed  Google Scholar 

  70. Öner, C., Dimovski, A. J., Olivieri, N. F., Schiliro, G., Codrington, J. F., Fattoum, S., Adekile, A. D., Öner, R., Yuregir, G. T., Altay, Ç., Gurgey, A., Gupta, R. B., Jogessar, V. B., Kitundu, M. N., Loukopoulos, D., Tamagnini, G. P., Ribeiro, M. L. S., Kutlar, F., Gu, L-H., Lanclos, K. D., and Huisman, T. H. J., βs Haplotypes in various world populations. Hum. Genet.89 (1992) 99–104.

    Article  PubMed  Google Scholar 

  71. Orringer, E. P., Blythe, D. S., Johnson, A. E., Philips, G. Jr, Dover, G. J., and Parker, J. C., Effects of hydroxyurea on Hb F production and water content in the red blood cells of dogs and of patients with sickle cell anemia. Blood78 (1991) 212–216.

    PubMed  Google Scholar 

  72. Philipsen, S., Talbot, D., Fraser, P., and Grosveld, F., The β-globin dominant control region: Hypersensitive site 2. EMBO J.9 (1990) 2159–2167.

    PubMed  Google Scholar 

  73. Platt, O. S., Orkin, S. H., Dover, G. J., Beardsley, G. P., Miller, B. A., and Nathan, D. G., Hydroxyurea enhances fetal hemoglobin production in sickle cell patients. J. clin. Invest.74 (1984) 652–656.

    PubMed  Google Scholar 

  74. Powars, D. R., Chan, L. S., and Schroeder, W. A., The influence of fetal hemoglobin on the clinical expression of sickle cell anemia. Ann. N. Y. Acad. Sci.565 (1989) 262–278.

    PubMed  Google Scholar 

  75. Powars, D. R., Weiss, J. N., Chan, L. S., and Schroeder, W. A., Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia? Blood63 (1984) 921–926.

    PubMed  Google Scholar 

  76. Radice, G., and Constantini, F., Tisse-specific DNase I hypersensitivity sites on a foreign globin gene in transgenic mice. Nucleic Acids Res.14 (1986) 9765–9780.

    PubMed  Google Scholar 

  77. Ragusa, A., Lombardo, M., Bouhassira, E., Beldjord, C., Lombardo, T., Nagel, R. L., Labie, D., and Krishnamoorthy, R., Nucleotide variations in the 3′Aγ enhancer region are linked to β-gene cluster haplotypes and are unrelated to fetal hemoglobin expression. Am. J. hum. Genet.45 (1989) 106–111.

    PubMed  Google Scholar 

  78. Ricco, G., Mazza, U., Turi, R. M., Pich, P. G., Camaschella, C., Saglio, G., and Bernini, L. F., Significance of a new type of human fetal hemoglobin carrying a replacement isoleucine → threonine at position 75 (E19) of the γ chain. Hum. Genet.32 (1976) 305–313.

    Article  PubMed  Google Scholar 

  79. Rucknagel, D. L., Sarnaik, S. A., Whitten, C. F., and Odenheimer, D. A., Fetal hemoglobin concentration predicts disease severity in children with sickle cell anemia, in: Progress in Clinical and Biological Research, Developmental Control of Globin Gene Expression, pp. 487–496. Eds G. Stamatoyannopoulos and A. W. Nienhuis. Alan R. Liss, Inc. New York 1987.

    Google Scholar 

  80. Ryan, T. M., Behringer, R. R., Martin, N. C., Townes, T. M., Palmiter, R. D., and Brinster, R. L., A single erythroid specific DNase I super-sensitive site activates high levels of human β-globin expression in transgenic mice. Gene Develop.3 (1989) 314–323.

    Google Scholar 

  81. Schroeder, W. A., and Huisman, T. H. J., The Chromatography of Hemoglobin, vol. 9, Clinical and Biochemical Analysis. Marcel Dekker, Inc., New York 1980.

    Google Scholar 

  82. Schroeder, W. A., Huisman, T. H. J., Brown, A. K., Uy, R., Bouver, N. G., Lerch, P. O., Shelton, J. R., Shelton, J. B., and Apell, G., Postnatal changes in the chemical heterogeneity of human fetal hemoglobin. Pediatr. Res.5 (1971) 493–499.

    Google Scholar 

  83. Schroeder, W. A., Huisman, T. H. J., Shelton, J. R., Shelton, J. B., Kleihauer, E. F., Dozy, A. M., and Robberson, B., Evidence for multiple structural genes for the γ chain of human fetal hemoglobin. Proc. natl Acad. Sci. USA60 (1968) 537–544.

    PubMed  Google Scholar 

  84. Schroeder, W. A., and Munger, E. S., Sickle cell anaemia, genetic variations, and the slave trade to the United States. J. Afr. Hist.31 (1990) 163–180.

    Google Scholar 

  85. Serjeant, G. R., Fetal hemoglobin in homozygous sickle cell disease. Clin. Hemat.4 (1975) 109–122.

    Google Scholar 

  86. Serjeant, G. R., Serjeant, B. E., Desai, P., Mason, K. P., Sewell, A., and England, J. M., The determinants of irreversibly sickled cells in homozygous sickle cell disease. Br. J. Haemat.40 (1978) 431–438.

    Google Scholar 

  87. Shelton, J. B., Shelton, J. R., and Schroeder, W. A., High performance liquid chromatographic separation of globin chains on a large-pore C4 column. J. liq. Chromat.7 (1984) 1969–1977.

    Google Scholar 

  88. Sorrentino, B., Ney, P., Bodine, D., and Nienhuis, A. W., A 46 base pair enhancer sequence within the locus activation region is required for induced expression of the γ-globin gene during erythroid differentiation. Nucleic Acids Res.18 (1990) 2721–2731.

    PubMed  Google Scholar 

  89. Stamatoyannopoulos, G., Human hemoglobin switching. Science259 (1991) 383.

    Google Scholar 

  90. Stamatoyannopoulos, G., and Nienhuis, A. W., Hemoglobin switching, in: Molecular Basis of Blood Diseases, pp. 66–105, Eds G. Stamatovannopoulos, P. Lederer, P. W. Majerus and A. W. Nienhuis, W. B. Saunders Company. Philadelphia 1987.

    Google Scholar 

  91. Stevens, M. C., Hayes, R. J., Vaidaya, S., and Serjeant, G. R., Fetal hemoglobin and clinical severity of homozygous sickle cell disease in early childhood. J. Pediatr.98 (1981) 37–41.

    PubMed  Google Scholar 

  92. Sunshine, H. R., Hofrichter, J., and Eaton, W. A., Gelation of sickle cell hemoglobin in mixtures with normal adult and fetal hemoglobins. J. molec. Biol.133 (1979) 435–467

    Article  PubMed  Google Scholar 

  93. Talbot, D., Phillpsen, S., Fraser, P., and Grosveld, F., Detailed analysis of the site 3 region of the human β-globin dominant control region. EMBO J.9 (1990) 2169–2177.

    PubMed  Google Scholar 

  94. Tuan, D., Solomon, W., Li, Q., and London, I. M., The “β-like-globin” gene domain in human erythroid cells. Proc. natl Acad. Sci. USA82 (1985) 6384–6388.

    PubMed  Google Scholar 

  95. Tuan, D. Y. H., Solomon, W.B., London, I. M., and Lee D. P., An erythroid-specific, developmental-stage-dependent enhancer far upstream of the human “β-like globin” genes. Proc. natl Acad. Sci. USA86 (1989) 2554–2558.

    PubMed  Google Scholar 

  96. Wrightstone, R. N., and Huisman, T. H. J., On the levels of Hemoglobins F and A2 in sickle cell anemia and some related disorders. Am. J. clin. Path.61 (1974) 375–381.

    PubMed  Google Scholar 

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Adekile, A.D., Huisman, T.H.J. Hb F in sickle cell anemia. Experientia 49, 16–27 (1993). https://doi.org/10.1007/BF01928784

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