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High frequencies of α-thalassaemia are the result of natural selection by malaria

Nature volume 321, pages 744–750 (1986)Cite this article

Abstract

The frequency of α+-thalassaemia, but not other unlinked DNA polymorphisms, exhibits an altitude- and latitude-dependent correlation with malaria endemicity throughout Melanesia, supporting the hypothesis that protection against this parasitic disease is the major factor responsible for the high frequencies of haemoglobinopathies in many parts of the world.

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References

  1. Haldane, J. B. S. Proc. 8th int. Congr. Genet. 267–273 (Hereditas Suppl. 35, 1949).

  2. Allison, A. C. Br. med. J. 1, 290–294 (1954).

    Article  CAS  Google Scholar 

  3. Allison, A. C. Trans. R. Soc. trop. Med. Hyg. 48, 312–318 (1954).

    Article  CAS  Google Scholar 

  4. Pasvol, G., Weatherall, D. J. & Wilson, R. J. M. Nature 274, 701–703 (1978).

    Article  ADS  CAS  Google Scholar 

  5. Friedman, M. J. Proc. natn. Acad. Sci. U.S.A. 75, 1994–1997 (1978).

    Article  ADS  CAS  Google Scholar 

  6. Livingstone, F. B. in Distribution and Evolution of the Hemoglobin and Globin Loci (ed. Bowman, J. E.) 15–44 (Elsevier, New York, 1983).

    Google Scholar 

  7. Livingstone, F. B. Frequencies of Hemoglobin Variants (Oxford University Press, 1985).

    Google Scholar 

  8. Higgs, D. R. & Weatherall, D. J. Curr. Topics Haemat. 4, 37–97 (1983).

    CAS  Google Scholar 

  9. Higgs, D. R. et al. Br. J. Haemat. 46, 39–46 (1982).

    Article  Google Scholar 

  10. Old, J. M. & Higgs, D. R. in The Thalassaemias (ed. Weatherall, D. J.) 74–102 (Churchill-Livingstone, London, 1983).

    Google Scholar 

  11. Black, R. H. South Pacif. Commn tech. Pap. 81 (South Pacific Commission, Noumea, 1955).

  12. Ewers, W. H. & Jeffrey, W. T. Parasites of Man in Niugini (Jacardanda Press, Milton, 1971).

    Google Scholar 

  13. Bowden, D. K., Hill, A. V. S., Higgs, D. R., Weatherall, D. J. & Clegg, J. B. Lancet ii, 1025–1028 (1985).

    Article  Google Scholar 

  14. Willis, C. & Londo, D. R. Am. J. hum. Genet. 33, 215–226 (1981).

    Google Scholar 

  15. Parkinson, A. D. Papua New Guin. med. J. 17, 8–16 (1973).

    Google Scholar 

  16. Ratard, R. C. Trop. Doctor 9, 212–216 (1979).

    Article  CAS  Google Scholar 

  17. Buxton, P. A. Trans. R. Soc. trop. Med. Hyg. 19, 420–454 (1926).

    Article  Google Scholar 

  18. Buxton, P. A. & Hopkins, G. H. Researches in Polynesia and Melanesia I-IV, 225–230 (London School of Hygiene and Tropical Medicine, 1927).

    Google Scholar 

  19. Tully, W. J. Rep. of Finding by Health Campaign Conducted in the New Hebrides from 31 January 1929 to 21 August 1931 (copy in Library, School of Public Health and Tropical Medicine, Sydney, 1931).

    Google Scholar 

  20. Herivaux, A. Annls Méd. Pharm. colon. 37, 40–62 (1946).

    Google Scholar 

  21. Mauze, J. med. Trop. 6, 109–138 (1946).

    Google Scholar 

  22. Levine, N. D. & Harper, P. Am. J. trop. Med. (Suppl.) 27, 119–128 (1947).

    Article  Google Scholar 

  23. Harper, P., Levine, N. & Liebour, A. Proc. 7th Pacif. Sci. Congr. N.Z. 7, 375–380 (1947).

    Google Scholar 

  24. Lambert, S. M. in Malariology (ed. Boyd, M. F.) 820–830 (W. B. Saunders, Philadelphia, 1949).

    Google Scholar 

  25. Black, R. H. South Pacif. Commn tech. Pap. 60 (South Pacific Commission, Noumea, 1954).

  26. Black, R. H. Aust. Geogr. 6, 32–35 (1955).

    Article  Google Scholar 

  27. Black, R. H. Oceania 27, 136–142 (1956).

    Article  Google Scholar 

  28. Peters, W. Papua New Guin. med. J. 3, 66–75 (1959).

    Google Scholar 

  29. Peters, W. Trans. R. Soc. trop. Med. Hyg. 54, 242–260 (1960).

    Article  CAS  Google Scholar 

  30. Norman-Taylor, W. & Rees, W. H. South Pacif. Commn tech. Pap. 143 (South Pacific Commission, Noumea, 1962).

  31. Van Dijk, W. J. O. M. & Parkinson, A. D. Papua New Guin. med. J. 17, 17–21 (1973).

    Google Scholar 

  32. Embury, S. H. et al. J. clin. Invest. 66, 1319–1325, (1980).

    Article  CAS  Google Scholar 

  33. Higgs, D. R., Hill, A. V. S., Bowden, D. K., Weatherall, D. J. & Clegg, J. B. Nucleic Acids Res. 12, 6965–6977 (1984).

    Article  CAS  Google Scholar 

  34. Hill, A. V. S. et al. Am. J. hum. Genet. 37, 571–580 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Mills, A. R. J. trop. Med. Hyg. 57, 99–107 (1954).

    CAS  PubMed  Google Scholar 

  36. Laird, M. Bull. ent. Res. 45, 279–283 (1954).

    Article  Google Scholar 

  37. Booth, K. Papua New Guin. med. J. 24, 264–266 (1981).

    CAS  Google Scholar 

  38. Oppenheimer, S. J., Higgs, D. R., Weatherall, D. J., Barker, J. & Spark, B. A. Lancet i, 424–426 (1984).

    Article  Google Scholar 

  39. Yenchitsomanus, P.-J., Summers, K. M., Bhatia, K., Cattani, J. & Board, P. G. Am. J. hum. Genet. 37, 778–784 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Siniscalco, M. et al. Bull. Wld Hlth Org. 34, 379–393 (1966).

    CAS  Google Scholar 

  41. Breinl, A. Ann. trop. Med. Parasit. 9, 285–334 (1915).

    Article  Google Scholar 

  42. Peters, W. & Christian, S. H. Trans. R. Soc. trop. Med. Hyg. 54, 529–536 (1960).

    Article  CAS  Google Scholar 

  43. Orkin, S. H. & Kazazian, H. H. A. Rev. Genet. 18, 131–171 (1984).

    Article  CAS  Google Scholar 

  44. Higgs, D. R. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).

  45. Simmons, R. T. & Booth, P. B. A Compendium of Melanesian Genetic Data I-IV (Commonwealth Serum Laboratories, Victoria, 1971).

    Google Scholar 

  46. Hill, A. V. S., Bowden, D. K., Weatherall, D. J. & Clegg, J. B. Blood (in the press).

  47. Povey, S., Morton, N. E. & Sherman, S. L. Cytogenet. Cell Genet. 40, 67–106 (1985).

    Article  CAS  Google Scholar 

  48. Gilliam, T. C. et al. Hum. Genet. 68, 154–158 (1984).

    Article  CAS  Google Scholar 

  49. Davies, K. E. et al. J. med. Genet. 19, 259–263 (1983).

    Article  Google Scholar 

  50. Bell, G. I., Karam, J. H. & Rutter, W. J. Proc. natn. Acad. Sci. U.S.A. 78, 5759–5763 (1981).

    Article  ADS  CAS  Google Scholar 

  51. Capon, D. J., Chen, E. Y., Levinson, A. D., Seeburg, P. H. & Goeddel, D. V. Nature 302, 33–37 (1983).

    Article  ADS  CAS  Google Scholar 

  52. White, R. et al. Nature 313, 101–105 (1985).

    Article  ADS  CAS  Google Scholar 

  53. Smithies, O. & Walker, W. F. Nature 176, 1265–1266 (1955).

    Article  ADS  CAS  Google Scholar 

  54. Sukumaran, P. K. et al. Nucleic Acids Res. 11, 4635–4643 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Trent, R. J. et al. Nucleic Acids Res. 9, 6723–6733 (1981).

    Article  CAS  Google Scholar 

  56. Smouse, P. E. & Ward, R. H. Genetics 88, 611–631 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Imaizumi, Y. & Morton, N. E. Archaeol. phys. Anthrop., Oceania 5, 218–227 (1970).

    Google Scholar 

  58. Giles, E., Wyber, S. & Walsh, R. Archaeol. phys. Anthrop., Oceania 5, 60–72 (1970).

    Google Scholar 

  59. Cavalli-Sforza, L. L. & Bodmer, W. F. The Genetics of Human Populations (W. H. Freeman, San Francisco, 1971).

    Google Scholar 

  60. Littlewood, R. A. J. Polynes. Soc. 75, 95–106 (1966).

    Google Scholar 

  61. Bellwood, P. Man's Conquest of the Pacific (Collins, London, 1978).

    Google Scholar 

  62. Trent, R. J. et al. Am. J. Hemat. 18, 431–433 (1985).

    Article  CAS  Google Scholar 

  63. White, J. P. & O'Connell, J. F. A Prehistory of Australia, New Guinea and Sahul (Academic, Sydney, 1983).

    Google Scholar 

  64. Wurm, S. A., Laycock, D. C., Vorhoeve, C. L. & Dutton, T. E. in New Guinea Area Languages and Language Study Vol. 1 (ed. Wurm, S. A.) 935–960 (Australian National University, Canberra, 1975).

    Google Scholar 

  65. Kirk, R. L. in The First Americans: Origins Affinities and Adaptations (ed. Laughlin, W. S.) 211–237 (Gustav-Fischer, New York, 1979).

    Google Scholar 

  66. Kirk, R. L. in Population Structure and Genetic Disorders (eds Eriksson, A. N., Forsius, H., Nevanlinna, H. R., Workman, P. L. & Noris, P. K.) 113–137 (Academic. London, 1980).

    Google Scholar 

  67. Booth, P. B. & Simmons, R. T. Papua New Guin. med. J. 15, 10–14 (1972).

    Google Scholar 

  68. Blake, N. M. Hum. Genet. 70, 1–12 (1978).

    Google Scholar 

  69. Booth, P. B. & McLoughlin, K. Vox Sang. 22, 73–84 (1972).

    Article  CAS  Google Scholar 

  70. Flint, J., Hill, A. V. S., Clegg, J. B., Weatherall, D. J. & Higgs, D. R. Br. J. Haemat. (in the press).

  71. Pasvol, G. & Wilson, R. J. M. Br. med. Bull. 38, 133–140 (1982).

    Article  CAS  Google Scholar 

  72. Ifediba, T. C., Stern, A., Ibrahim, A. & Rieder, R. F. Blood 65, 452–455 (1985).

    CAS  PubMed  Google Scholar 

  73. Higgs, D. R., Old, J. M., Pressley, L., Clegg, J. B. & Weatherall, D. J. Nature 284, 632–635 (1980).

    Article  ADS  CAS  Google Scholar 

  74. Goossens, M., Dozy, A. N., Embury, S. H. & Kan, Y. W. Proc. natn. Acad. Sci. U.S.A. 77, 518–521 (1980).

    Article  ADS  CAS  Google Scholar 

  75. Trent, R. J., Higgs, D. R., Clegg, J. B. & Weatherall, D. J. Br. J. Haemat. 49, 149–152 (1981).

    Article  CAS  Google Scholar 

  76. Bonnisseau, G. thesis, Univ. René Descartes, Paris (1975).

  77. Manson-Bahr, P. E. C. & Apted, F. I. C. in Tropical Diseases 18th edn, 41 (Bailliere-Tindall, London, 1982).

    Google Scholar 

  78. Hill, A. V. S., Nicholls, R. D., Thein, S. L. & Higgs, D. R. Cell 42, 809–819 (1985).

    Article  CAS  Google Scholar 

  79. Bell, G. I., Horita, S. & Karam, J. H. Diabetes 33, 137–181 (1984).

    Google Scholar 

  80. Goodbourn, S. E. Y., Higgs, D. R., Clegg, J. B. & Weatherall, D. J. Molec. Biol. Med. 2, 223–238 (1984).

    CAS  PubMed  Google Scholar 

  81. Hill, A. V. S. et al. Am. J. hum. Genet. 38, 382–389 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. An Atlas of Papua New Guinea (Department of Geography, University of Papua New Guinea; Collins Longman, Harlow, 1970).

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Authors and Affiliations

  1. MRC Molecular Haematology Unit, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    J. Flint, A. V. S. Hill, D. J. Weatherall & J. B. Clegg

  2. Department of Anatomy, Monash University, Clayton, Victoria, 3168, Australia

    D. K. Bowden

  3. Department of Tropical Paediatrics, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK

    S. J. Oppenheimer

  4. Department of Clinical Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea

    P. R. Sill

  5. Department of Human Biology, John Curtin School of Medical Research, Canberra, ACT, 2601, Australia

    S. W. Serjeantson

  6. Moratona Health Centre, Panguna, North Solomons Province, Papua New Guinea

    J. Bana-Koiri

  7. Papua New Guinea Institute for Medical Research, Goroka, Papua New Guinea

    K. Bhatia & M. P. Alpers

  8. Department of Biological Anthropology, University of Oxford, Oxford, OX1 2JD, UK

    A. J. Boyce

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Flint, J., Hill, A., Bowden, D. et al. High frequencies of α-thalassaemia are the result of natural selection by malaria. Nature 321, 744–750 (1986). https://doi.org/10.1038/321744a0

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