1932

Abstract

Although the inherited hemoglobin disorders were the first genetic diseases to be explored at the molecular level, they still have important messages for the future of medical genetics. In particular, they can offer a better understanding of the evolutionary and population biology of genetic disease, the mechanisms that underlie the phenotypic diversity of monogenic disease, and how, by developing appropriate partnerships, richer countries can help low-income countries to evolve programs for the control and management of these diseases where, in many cases, they are particularly common.

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2013-08-31
2024-06-21
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Literature Cited

  1. Allen A, Fisher C, Premawardena A, Bandara D, Perera A. 1.  et al. 2012. Methemoglobinemia and ascorbate deficiency in hemoglobin E β thalassemia: metabolic and clinical implications. Blood 120:2939–44 [Google Scholar]
  2. Allen A, Fisher C, Premawardena A, Peto T, Allen S. 2.  et al. 2010. Adaptation to anemia in hemoglobin E-β thalassemia. Blood 116:5368–70 [Google Scholar]
  3. Allen SJ, O'Donnell A, Alexander NDE, Alpers MP, Peto TEA. 3.  et al. 1997. α+-Thalassemia protects children against disease caused by other infections as well as malaria. Proc. Natl. Acad. Sci. USA 94:14736–41 [Google Scholar]
  4. Allison AC. 4.  1954. Protection afforded by sickle-cell trait against subtertian malarial infection. Br. Med. J. 1954:4587290–94 [Google Scholar]
  5. Alter BP. 5.  1990. Antenatal diagnosis: summary of results. Ann. N. Y. Acad. Sci. 612:237–50 [Google Scholar]
  6. Alter BP, Modell CB, Fairweather D, Hobbins JC, Mahoney MJ. 6.  et al. 1976. Prenatal diagnosis of hemoglobinopathies: a review of 15 cases. N. Engl. J. Med. 295:1437–43 [Google Scholar]
  7. Angelini V. 7.  1937. Primi risultati di ricerche ematologiche nei familiari di ammalati di anemia di Cooley. Minerva Med. 28:331–32 [Google Scholar]
  8. Antonarakis SE, Boehm CD, Giardina PVJ, Kazazian HH. 8.  1982. Nonrandom association of polymorphic restriction sites in the β-globin gene complex. Proc. Natl. Acad. Sci. USA 79:137–41 [Google Scholar]
  9. Baglioni C. 9.  1962. The fusion of two peptide chains in hemoglobin Lepore and its interpretation as a genetic deletion. Proc. Natl. Acad. Sci. USA 48:1880–86 [Google Scholar]
  10. Bank A, Marks PA. 10.  1966. Excess α chain synthesis relative to β chain synthesis in thalassaemia major and minor. Nature 212:1198–200 [Google Scholar]
  11. Bannerman RM. 11.  1961. Thalassemia: A Survey of Some Aspects. New York: Grune and Stratton [Google Scholar]
  12. Bauer DE, Kamran SC, Orkin SH. 12.  2012. Reawakening fetal hemoglobin: prospects for new therapies for the β-globin disorders. Blood 120:2945–53 [Google Scholar]
  13. Benz EJ, Forget BG. 13.  1971. Defect in messenger RNA for human hemoglobin synthesis in beta thalassemia. J. Clin. Investig. 50:2755–60 [Google Scholar]
  14. Borg J, Patrinos GP, Felice AE, Philipsen S. 14.  2011. Erythroid phenotypes associated with KLF1 mutations. Haematologica 96:635–38 [Google Scholar]
  15. Burka ER, Marks PA. 15.  1963. Ribosomes active in protein synthesis in human reticulocytes: a defect in thalassaemia major. Nature 199:706–7 [Google Scholar]
  16. Caminopetros J. 16.  1938. Recherches sur l'anémia érythroblastique infantile des peuples de la Mediterranée orientale. Etude anthropologique, étiologique et pathogénique. La transmission hereditaire de la maladia. Ann. Méd. 43:104–25 [Google Scholar]
  17. Chang H, Modell CB, Alter BP, Dickinson MJ, Frigoletto FD. 17.  et al. 1975. Expression of the β-thalassemia gene in the first trimester fetus. Proc. Natl. Acad. Sci. USA 72:3633–37 [Google Scholar]
  18. Chang JC, Kan YW. 18.  1979. β0 thalassemia, a nonsense mutation in man. Proc. Natl. Acad. Sci. USA 76:2886–89 [Google Scholar]
  19. Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB. 19.  et al. 1995. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N. Engl. J. Med. 332:1317–22 [Google Scholar]
  20. Chini V, Valeri CM. 20.  1949. Mediterranean hemopathic syndromes. Blood 4:989–1013 [Google Scholar]
  21. Clegg JB, Weatherall DJ. 21.  1967. Haemoglobin synthesis in α-thalassaemia (haemoglobin H disease). Nature 215:1241–43 [Google Scholar]
  22. Clegg JB, Weatherall DJ, Milner PF. 22.  1971. Haemoglobin Constant Spring—a chain termination mutant?. Nature 234:337–40 [Google Scholar]
  23. Clegg JB, Weatherall DJ, Na-Nakorn S, Wasi P. 23.  1968. Haemoglobin synthesis in β-thalassaemia. Nature 220:664–68 [Google Scholar]
  24. Colah R, Gorakshakar A, Phanasgaonkar S, D'Souza E, Nadkarni A. 24.  et al. 2010. Epidemiology of β-thalassaemia in Western India: mapping the frequencies and mutations in sub-regions of Maharashtra and Gujarat. Br. J. Haematol. 149:739–47 [Google Scholar]
  25. Cooley TB, Lee P. 25.  1925. A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans. Am. Pediatr. Soc. 37:29 [Google Scholar]
  26. de Silva S, Fisher CA, Premawardhena A, Lamabadusuriya SP, Peto TE. 26.  et al. 2000. Thalassaemia in Sri Lanka: implications for the future health burden of Asian populations. Lancet 355:786–91 [Google Scholar]
  27. Dintzis HM. 27.  1961. Assembly of the peptide chains of hemoglobin. Proc. Natl. Acad. Sci. USA 47:247–50 [Google Scholar]
  28. Eaton WA. 28.  2003. Linus Pauling and sickle cell disease. Biophys. Chem. 100:109–16 [Google Scholar]
  29. Embury SH, Lebo RV, Dozy AM, Kan YW. 29.  1979. Organization of the α-globin genes in the Chinese α-thalassemia syndromes. J. Clin. Investig. 63:1307–10 [Google Scholar]
  30. Embury SH, Miller JA, Dozy AM, Kan YW, Chan V, Todd D. 30.  1980. Two different molecular organizations account for the single α-globin gene of the α-thalassemia-2 genotype. J. Clin. Investig. 66:1319–25 [Google Scholar]
  31. Fisher CA, Premawardhena A, de Silva S, Perera G, Rajapaksa S. 31.  et al. 2003. The molecular basis for the thalassaemias in Sri Lanka. Br. J. Haematol. 121:662–71 [Google Scholar]
  32. Forget BG, Baltimore D, Benz EJ, Housman D, Lebowitz P. 32.  et al. 1974. Globin messenger RNA in the thalassemia syndromes. Ann. N. Y. Acad. Sci. 232:76–87 [Google Scholar]
  33. Fucharoen S, Weatherall DJ. 33.  2012. The hemoglobin E thalassemias. Cold Spring Harb. Perspect. Med. 2:a011734 [Google Scholar]
  34. Galarneau G, Palmer CD, Sankaran VG, Orkin SH, Hirschhorn JN, Lettre G. 34.  2010. Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation. Nat. Genet. 42:1049–51 [Google Scholar]
  35. Garrod AE. 35.  1909. Inborn Errors of Metabolism: The Croonian Lectures Delivered Before the Royal College of Physicians in London, in June, 1908. London: Henry Frowde and Hodder & Stoughton [Google Scholar]
  36. Gerald PS, Diamond LK. 36.  1958. The diagnosis of thalassemia trait by starch block electrophoresis of the hemoglobin. Blood 13:61–69 [Google Scholar]
  37. Gibbons RJ. 37.  2012. α-Thalassemia, mental retardation, and myelodysplastic syndrome. Cold Spring Harb. Perspect. Med. 2:a011759 [Google Scholar]
  38. Gouagna LC, Bancone G, Yao F, Yameogo B, Dabire KR. 38.  et al. 2010. Genetic variation in human HBB is associated with Plasmodium falciparum transmission. Nat. Genet. 42:328–31 [Google Scholar]
  39. Haldane JBS. 39.  1949. The rate of mutation of human genes. Hereditas 35:Suppl.267–73 [Google Scholar]
  40. Haverfield EV, McKenzie CA, Forrester T, Bouzekri N, Harding R. 40.  et al. 2005. UGT1A1 variation and gallstone formation in sickle cell disease. Blood 105:968–72 [Google Scholar]
  41. Hebbel RP, Schechter AN, Elion J. 41.  2013. Pathophysiology of sickle cell disease. Cold Spring Harb. Perspect. Med. In press [Google Scholar]
  42. Herrick JB. 42.  1910. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch. Intern. Med. 6:517–21 [Google Scholar]
  43. Heywood JD, Karon M, Weissman S. 43.  1964. Amino acids: incorporation into α- and β-chains of hemoglobin by normal and thalassemic reticulocytes. Science 146:530–31 [Google Scholar]
  44. Higgs DR. 44.  2013. The molecular basis of α-thalassemia. Cold Spring Harb. Perspect. Med. 3:a011718 [Google Scholar]
  45. Hollan SR, Szelenyi JG, Brimhall G, Duerst M, Jones RT. 45.  et al. 1972. Multiple alpha chain loci for human haemoglobins: Hb J-Buda and Hb G-Pest. Nature 235:47–50 [Google Scholar]
  46. Houle D, Govindaraju DR, Omholt S. 46.  2010. Phenomics: the next challenge. Nat. Rev. Genet. 11:855–66 [Google Scholar]
  47. Housman D, Forget BG, Skoultchi A, Benz EJ. 47.  1973. Quantitative deficiency of chain specific messenger ribonucleic acids in the thalassemia syndromes. Proc. Natl. Acad. Sci. USA 70:1809–13 [Google Scholar]
  48. Hunt JA, Lehmann H. 48.  1959. Abnormal human haemoglobins: haemoglobin “Bart's”: a foetal haemoglobin without α chains. Nature 184:872–73 [Google Scholar]
  49. Ingram VM. 49.  1956. Specific chemical difference between the globins of normal human and sickle-cell anaemia haemoglobin. Nature 178:792–94 [Google Scholar]
  50. Ingram VM, Stretton AOW. 50.  1959. Genetic basis of the thalassemia diseases. Nature 184:1903–9 [Google Scholar]
  51. Jones RT, Schroeder WA. 51.  1963. Chemical characterization and subunit hybridization of human hemoglobin H and associated compounds. Biochemistry 2:1357–67 [Google Scholar]
  52. Kan YW, Dozy AM. 52.  1978. Polymorphisms of DNA sequence adjacent to human β-globin structural gene: relationship to sickle mutation. Proc. Natl. Acad. Sci. USA 75:5631–35 [Google Scholar]
  53. Kunkel HG, Ceppellini R, Müller-Eberhard U, Wolf J. 53.  1957. Observations on the minor basic hemoglobin component in blood of normal individuals and patients with thalassemia. J. Clin. Investig. 36:1615–25 [Google Scholar]
  54. Lambotte-Legrand J, Lambotte-Legrand C. 54.  1951. L'anémie à hématies falciformes chez l'enfant indigène du Bas-Congo. Ann. Soc. Belge Méd. Trop. 31:207–34 [Google Scholar]
  55. Lettre G. 55.  2012. The search for genetic modifiers of disease severity in the β-hemoglobinopathies. Cold Spring Harb. Perspect. Med. 2:a015032 [Google Scholar]
  56. Lucarelli G, Giardini C, Baronciani D. 56.  1995. Bone marrow transplantation in β-thalassemia. Semin. Hematol. 32:297–303 [Google Scholar]
  57. Menard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR. 57.  et al. 2010. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc. Natl. Acad. Sci. USA 107:5967–71 [Google Scholar]
  58. Miller LH, Mason SJ, Clyde DF, McGinniss MH. 58.  1976. The resistance factor to Plasmodium vivax in blacks. N. Engl. J. Med. 295:302–4 [Google Scholar]
  59. Neel JV. 59.  1949. Inheritance of sickle-cell anemia. Science 110:64–66 [Google Scholar]
  60. Neel JV. 60.  1962. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”?. Am. J. Hum. Genet. 14:353–62 [Google Scholar]
  61. Nienhuis AW, Anderson WF. 61.  1971. Isolation and translation of hemoglobin messenger RNA from thalassemia, sickle cell anemia, and normal human reticulocytes. J. Clin. Investig. 50:2458–62 [Google Scholar]
  62. Nienhuis AW, Nathan DG. 62.  2012. Pathophysiology and clinical manifestations of the β-thalassemias. Cold Spring Harb. Perspect. Med. 2:a011726 [Google Scholar]
  63. Nienhuis AW, Persons DA. 63.  2012. Development of gene therapy for thalassemia. Cold Spring Harb. Perspect. Med. 2:a011833 [Google Scholar]
  64. O'Donnell A, Premawardhena A, Arambepola M, Allen SJ, Peto TE. 64.  et al. 2007. Age-related changes in adaptation to severe anemia in childhood in developing countries. Proc. Natl. Acad. Sci. USA 104:9440–44 [Google Scholar]
  65. O'Donnell A, Premawardhena A, Arambepola M, Samaranayake R, Allen SJ. 65.  et al. 2009. Interaction of malaria with a common form of severe thalassemia in an Asian population. Proc. Natl. Acad. Sci. USA 106:18716–21 [Google Scholar]
  66. Ohta Y, Yamaoka K, Sumida I, Yanase T. 66.  1971. Haemoglobin Miyada, a β–δ fusion peptide (anti-Lepore) type discovered in a Japanese family. Nat. New Biol. 234:218–20 [Google Scholar]
  67. Old JM, Fitches A, Heath C, Thein SL, Weatherall DJ. 67.  et al. 1986. First-trimester fetal diagnosis for haemoglobinopathy: report on 200 cases. Lancet 328:763–67 [Google Scholar]
  68. Old JM, Proudfoot NJ, Wood WG, Longley JI, Clegg JB, Weatherall DJ. 68.  1978. Characterization of β-globin mRNA in the β0 thalassemias. Cell 14:289–98 [Google Scholar]
  69. Old JM, Ward RHT, Petrou M, Karagozlu F, Modell B, Weatherall DJ. 69.  1982. First-trimester fetal diagnosis for haemoglobinopathies: three cases. Lancet 320:1413–16 [Google Scholar]
  70. Olivieri NF, Muraca GM, O'Donnell A, Premawardhena A, Fisher C, Weatherall DJ. 70.  2008. Studies in haemoglobin E beta-thalassaemia. Br. J. Haematol. 141:388–97 [Google Scholar]
  71. Olivieri NF, Weatherall DJ. 71.  2009. Clinical aspects of β thalassemia and related disorders. Disorders of Hemoglobin MH Steinberg, BG Forget, DR Higgs, DJ Weatherall 357–416 Cambridge, UK: Cambridge Univ. Press, 2nd ed.. [Google Scholar]
  72. O'Riordan S, Hien TT, Miles K, Allen A, Quyen NN. 72.  et al. 2010. Large scale screening for haemoglobin disorders in southern Vietnam: implications for avoidance and management. Br. J. Haematol. 150:359–64 [Google Scholar]
  73. Orkin SH, Alter BP, Altay C, Mahoney MJ, Lazarus H. 73.  et al. 1978. Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. N. Engl. J. Med. 299:166–72 [Google Scholar]
  74. Orkin SH, Kazazian HH Jr, Antonarakis SE, Goff SC, Boehm CD. 74.  et al. 1982. Linkage of β-thalassaemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human β-globin gene cluster. Nature 296:627–31 [Google Scholar]
  75. Orkin SH, Kazazian HH Jr, Antonarakis SE, Ostrer H, Goff SC, Sexton JP. 75.  1982. Abnormal RNA processing due to the exon mutation of βE-globin gene. Nature 300:768–69 [Google Scholar]
  76. Orkin SH, Old JM, Lazarus H, Altay C, Gurgey A. 76.  et al. 1979. The molecular basis of α-thalassemias: frequent occurrence of dysfunctional α loci among non-Asians with Hb H disease. Cell 17:33–43 [Google Scholar]
  77. Orkin SH, Old JM, Weatherall DJ, Nathan DG. 77.  1979. Partial deletion of β-globin gene DNA in certain patients with β0-thalassemia. Proc. Natl. Acad. Sci. USA 76:2400–4 [Google Scholar]
  78. Ottolenghi S, Lanyon WG, Paul J, Williamson R, Weatherall DJ. 78.  et al. 1974. The severe form of α thalassaemia is caused by a haemoglobin gene deletion. Nature 251:389–92 [Google Scholar]
  79. Pauling L, Itano HA, Singer SJ, Wells IG. 79.  1949. Sickle cell anemia, a molecular disease. Science 110:543–48 [Google Scholar]
  80. Penman BS, Pybus OG, Weatherall DJ, Gupta S. 80.  2009. Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean. Proc. Natl. Acad. Sci. USA 106:21242–46 [Google Scholar]
  81. Perutz MF, Rossman MG, Cullis AF, Muirhead H, Will G, North ACT. 81.  1960. Structure of haemoglobin. Nature 185:416–22 [Google Scholar]
  82. Polani PE. 82.  1990. The Impact of Genetics on Medicine: The Harveian Oration Delivered at the Royal College of Physicians, 18th October 1988. London: R. Coll. Physicians86 [Google Scholar]
  83. Premawardhena A, Fisher CA, Fathiu F, de Silva S, Perera W. 83.  et al. 2001. Genetic determinants of jaundice and gallstones in haemoglobin E β thalassaemia. Lancet 357:1945–46 [Google Scholar]
  84. Premawardhena A, Fisher CA, Liu YT, Verma IC, de Silva S. 84.  et al. 2003. The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications. Blood Cells Mol. Dis. 31:98–101 [Google Scholar]
  85. Premawardhena A, Fisher CA, Olivieri NF, de Silva S, Arambepola M. 85.  et al. 2005. Haemoglobin E β thalassaemia in Sri Lanka. Lancet 366:1467–70 [Google Scholar]
  86. Ranney HM. 86.  2001. Hemoglobin: a historical perspective. Disorders of Hemoglobin MH Steinberg, BG Forget, DR Higgs, RL Nagel 1–24 Cambridge, UK: Cambridge Univ. Press, 1st ed.. [Google Scholar]
  87. Sankaran VG, Nathan DG. 87.  2010. Reversing the hemoglobin switch. N. Engl. J. Med. 363:2258–60 [Google Scholar]
  88. Seguin B, Hardy BJ, Singer PA, Daar AS. 88.  2008. Genomic medicine and developing countries: creating a room of their own. Nat. Rev. Genet. 9:487–93 [Google Scholar]
  89. Seguin B, Hardy BJ, Singer PA, Daar AS. 89.  2008. Human genomic variation initiatives in emerging economies and developing countries. Nat. Rev. Genet. 9:S3–9 [Google Scholar]
  90. Silvestroni E, Bianco I. 90.  1946. Una nova entita nosologica: la malatia microdrepanocitica. Haematologica 29:453–88 [Google Scholar]
  91. Spritz RA, Jagadeeswaran P, Choudary PV, Biro PA, Elder JT. 91.  et al. 1981. Base substitution in an intervening sequence of a β+ thalassemic human globin gene. Proc. Natl. Acad. Sci. USA 78:2455–59 [Google Scholar]
  92. St Pierre T, Olivieri NF, Thayalasuthan V, Muraca G, Weatherall D. 92.  et al. 2011. Relationship between serum ferritin and liver iron concentration in hemoglobin E thalassemia. Haematologica 96:69 [Google Scholar]
  93. Sturgeon P, Itano HA, Valentine WN. 93.  1952. Chronic hemolytic anemia associated with thalassemia and sickling trait. Blood 7:350–57 [Google Scholar]
  94. Suresh S, Fisher C, Ayyub H, Premawardena A, Allen A. 94.  et al. 2013. Alpha thalassaemia and extended alpha globin genes in Sri Lanka. Blood Cells Mol. Dis. 50:93–98 [Google Scholar]
  95. Taylor JM, Dozy A, Kan YW, Varmus HE, Lie-Injo LE. 95.  et al. 1974. Genetic lesion in homozygous α-thalassaemia (hydrops foetalis). Nature 251:392–93 [Google Scholar]
  96. Vecchio F. 96.  1946. Sulla resistenza della emoglobina alla denaturazione alcalina in alcune sindromi emopatiche. Pediatria 54:545–48 [Google Scholar]
  97. Vichinsky EP. 97.  2013. Clinical manifestations of α-thalassemia. Cold Spring Harb. Perspect. Med. 3:a011742 [Google Scholar]
  98. Wasi P, Na-Nakorn S, Suingdumrong A. 98.  1964. Haemoglobin H disease in Thailand: a genetical study. Nature 204:907–8 [Google Scholar]
  99. Weatherall DJ. 99.  1963. Abnormal haemoglobins in the neonatal period and their relationship to thalassaemia. Br. J. Haematol. 9:265–77 [Google Scholar]
  100. Weatherall DJ. 100.  2001. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat. Rev. Genet. 2:245–55 [Google Scholar]
  101. Weatherall DJ. 101.  2008. Genetic variation and susceptibility to infection: the red cell and malaria. Br. J. Haematol. 141:276–86 [Google Scholar]
  102. Weatherall DJ. 102.  2010. The importance of micromapping the gene frequencies for the common inherited disorders of haemoglobin. Br. J. Haematol. 149:635–37 [Google Scholar]
  103. Weatherall DJ. 103.  2010. The inherited diseases of hemoglobin are an emerging global health burden. Blood 115:4331–36 [Google Scholar]
  104. Weatherall DJ. 104.  2010. Thalassaemia: The Biography. Oxford, UK: Oxford Univ. Press [Google Scholar]
  105. Weatherall DJ. 105.  2010. Thalassemia as a global health problem: recent progress towards its control in the developing countries. Ann. N. Y. Acad. Sci. 1202:17–23 [Google Scholar]
  106. Weatherall DJ. 106.  2011. The challenge of haemoglobinopathies in resource-poor countries. Br. J. Haematol. 154:736–44 [Google Scholar]
  107. Weatherall DJ, Clegg JB. 107.  1969. Disordered globin synthesis in thalassemia. Ann. N. Y. Acad. Sci. 165:242–52 [Google Scholar]
  108. Weatherall DJ, Clegg JB. 108.  1975. The α chain termination mutants and their relationship to thalassaemia. Philos. Trans. R. Soc. Lond. B 271:411–55 [Google Scholar]
  109. Weatherall DJ, Clegg JB. 109.  2001. The Thalassaemia Syndromes Oxford: Blackwell Sci, 4th ed.. [Google Scholar]
  110. Weatherall DJ, Clegg JB, Boon WH. 110.  1970. The haemoglobin constitution of infants with the haemoglobin Bart's hydrops foetalis syndrome. Br. J. Haematol. 18:357–67 [Google Scholar]
  111. Weatherall DJ, Clegg JB, Naughton MA. 111.  1965. Globin synthesis in thalassemia: an in vitro study. Nature 208:1061–65 [Google Scholar]
  112. Weatherall DJ, Higgs DR, Bunch C, Old JM, Hunt DM. 112.  et al. 1981. Hemoglobin H disease and mental retardation—a new syndrome or a remarkable coincidence?. N. Engl. J. Med. 305:607–12 [Google Scholar]
  113. Weatherall DJ, Vella F. 113.  1960. Thalassaemia in a Gurkha family. Br. Med. J. 1960:51871711–13 [Google Scholar]
  114. Westaway D, Williamson R. 114.  1981. An intron nucleotide sequence variant in a cloned β+ thalassaemia globin gene. Nucleic Acids Res. 9:1777–88 [Google Scholar]
  115. Whipple GH, Bradford WL. 115.  1932. Racial or familial anemia of children: associated with fundamental disturbances of bone and pigment metabolism (Cooley-Von Jaksch). Am. J. Dis. Child. 44:336–65 [Google Scholar]
  116. Williams TN, Maitland K, Bennett S, Ganczakowski M, Peto TEA. 116.  et al. 1996. High incidence of malaria in α-thalassaemic children. Nature 383:522–25 [Google Scholar]
  117. Williams TN, Mwangi TW, Wambua S, Peto TE, Weatherall DJ. 117.  et al. 2005. Negative epistasis between the malaria-protective effects of α+-thalassemia and the sickle cell trait. Nat. Genet. 37:1253–57 [Google Scholar]
  118. Williams TN, Uyoga S, Macharia A, Ndila C, McAuley CF. 118.  et al. 2009. Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case-control study. Lancet 374:1364–70 [Google Scholar]
  119. Williams TN, Weatherall DJ. 119.  2012. World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb. Perspect. Med. 2:a011692 [Google Scholar]
  120. 120. World Health Organ 2002. Genomics and World Health Geneva: World Health Organ. [Google Scholar]
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