Globin Genes: Polymorphic Variants and Mutations

John Michael Old, Oxford Haemophilia Centre, The Churchill Hospital, Oxford, UK

Published online: January 2006

DOI: 10.1038/npg.els.0006078

The globin genes encode the globin chains that make up hemoglobin (Hb). More than 1000 polymorphic variants of the globin genes have been characterized, consisting of single nucleotide substitutions through to complex gene rearrangements. Most globin gene mutations either alter the amino acid sequence of a globin chain, creating an abnormal hemoglobin such as Hb S, or cause a reduction in the synthesis of one or more normal globin chains (the thalassemia disorders). A few mutations cause both types of defect, while others are simple natural polymorphisms that are used as DNA markers.

Keywords: abnormal hemoglobins; thalassemia disorders; globin gene polymorphisms; globin gene mutations; hemoglobin variants; thalassemia mutations

 References
    Antonarakis SE, Boehm CD, Giardeina PJC and Kazazian HH (1982) Non-random association of polymorphic restriction sites in the -globin gene cluster. Proceedings of the National Academy of Sciences of the United States of America 79: 137–141.
    book Bunn HF (2001) "Human hemoglobins: sickle hemoglobin and other mutants". In: Stamatanoyanopoulos G, Majerus PW, Perimutter RM and Varmus H (eds.) The Molecular Basis of Blood Diseases, 3rd edn, pp. 227–274. Philadelphia, PA: WB Saunders
    book Flint J, Harding RM, Boyce AJ and Clegg JB (1998) "The population genetics of the haemoglobinopathies". In: Rogers GP (ed.) Sickle Cell Disease and Thalassaemia, pp. 1–52. London, UK: Baillière Tindall
    Fucharoen S and Winchagoon P (1997) Hemoglobinopathies in Southeast Asia: molecular biology and clinical medicine. Hemoglobin 21: 299–319.
    Hardison RC, Chui DHK, Giardine B, et al. (2002) Hb Var: a relational database of human hemoglobin variants and thalassaemia mutations at the globin gene server. Human Mutation 19: 225–233.
    book Higgs DR (1993) "-Thalassaemia". In: Higgs DR and Weatherall DJ (eds.) The Haemoglobinopathies, pp. 117–150. London, UK: Baillière Tindall
    book Huisman TJH, Carver MFH and Baysal E (1997) A Syallabus of Thalassemia Muations. Augusta, GA: The Sickle Cell Anemia Foundation.
    book Huisman TJH, Carver MFH and Efremov GD (1998) A Syallabus of Human Hemoglobin Variants, 2nd edn. Augusta, GA: The Sickle Cell Anemia Foundation.
    book Stamatanoyanopoulos G and Grosveld F (2001) "Hemoglobin switching". In: Stamatanoyanopoulos G, Majerus PW, Perimutter RM and Varmus H (eds.) The Molecular Basis of Blood Diseases, 3rd edn, pp. 135–182. Philadelphia, PA: WB Saunders
    book Weatherall DJ and Clegg JB (2001) The Thalassaemia Syndromes, 4th edn. Oxford, UK: Blackwell Science.
 Further Reading
    book Bernini LF and Hartevald CL (1998) "-Thalassaemia". Rogers GP (ed.) Sickle Cell Disease and Thalassaemia, pp. 53–90. London, UK: Baillière Tindall
    book Forget BG (2001) "Molecular genetics of the human globin genes". In: Steinberg MH, Forget BG, Higgs DR and Nagel RL (eds.) Disorders of Haemoglobin, pp. 117–130. Cambridge, UK: Cambridge University Press
    book Huisman TJH (1993) "The structure and function of normal and abnormal haemoglobins". In: Higgs DR and Weatherall DJ (eds.) The Haemoglobinopathies, pp. 1–30. London, UK: Baillière Tindall
    book Old J (2002) "Hemoglobinopathies and thalassemias". In: Rimoin DL, Conner JM, Pyeritz RE and Korf BR (eds.) Emery and Rimoin's Principles and Practice of Medical Genetics, 4th ed., pp. 1861–1898. London, UK: Churchill Livingstone
    book Steinberg MH and Nagel RL (2001) "Native and recombinat mutant hemoglobins of biological interest". In: Steinberg MH, Forget BG, Higgs DR and Nagel RL (eds.) Disorders of Haemoglobin, pp. 1195–2014. Cambridge, UK: Cambridge University Press
    book Thein SL (1998) "-Thalassaemia". Rogers GP (ed.) Sickle Cell Disease and Thalassaemia, pp. 53–90. London, UK: Baillière Tindall
    book Thein SL (2001) "Structural variants with a thalassaemia phenotype". In: Steinberg MH, Forget BG, Higgs DR and Nagel RL (eds.) Disorders of Haemoglobin, pp. 342–355. Cambridge, UK: Cambridge University Press
    book Weatherall DJ, Clegg JB, Higgs DR and Wood WG (1995) "The hemoglobinopathies". In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds.) The Metabolic Basis of Disease, 7th ed., pp. 3417–3484. New York, NY: McGraw-Hill
 Web Links
    ePath The Globin Gene Server. A regularly updated database of globin gene mutations http://globin.cse.psu.edu

Related Sub-Topics:

Protein Structure | Transcription | Molecular Genetics of Common and Complex Disease | Specific Genetic Disorders | Proteomic Studies of Genetic Disease | Proteins: Structure, Function, Metabolism | Other Biomolecules: Structure, Function, Metabolism
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Globin Genes: Polymorphic Variants and Mutations
 
How to Cite close
Old, John Michael(Jan 2006) Globin Genes: Polymorphic Variants and Mutations. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006078]