Human Genetics

, Volume 115, Issue 4, pp 269–279 | Cite as

The origin and spread of the HFE-C282Y haemochromatosis mutation

  • S. Distante
  • K. J. H. Robson
  • J. Graham-Campbell
  • A. Arnaiz-Villena
  • P. Brissot
  • Mark WorwoodEmail author
Review Article


The mutation responsible for most cases of genetic haemochromatosis in Europe (HFE C282Y) appears to have been originated as a unique event on a chromosome carrying HLA-A3 and -B7. It is often described as a “Celtic mutation”—originating in a Celtic population in central Europe and spreading west and north by population movement. It has also been suggested that Viking migrations were largely responsible for the distribution of this mutation. Two, initial estimates of the age of the mutation are compatible with either of these suggestions. Here we examine the evidence about HFE C282Y frequencies, extended haplotypes involving HLA-A and -B alleles, the validity of calculations of mutation age, selective advantage and current views on the relative importance of “demic-diffusion” (population migration) and “adoption-diffusion” (cultural change) in the neolithic transition in Europe and since then. We conclude that the HFE C282Y mutation occurred in mainland Europe before 4,000 BC.


Cystic Fibrosis Population Movement C282Y Mutation Ancestral Haplotype Neolithic Transition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This paper resulted from a meeting on “The Origin and Spread of the Haemochromatosis Mutation” held at the Moller Centre, Cambridge, 31 January–1 February 2003. The participants were: Antonio Arnaiz-Villena, Universidad Complutense, Madrid; Berit Borch-Iohnsen, School of Medicine, University of Oslo; Pierre Brissot, Faculté de Médecine, Rennes; Tim Cox, University of Cambridge; Sonia Distante, Aker University Hospital; James Graham-Campbell, University College London; Carmen Lanzara, Second University of Naples; Gérard Lucotte, Centre de Génétique Moléculaire, Paris; Alison Merryweather-Clarke, Weatherall Institute of Molecular Medicine, Oxford; Nils Milmann, Department of Medicine, Naestved Hospital; Jennifer Pointon, Weatherall Institute of Molecular Medicine, Oxford; Graça Porto, Abel Salazar Institute for the Biomedical Sciences, Porto; Ruma Raha-Chowdhury, University of Cambridge; Kathryn Robson, Weatherall Institute of Molecular Medicine, Oxford; Jacques Rochette, University of Amiens; Marie-Paule Roth, INSERM, Toulouse; Ketil Thorstensen, University Hospital, Trondheim; Ann Walker, Royal Free Hospital, London; Victoria Wimhurst, Weatherall Institute of Molecular Medicine, Oxford; Mark Worwood, University of Wales College of Medicine.

We are grateful to the British Journal of Haematology Research Trust and the late Dr. H. Bell (Hepatology unit, Aker University Hospital, Oslo, Norway) for financial support. Travel costs for some participants were supported by the EC (QLRT-1999-02237).


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • S. Distante
    • 1
  • K. J. H. Robson
    • 2
  • J. Graham-Campbell
    • 3
  • A. Arnaiz-Villena
    • 4
  • P. Brissot
    • 5
  • Mark Worwood
    • 6
    Email author
  1. 1.Hepatology UnitAker University HospitalOsloNorway
  2. 2.MRC Molecular Haematology UnitWeatherall Institute of Molecular MedicineOxfordUK
  3. 3.Institute of ArchaeologyUniversity College LondonLondonUK
  4. 4.Department of Immunology and Molecular BiologyUniversidad ComplutenseMadridSpain
  5. 5.Clinique des Maladies du FoieINSERM U522 CHURennesFrance
  6. 6.Department of HaematologyUniversity of Wales College of MedicineCardiffUK

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