Skip to main content
SpringerLink
Log in

The origin and spread of the HFE-C282Y haemochromatosis mutation

  • Review Article
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1a, b
Fig. 2a-c
Fig. 3a-c

Similar content being viewed by others

References

  • Adams PC (1994) Prevalence of abnormal iron studies in heterozygotes for hereditary hemochromatosis: an analysis of 255 heterozygotes. Am J Hematol 45:146–149

    CAS  PubMed  Google Scholar 

  • Ajioka RS, Jorde LB, Gruen JR, Yu P, Dimitrova D, Barrow J, Radisky E, Edwards CQ, Griffen LM, Kushner JP (1997) Haplotype analysis of hemochromatosis: evaluation of different linkage-disequilibrium approaches and evolution of disease chromosomes. Am J Hum Genet 60:1439–1447

    CAS  PubMed  Google Scholar 

  • Arnaiz-Viellena A, Rodrigues de Cordoba S, Vela F, Pascual JC, Cervero J, Bootello A (1981) HLA antigens in a sample of the Spanish population: common features among Spaniards, Basques and Sardinians. Hum Genet 58:344–348

    PubMed  Google Scholar 

  • Arnaiz-Villena A (2001) Historic genomics: an emergent discipline. Hum Immunol 62:869–870

    Article  CAS  Google Scholar 

  • Arnaiz-Villena A, Martinezlaso J, Gomezcasado E, Diazcampos N, Santos P, Martinho A, Bredacoimbra H (1997) Relatedness among Basques, Portuguese, Spaniards, and Algerians studied by HLA allelic frequencies and haplotypes. Immunogenetics 47:37–43

    Article  CAS  PubMed  Google Scholar 

  • Arnaiz-Villena A, Gomez-Casdo E, Martinez-Laso J (2002) Population genetic relationships between Mediterranean populations determined by HLA allele distribution and a historic perspective. Tissue Antigens 60:111–121

    Article  CAS  PubMed  Google Scholar 

  • Asberg A, Hveem K, Thorstensen K, Ellekjaer E, Kannelonning K, Fjosne U, Halvorsen TB, Smethurst HBG, Sagen E, Bjerve KS (2001) Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastro 36:1108–1115

    Article  CAS  Google Scholar 

  • Batey C, Clarke H, Page RI, Price NS (1994) Cultural atlas of the Viking world. Andromeda, Oxford

  • Beutler E, Gelbart T, West C, Lee P, Adams M, Blackstone R, Pockros P, Kosty M, Venditti CP, Phatak PD, Seese NK, Chorney KA, Tenelshof AE, Gerhard GS, Chorney M (1996) Mutation analysis in hereditary hemochromatosis. Blood Cells Mol Dis 22:187–194

    Article  CAS  PubMed  Google Scholar 

  • Beutler E, Felitti V, Gelbart T, Ho N (2000) The effect of HFE genotypes on measurements of iron overload in patients attending a health appraisal clinic. Ann Int Med 133:329–337

    CAS  PubMed  Google Scholar 

  • Beutler E, Felitti VJ, Koziol JA, Ho NJ, Gelbart T (2002) Penetrance of 845G>A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 359:211–218

    Article  PubMed  Google Scholar 

  • Beutler E, Felitti V, Gelbart T, Waalen J (2003) Haematological effects of the C282Y HFE mutation in homozygous and heterozygous states among subjects of northern and southern European ancestry. Br J Haematol 120:887–893

    Article  CAS  PubMed  Google Scholar 

  • Blanco I, Fernandez E, Bustillo EF (2001) Alpha-1-antitrypsin PI phenotypes S and Z in Europe: an analysis of the published surveys. Clin Genet 60:31–41

    Article  CAS  PubMed  Google Scholar 

  • Bothwell TH, Macphail AP (1998) Hereditary hemochromatosis: etiologic, pathologic, and clinical aspects. Semin Hematol 35:55–71

    CAS  PubMed  Google Scholar 

  • Bulaj ZJ, Griffen LM, Jorde LB, Edwards CQ, Kushner JP (1996) Clinical and biochemical abnormalities in people heterozygous for hemochromatosis. N Engl J Med 335:1799–1805

    Article  CAS  PubMed  Google Scholar 

  • Burt MJ, George PM, Upton JD, Collett JA, Frampton CMA, Chapman TM, Walmsley TA, Chapman BA (1998) The significance of haemochromatosis gene mutations in the general population: implications for screening. Gut 43:830–836

    CAS  PubMed  Google Scholar 

  • Byrnes V, Ryan E, Barrett S, Kenny P, Mayne P, Crowe J (2001) Genetic hemochromatosis, a Celtic disease: is it now time for population screening? Genet Test 5:127–130

    Article  CAS  PubMed  Google Scholar 

  • Campbell S, George DK, Robb SD, Spooner R, McDonagh TA, Dargie HJ, Mills PR (2003) The prevalence of haemochromatosis gene mutations in the West of Scotland and their relation to ischaemic heart disease. Heart 89:1023–1026

    Article  CAS  PubMed  Google Scholar 

  • Camaschella C, Roetto A, De Gobbi M (2002) Genetic haemochromatosis: genes and mutations associated with iron loading. Best Pract Res Clin Haematol 15:261–276

    Article  CAS  PubMed  Google Scholar 

  • Cardoso CS, Alves H, Mascarenhas M, Goncalves R, Oliveira P, Rodrigues P, Cruz E, de Sousa M, Porto G (2002) Co-selection of the H63D mutation and the HLA-A29 allele: a new paradigm of linkage disequilibrium? Immunogenetics 53:1002–1008

    Article  CAS  PubMed  Google Scholar 

  • Cavalli-Sforza L, Mennozzi P, Piazza A (1994) The history and geography of human genes. Princeton University Press, Princeton

  • Clayton, Lonjou C (1996) Allele and haplotype frequencies for HLA loci in various ethnic groups. In: Charron D (ed) Genetic diversity of HLA, functional and medical implications. EDK, Paris, pp 650–820

  • Crawford DHG, Powell LW, Leggett BA, Francis JS, Fletcher LM, Webb SI, Halliday JW, Jazwinska EC (1995) Evidence that the ancestral haplotype in Australian hemochromatosis patients may be associated with a common mutation in the gene. Am J Hum Genet 57:362–367

    CAS  PubMed  Google Scholar 

  • Cunliffe B (2003) The ancient Celts. Oxford University Press, Oxford

  • Darke C, Guttridge MG, Thompson J, McNamara S, Street J, Thomas M (1998) HLA class I (A, B) and II (DR, DQ) gene and haplotype frequencies in blood donors from Wales. Immunogenetics 15:69–83

    Article  CAS  Google Scholar 

  • Darke C, Guttridge MG, Mcnamara S (1999) Distribution of HFE alleles and HLA-HFE haplotypes in blood donors resident in Wales. Eur J Immunogenet 25 (Suppl 3):263

    Google Scholar 

  • Datz C, Haas T, Rinner H, Sandhofer F, Patsch W, Paulweber B (1998) Heterozygosity for the C282Y mutation in the hemochromatosis gene is associated with increased serum iron, transferrin saturation, and hemoglobin in young women: a protective role against iron deficiency? Clin Chem 44:2429–2432

    CAS  PubMed  Google Scholar 

  • De Braekeleer M (1993) A prevalence and fertility study of haemochromatosis in Saguenay-Lac-Saint-Jean. Ann Hum Biol 20:501–505

    PubMed  Google Scholar 

  • De Serres FJ (2002) Worldwide racial and ethnic distributioin of α1-antitrypsin deficiency. Chest 122:1818–1829

    Article  PubMed  Google Scholar 

  • Eisensmith RC, Okano Y, Dasovich M, Wang T, Guttler F, Lou H, Guldberg P, Lichterkonecki U, Konecki DS, Svensson E, Hagenfeldt L, Rey F, Munnich A, Lyonnet S, Cockburn F, Connor JM, Pembrey ME, Smith I, Gitzelmann R, Steinmann B, Apold J, Eiken HG, Giovannini M, Riva E, Longhi R, Romano C, Cerone R, Naughten ER, Mullins C, Cahalane S, Ozalp I, Fekete G, Schuler D, Berencsi GY, Nasz I, Brdicka R, Kamaryt J, Pijackova A, Cabalska B, Boszkowa K, Schwartz E, Kalinin VN, Jin L, Chakraborty R, Woo SLC (1992) Multiple origins for phenylketonuria in Europe. Am J Hum Genet 51:1355–1365

    CAS  PubMed  Google Scholar 

  • Eisensmith RC, Goltsov AA, Oneill C, Tyfield LA, Schwartz EI, Kuzmin AI, Baranovskaya SS, Tsukerman GL, Treacy E, Scriver CR, Guttler F, Guldberg P, Eiken HG, Apold J, Svensson E, Naughten E, Cahalane SF, Croke DT, Cockburn F, Woo SLC (1995) Recurrence of the R408W mutation in the phenylalanine-hydroxylase locus in Europeans. Am J Hum Genet 56:278–286

    CAS  PubMed  Google Scholar 

  • Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, Mcclelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408

    CAS  PubMed  Google Scholar 

  • Feder JN, Tsuchihashi Z, Irrinki A, Lee VK, Mapa FA, Morikang E, Prass CE, Starnes SM, Wolff RK, Parkkila S, Sly WS, Schatzman RC (1997) The hemochromatosis founder mutation in HLA-H disrupts beta(2)-microglobulin interaction and cell surface expression. J Biol Chem 272:14025–14028

    Article  CAS  PubMed  Google Scholar 

  • Feder JN, Penny DM, Irrinki A, Lee VK, Lebron JA, Watson N, Tsuchihashi Z, Sigal E, Bjorkman PJ, Schatzman RC (1998) The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc Natl Acad Sci USA 95:1472–1477

    Article  CAS  PubMed  Google Scholar 

  • Finch T, Lawlor E, Borton M, Barnes CA, McNamara S, Oriordan J, McCann SR, Darke C (1997) Distribution of HLA-A, B and DR genes and haplotypes in the Irish population. Exp Clin Immunogenet 14:250–263

    CAS  PubMed  Google Scholar 

  • Ganz T (2003) Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 102:783–788

    Article  CAS  PubMed  Google Scholar 

  • Gkiasta M, Russell T, Shennan S, Steele J (2003) Neolithic transition in Europe: the radiocarbon record revisited. Antiquity 77:45–62

    Google Scholar 

  • Helgason A, Hickey E, Goodacre S, Bosnes V, Stefansson K, Ward R, Sykes B (2001) mtDNA and the islands of the north Atlantic: estimating the proportions of Norse and Gaelic ancestry. Am J Hum Genet 68:723–737

    Article  CAS  PubMed  Google Scholar 

  • Jackson HA, Carter K, Darke C, Guttridge MG, Ravine D, Hutton RD, Napier JA, Worwood M (2001) HFE mutations, iron deficiency and overload in 10,500 blood donors. Br J Haematol 114:474–484

    Article  PubMed  Google Scholar 

  • Kaplan NL, Lewis PO, Weir BS (1994) Age of the delta-F508 cystic-fibrosis mutation. Nat Genet 8:216

    CAS  PubMed  Google Scholar 

  • Krawczak M, Zschocke J (2003) A role for overdominant selection in phenylketonuria? Evidence from molecular data. Hum Mutat 21:394–397

    Article  CAS  PubMed  Google Scholar 

  • Lebron JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, Mintier GA, Feder JN, Bjorkman PJ (1998) Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 93:111–123

    Article  CAS  PubMed  Google Scholar 

  • Lucotte G (2001) Frequency analysis and allele map in favor of the Celtic origin of the C282Y mutation of hemochromatosis. Blood Cells Mol Dis 27:549–556

    Article  CAS  PubMed  Google Scholar 

  • Lucotte G, Dieterlen F (2003) A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation? Blood Cells Mol Dis 31:262–267

    Article  CAS  PubMed  Google Scholar 

  • Luisetti M, Seersholm N (2004) α1-Antitrypsin deficiency. 1: epidemiology of α1-antitrypsin deficiency. Thorax 59:164–169

    Article  CAS  PubMed  Google Scholar 

  • Malfroy L, Roth MP, Carrington M, Borot N, Volz A, Ziegler A, Coppin H (1997) Heterogeneity in rates of recombination in the 6-Mb region telomeric to the human major histocompatibility complex. Genomics 43:226–231

    Article  CAS  PubMed  Google Scholar 

  • McCune CA, Al-Jader LN, May A, Hayes SL, Jackson HA, Worwood M (2002) Hereditary haemochromatosis: only 1% of adult HFE C282Y homozygotes in South Wales have a clinical diagnosis of iron overload. Hum Genet 111:538–543

    Article  CAS  PubMed  Google Scholar 

  • McEvedy C (2002) The new Penguin atlas of ancient history. Penguin Books, London

  • Merryweather-Clarke AT, Pointon JJ, Jouanolle AM, Rochette J, Robson KJH (2000) Georgraphy of HFE C282Y and H63D mutations. Genet Test 4:183–198

    Article  CAS  PubMed  Google Scholar 

  • Milman N, Pedersen P (2003) Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in Southern Scandinavia and spread with the Vikings. Clin Genet 64:36–47

    Article  CAS  PubMed  Google Scholar 

  • Milman N, Sorensen SA (1983) Idiopathic haemochromatosis. Was the ancestor a Danish Viking? Ugeskr Laeger 145:832–833

    Google Scholar 

  • Moalem S, Percy ME, Kruck TPA, Gelbart RR (2002) Epidemic pathogenic selection: an explanation for hereditary hemochromatosis? Med Hypotheses 59:325–329

    Article  PubMed  Google Scholar 

  • Moirand R, Guyader D, Mendler MH, Jouanolle AM, Le Gall JY, David V, Brissot P, Deugnier Y (2002) HFE based re-evaluation of heterozygous hemochromatosis. Am J Med Genet 111:356–361

    Article  PubMed  Google Scholar 

  • Morral N, Bertranpetit J, Estivill X, Nunes V, Casals T, Gimenez J, Reis A, Varonmateeva R, Macek M, Kalaydjieva L, Angelicheva D, Dancheva R, Romeo G, Russo MP, Garnerone S, Restagno G, Ferrari M, Magnani C, Claustres M, Desgeorges M, Schwartz M, Schwarz M, Dallapiccola B, Novelli G, Ferec C, Dearce M, Nemeti M, Kere T, Anvret M, Dahl N, Kadasi L (1994) The origin of the major cystic-fibrosis mutation (delta-F508) in European populations. Nat Genet 7:169–175

    CAS  PubMed  Google Scholar 

  • Motulsky AG (1979) Genetics of hemochromatosis. N Engl J Med 301:1291

    CAS  Google Scholar 

  • Muller CR, Ehninger G, Goldmann SF (2003) Gene and haplotype frequencies for the loci HLA-A, HLA-B, and HLA-DR based on over 13,000 German blood donors. Hum Immunol 64:137–151

    Article  PubMed  Google Scholar 

  • Mura C, Raguenes O, Ferec C (1999) HFE mutations in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood 93:2202–2205

    PubMed  Google Scholar 

  • Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S (2001) Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (Usf2) knockout mice. Proc Natl Acad Sci USA 98:8780–8785

    Article  CAS  PubMed  Google Scholar 

  • Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G (1996) Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110:1107–1119

    CAS  PubMed  Google Scholar 

  • Olsson KS, Ritter B (1981) Idiopatisk hemokromatose. Tidsskrift for Den Norske Laegeforen 29:101

    Google Scholar 

  • Papanikolaou G, Politou M, Terpos E, Fourlemadis S, Sakellaropoulos N, Loukopoulos D (2000) Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity. Blood Cells Mol Dis 26:163–168

    Article  CAS  PubMed  Google Scholar 

  • Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, l’Oréal O (2001) A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276:7811–7819

    Article  CAS  PubMed  Google Scholar 

  • Piperno A, Arosio C, Fargion S, Roetto A, Nicoli C, Girelli D, Sbaiz L, Gasparini P, Boari G, Sampietro M, Camaschella C (1996) The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients. Hepatology 24:43–46

    Article  CAS  PubMed  Google Scholar 

  • Piperno A, Sampietro M, Pietrangelo A, Arosio C, Lupica L, Montosi G, Vergani A, Fraquelli M, Girelli D, Pasquero P, Roetto A, Gasparini P, Fargion S, Conte D, Camaschella C (1998) Heterogeneity of hemochromatosis in Italy. Gastroenterology 114:996–1002

    CAS  PubMed  Google Scholar 

  • Powell LW, Summers KM, Board PG, Axelsen E, Webb S, Halliday JW (1990) Expression of hemochromatosis in homozygous subjects. Implications for early diagnosis and prevention. Gastroenterology 98:1625–1632

    CAS  PubMed  Google Scholar 

  • Price P, Witt C, Allcock R, Sayer D, Garlepp M, Kok CC, French M, Mallal S, Christiansen F (1999) The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immuopathological diseases. Immunol Rev 167:257–274

    CAS  PubMed  Google Scholar 

  • Raha-Chowdhury, Gruen JR (2000) Localization, allelic heterogeneity, and origins of the hemochromatosis gene. In: Barton JC, Edwards CQ (eds) Hemochromatosis: genetics, pathophysiology, diagnosis and treament. Cambridge University Press, Cambridge, pp 75–90

  • Raha-Chowdhury R, Bowen DJ, Stone C, Pointon JJ, Terwilliger JD, Shearman JD, Robson KJH, Bomford A, Worwood M (1995) New polymorphic microsatellite markers place the haemochromatosis gene telomeric to D6S105. Hum Mol Genet 4:1869–1874

    CAS  PubMed  Google Scholar 

  • Richards HD (2000) Viking age England. Tempus, Stroud

  • Risch N (1997) Haemochromatosis, HFE and genetic complexity. Nat Genet 17:375–376

    CAS  PubMed  Google Scholar 

  • Rochette J, Pointon JJ, Fisher CA, Perera G, Arambepola M, Arichchi DSK, De Silva S, Vandwalle JL, Monti JP, Old JM, Merryweather-Clarke AT, Weatherall DJ, Robson KJH (1999) Multicentric origin of hemochromatosis gene (HFE) mutations. Am J Hum Genet 64:1056–1062

    Article  CAS  PubMed  Google Scholar 

  • Rossi E, Olynyk JK, Cullen DJ, Papadopoulos G, Bulsara M, Summerville L, Powell LW (2000) Compound heterozygous hemochromatosis genotype predicts increased iron and erythrocyte indices in women. Clin Chem 46:162–166

    CAS  PubMed  Google Scholar 

  • Sabeti PC, Reich DE, Higgins JM, Levine HZP, Richter DJ, Schaffner SF, Gabriel SB, Platko JV, Patterson NJ, McDonald GJ, Ackerman HC, Campbell SJ, Altshuler DCR, Kwiatkowski D, Ward R, Lander ES (2002) Detecting recent positive selection in the human genome from haplotype structure. Nature 419:832–837

    Article  CAS  PubMed  Google Scholar 

  • Schipper RF, Damaro J, Bakker JT, Vanrood JJ, Oudshoorn M (1997) HLA gene and haplotype frequencies in bone marrow donors worldwide registries. Hum Immunol 52:54–71

    Article  CAS  PubMed  Google Scholar 

  • Simon M, Pawlotsky Y, Bourel M, Fauchet R, Genetet B (1975) Hémochromatose idopathique. Maladie associée à l’antigène tissulaire HL-A3? Nouvelle Presse Med 4:1432

    CAS  Google Scholar 

  • Simon M, Alexandre A, Fauchet R, Genetet B, Bourel M (1980) The genetics of hemochromatosis. In: Steinberg AG, Bearn AG, Motulsky AG, Childs B (eds) Progress in medical genetics. Saunders, Philadelphia, pp 135–168

  • Smith JM, Haigh J (1974) The hitch-hiking effect of a favourable gene. Genet Res 23:23–25

    PubMed  Google Scholar 

  • Thomas J (2003) Thoughts on the ‘repacked’ Neolithic revolution. Antiquity 77:67–74

    Google Scholar 

  • Thomas W, Fullan A, Loeb DB, Mcclelland EE, Bacon BR, Wolff RK (1998) A haplotype and linkage disequilibrium analysis of the hereditary hemochromatosis gene region. Hum Genet 102:517–525

    Article  CAS  PubMed  Google Scholar 

  • Weale ME, Weiss DA, Jager RF, Bradman N, Thomas MG (2002) Y chromosome evidence for Anglo-Saxon mass migration. Mol Biol and Evol 19:1008–1021

    CAS  Google Scholar 

  • Willis G, Scott DGI, Jennings BA, Smith K, Bukhari M, Wimperis JZ (2002) HFE mutations in an inflammatory arthritis population. Rheumatology 41:176–179

    Article  CAS  PubMed  Google Scholar 

  • Wilson JF, Weiss DA, Richards M, Thomas MG, Bradman N, Goldstein DB (2001) Genetic evidence for different male and female roles during cultural transitions in the British Isles. Proc Natl Acad Sci USA 98:5078–5083

    Article  CAS  PubMed  Google Scholar 

  • Yaouanq J (2000) Human leukocyte antigen (HLA) assocoiation and typing in hemochromatosis. In: Barton JC, Edwards CQ (eds) Hemochromatosis: genetics, pathophysiology, diagnosis and treatment. Cambridge University Press, Cambridge, pp 63–74

  • Zhou XY, Tomatsu S, Fleming RE, Parkkila S, Waheed A, Jiang JX, Fei Y, Brunt EM, Ruddy DA, Prass CE, Schatzman RC, Oneill R, Britton RS, Bacon BR, Sly WS (1998) HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc Natl Acad Sci USA 95:2492–2497

    Article  CAS  PubMed  Google Scholar 

  • Zschocke J (2003) Phenylketonuria mutations in Europe. Hum Mutat 21:345–356

    Article  CAS  PubMed  Google Scholar 

  • Zschocke J, Mallory JP, Eiken HG, Nevin NC (1997) Phenylketonuria and the peoples of Northern Ireland. Hum Genet 100:189–194

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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).

Author information

Authors and Affiliations

  1. Hepatology Unit, Aker University Hospital, Oslo, Norway

    S. Distante

  2. MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK

    K. J. H. Robson

  3. Institute of Archaeology, University College London, London, UK

    J. Graham-Campbell

  4. Department of Immunology and Molecular Biology, Universidad Complutense, Hosp 12 Octubre, Madrid, Spain

    A. Arnaiz-Villena

  5. Clinique des Maladies du Foie, INSERM U522 CHU, Rennes, France

    P. Brissot

  6. Department of Haematology, University of Wales College of Medicine, Cardiff, CF14 4XN, UK

    Mark Worwood

Authors
  1. S. Distante
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. J. H. Robson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Graham-Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Arnaiz-Villena
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Brissot
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark Worwood
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Worwood.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Distante, S., Robson, K.J.H., Graham-Campbell, J. et al. The origin and spread of the HFE-C282Y haemochromatosis mutation. Hum Genet 115, 269–279 (2004). https://doi.org/10.1007/s00439-004-1152-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-004-1152-4

Keywords

Search

Navigation