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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Aug;57(2):362–367.

Evidence that the ancestral haplotype in Australian hemochromatosis patients may be associated with a common mutation in the gene.

D H Crawford 1, L W Powell 1, B A Leggett 1, J S Francis 1, L M Fletcher 1, S I Webb 1, J W Halliday 1, E C Jazwinska 1
PMCID: PMC1801553  PMID: 7668262

Abstract

Hemochromatosis (HC) is a common inherited disorder of iron metabolism for which neither the gene nor biochemical defect have yet been identified. The aim of this study was to look for clinical evidence that the predominant ancestral haplotype in Australian patients is associated with a common mutation in the gene. We compared indices of iron metabolism and storage in three groups of HC patients categorized according to the presence of the ancestral haplotype (i.e., patients with two copies, one copy, and no copies of the ancestral haplotype). We also examined iron indices in two groups of HC heterozygotes (those with the ancestral haplotype and those without) and in age-matched controls. These analyses indicate that (i) HC patients with two copies of the ancestral haplotype show significantly more severe expression of the disorder than those with one copy or those without, (ii) HC heterozygotes have partial clinical expression, which may be influenced by the presence of the ancestral haplotype in females but not in males, and (iii) the high population frequency of the HC gene may be the result of the selective advantage conferred by protecting heterozygotes against iron deficiency.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams P. C. Prevalence of abnormal iron studies in heterozygotes for hereditary hemochromatosis: an analysis of 255 heterozygotes. Am J Hematol. 1994 Feb;45(2):146–149. doi: 10.1002/ajh.2830450210. [DOI] [PubMed] [Google Scholar]
  2. Bassett M. L., Halliday J. W., Powell L. W. Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology. 1986 Jan-Feb;6(1):24–29. doi: 10.1002/hep.1840060106. [DOI] [PubMed] [Google Scholar]
  3. Cartwright G. E., Edwards C. Q., Kravitz K., Skolnick M., Amos D. B., Johnson A., Buskjaer L. Hereditary hemochromatosis. Phenotypic expression of the disease. N Engl J Med. 1979 Jul 26;301(4):175–179. doi: 10.1056/NEJM197907263010402. [DOI] [PubMed] [Google Scholar]
  4. Crawford D. H., Halliday J. W., Summers K. M., Bourke M. J., Powell L. W. Concordance of iron storage in siblings with genetic hemochromatosis: evidence for a predominantly genetic effect on iron storage. Hepatology. 1993 May;17(5):833–837. [PubMed] [Google Scholar]
  5. Doran T. J., Bashir H. V., Trejaut J., Bassett M. L., Halliday J. W., Powell L. W. Idiopathic haemochromatosis in the Australian population: HLA linkage and recessivity. Hum Immunol. 1981 May;2(3):191–200. doi: 10.1016/0198-8859(81)90011-2. [DOI] [PubMed] [Google Scholar]
  6. Edwards C. Q., Carroll M., Bray P., Cartwright G. E. Hereditary hemochromatosis. Diagnosis in siblings and children. N Engl J Med. 1977 Jul 7;297(1):7–13. doi: 10.1056/NEJM197707072970102. [DOI] [PubMed] [Google Scholar]
  7. Jazwinska E. C., Lee S. C., Webb S. I., Halliday J. W., Powell L. W. Localization of the hemochromatosis gene close to D6S105. Am J Hum Genet. 1993 Aug;53(2):347–352. [PMC free article] [PubMed] [Google Scholar]
  8. Jazwinska E. C., Pyper W. R., Burt M. J., Francis J. L., Goldwurm S., Webb S. I., Lee S. C., Halliday J. W., Powell L. W. Haplotype analysis in Australian hemochromatosis patients: evidence for a predominant ancestral haplotype exclusively associated with hemochromatosis. Am J Hum Genet. 1995 Feb;56(2):428–433. [PMC free article] [PubMed] [Google Scholar]
  9. Kerem E., Corey M., Kerem B. S., Rommens J., Markiewicz D., Levison H., Tsui L. C., Durie P. The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508). N Engl J Med. 1990 Nov 29;323(22):1517–1522. doi: 10.1056/NEJM199011293232203. [DOI] [PubMed] [Google Scholar]
  10. Leggett B. A., Brown N. N., Bryant S. J., Duplock L., Powell L. W., Halliday J. W. Factors affecting the concentrations of ferritin in serum in a healthy Australian population. Clin Chem. 1990 Jul;36(7):1350–1355. [PubMed] [Google Scholar]
  11. Muir W. A., McLaren G. D., Braun W., Askari A. Evidence for heterogeneity in hereditary hemochromatosis. Evaluation of 174 persons in nine families. Am J Med. 1984 May;76(5):806–814. doi: 10.1016/0002-9343(84)90991-4. [DOI] [PubMed] [Google Scholar]
  12. Petrukhin K., Fischer S. G., Pirastu M., Tanzi R. E., Chernov I., Devoto M., Brzustowicz L. M., Cayanis E., Vitale E., Russo J. J. Mapping, cloning and genetic characterization of the region containing the Wilson disease gene. Nat Genet. 1993 Dec;5(4):338–343. doi: 10.1038/ng1293-338. [DOI] [PubMed] [Google Scholar]
  13. Powell L. W., Summers K. M., Board P. G., Axelsen E., Webb S., Halliday J. W. Expression of hemochromatosis in homozygous subjects. Implications for early diagnosis and prevention. Gastroenterology. 1990 Jun;98(6):1625–1632. doi: 10.1016/0016-5085(90)91100-k. [DOI] [PubMed] [Google Scholar]
  14. Sheppard D. N., Rich D. P., Ostedgaard L. S., Gregory R. J., Smith A. E., Welsh M. J. Mutations in CFTR associated with mild-disease-form Cl- channels with altered pore properties. Nature. 1993 Mar 11;362(6416):160–164. doi: 10.1038/362160a0. [DOI] [PubMed] [Google Scholar]
  15. Simon M., Bourel M., Fauchet R., Genetet B. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut. 1976 May;17(5):332–334. doi: 10.1136/gut.17.5.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Summers K. M., Halliday J. W., Powell L. W. Identification of homozygous hemochromatosis subjects by measurement of hepatic iron index. Hepatology. 1990 Jul;12(1):20–25. doi: 10.1002/hep.1840120105. [DOI] [PubMed] [Google Scholar]
  17. Thomas G. R., Forbes J. R., Roberts E. A., Walshe J. M., Cox D. W. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet. 1995 Feb;9(2):210–217. doi: 10.1038/ng0295-210. [DOI] [PubMed] [Google Scholar]
  18. Yip R., Johnson C., Dallman P. R. Age-related changes in laboratory values used in the diagnosis of anemia and iron deficiency. Am J Clin Nutr. 1984 Mar;39(3):427–436. doi: 10.1093/ajcn/39.3.427. [DOI] [PubMed] [Google Scholar]

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