The HFE Gene
The HFE gene encodes for a protein found primarily on liver and intestinal cells that functions in detecting the amount of iron in the body. It also regulates the production of hepcidin, a protein produced by the liver that is considered the ultimate regulator of iron uptake [1].
The HFE gene is found on the short arm of the sixth chromosome [1]. It was first postulated that the genetic cause of hereditary hemochromatosis (HH) was on this chromosome when researchers noticed that HH patients had an increased frequency of the HLA-A3 allele. This allele is found on the sixth chromosome near the region that codes the MHC (Major Histocompatibility Complex). Using a positional cloning technique called linkage-disequilibrium mapping, researchers were able to pinpoint the exact location of the HFE gene. Thereafter, using DNA sequencing of RT-PCR fragments and genomic PCR products the researchers were able to sequence the genes and identify some of the common variants found in patients with hemochromatosis, such as the common C282Y mutation [2]. The sequence can be found on the right. |
Figure 1: Chromosome 6 and the location of the HFE gene[1]
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References
1. Genetics Home Reference: http://ghr.nlm.nih.gov/gene/HFE
2. Feder, J.N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D.A., Basava, A., Dormishian, F., Domingo, R., Ellis, M.C. Jr., Fullan, A., Hinton, L.M., Jones, N.L., Kimmel, B.E., Kronmal, G.S., Lauer, P., Lee, V.K., Loeb, D.B., Mapa, F.A., McClelland, E., Meyer, N.C., Mintier, G.A., Moeller, N., Moore, T., Morikang, E., Prass, C.E., Quintana, L., Starnes, S.M., Schatzman, R.C., Brunke, K.J., Drayna, D.T., Risch, N.J., Bacon, B.R., and Wolff, R.K. (1996). A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics, 13: 399-408
2. Feder, J.N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D.A., Basava, A., Dormishian, F., Domingo, R., Ellis, M.C. Jr., Fullan, A., Hinton, L.M., Jones, N.L., Kimmel, B.E., Kronmal, G.S., Lauer, P., Lee, V.K., Loeb, D.B., Mapa, F.A., McClelland, E., Meyer, N.C., Mintier, G.A., Moeller, N., Moore, T., Morikang, E., Prass, C.E., Quintana, L., Starnes, S.M., Schatzman, R.C., Brunke, K.J., Drayna, D.T., Risch, N.J., Bacon, B.R., and Wolff, R.K. (1996). A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics, 13: 399-408