Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload in the South African population

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dc.contributor.advisor Zaahl, M. G.
dc.contributor.advisor Warnich, L.
dc.contributor.advisor Robson, K. J. H.
dc.contributor.author Booley, Fadwah en_ZA
dc.contributor.other University of Stellenbosch. Faculty of Agrisciences. Dept. of Genetics.
dc.date.accessioned 2008-06-30T12:22:00Z en_ZA
dc.date.accessioned 2010-06-01T08:43:40Z
dc.date.available 2008-06-30T12:22:00Z en_ZA
dc.date.available 2010-06-01T08:43:40Z
dc.date.issued 2007-03 en_ZA
dc.identifier.uri http://hdl.handle.net/10019.1/2220
dc.description Thesis (MSc (Genetics))—University of Stellenbosch, 2007.
dc.description.abstract Hereditary haemochromatosis (HH), a common autosomal recessive disease, is characterized by increased iron absorption leading to progressive iron accumulation in organs such as the liver, heart and pancreas. In the South African population the disease is prevalent in individuals of Caucasian origin, with a carrier frequency of one in six for the C282Y mutation in the HFE gene. We investigated the role of genes implicated in iron metabolism, including the high-iron gene (HFE), haem oxgenase-1 gene (HMOX1), solute carrier family 40 (iron-regulated transporter) member 1 gene (SLC40A1), cytochrome b reductase gene (CYBRD1), hepcidin antimicrobial peptide gene (HAMP) and the hemojuvelin gene (HJV) in a patient cohort with non-HFE iron overload. DNA analysis was performed on samples from 36 unrelated South African Caucasian patients presenting with primary iron overload, who tested either negative or heterozygous for C282Y. In this study, mutation screening was performed by PCR amplification and HEX-SSCP analysis. Sixteen previously described and two novel variants were identified by semi-automated DNA sequencing. Common variants identified in the HFE gene included C282Y, H63D, IVS2+4T→C, IVS4-44T→C, IVS4+48G→A and IVS5-47G→A. The Q127H mutation in exon 3 of the HFE gene was identified in one patient, who tested negative for both C282Y and H63D. Mutation S65C was identified only in the population-matched controls and was absent in the patient group. Other previously described polymorphisms identified included the IVS5+51delTGGCTGTCTGACT deletion in HMOX1, I109 and V221 in SLC40A1, IVS1-4C→G, IVS2+8T→C and S266N, in the CYBRD1 gene and, S264 and A310G in the HJV gene. The novel variants, -89C→T, in the promoter region of the CYBRD1 gene, was detected in only one patient, while S333 in exon 4 of the HJV gene was present in three patients. These variants were not identified in any of the population-matched controls screened and could explain the non-HFE iron overload presented by these patients. This study clearly demonstrates the importance of modifier genes in patients with iron overload that cannot be explained by the common C282Y mutation. Studies on iron-related genes and the identification of mutations in these genes in non-HFE patients could lead to improved diagnosis and counselling of South African patients presenting with primary iron overload. en_ZA
dc.language.iso en en_ZA
dc.publisher Stellenbosch : University of Stellenbosch
dc.subject Iron -- Physiological effect en
dc.subject Hemochromatosis -- South Africa --Genetic aspects en
dc.subject Iron -- Metabolism -- Disorders -- South Africa en
dc.subject Dissertations -- Genetics en
dc.subject Theses -- Genetics en
dc.title Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload in the South African population en
dc.type Thesis en_ZA
dc.rights.holder University of Stellenbosch


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