title: Significance of linkage disequilibrium between mutation C282Y and a MseI polymorphism in population screening and DNA diagnosis of hemochromatosis.
abstract: An increasing number of studies demonstrate a lack of phenotypic expression in subjects found to be homozygous for the common hereditary hemochromatosis (HH) mutation, C282Y. In this study the impact of possible overestimation of C282Y homozygosity, as a consequence of a MseI polymorphism identified in intron 4 of the HFE gene, was investigated in South African subjects. Utilization of a modified polymerase chain reaction (PCR)-based assay highlighted the potential implications with respect to genotype/phenotype correlation studies, particularly in the general population. Mistyping rather than lack of disease association provides a plausible explanation for the phenomenon of C282Y homozygosity without iron overload. Reassessment of C282Y mutation status in such cases may result in justified population screening in HH.
authors.affiliation: Division of Human Genetics, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa.
authors.forename: J N
authors.initials: JN
authors.lastname: de Villiers
authors.forename: M J
authors.initials: MJ
authors.lastname: Kotze
mesh_terms: D004247:DNA; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D006580:Genetic Carrier Screening / Q000379:methods; D006432:Hemochromatosis / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008403:Mass Screening / Q000379:methods*; D009154:Mutation; D011110:Polymorphism, Genetic; D015995:Prevalence; D013019:South Africa / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D004247:DNA; C055927:endodeoxyribonuclease MseI; D015252:Deoxyribonucleases, Type II Site-Specific