title: The ethnospecific distribution of the HFE haplotypes for IVS2(+4)t/c, IVS4(-44)t/c, and IVS5(-47)g/a in populations of Russia and possible effects of these single-nucleotide polymorphisms in splicing.
abstract: OBJECTIVE
  The aim of this work was a haplotype analysis of the major mutations (C282Y, H63D, S65C) and IVS2(+4)t/c, IVS4(-44)t/c, and IVS5(-47)a/g polymorphisms of the hemochromatosis HFE gene in populations inhabiting the territories of Russia (Russians, Finno-Ugrians, Central Asians, and Arctic Mongoloids).
  
  
  METHODS
  The hemochromatosis gene (HFE) alleles were detected using the polymerase chain reaction/restriction fragment length polymorphism method.
  
  
  RESULTS
  Of the eight possible intronic haplotype variants, the TTG, TTA, CTA, and CCA were identified. The HFE alleles with the different haplotype variants were distributed in an ethnospecific manner among the populations. Our finding was that every one of the C282Y, H63D, and S65C mutations was in linkage disequilibrium only with one of the intronic haplotype variants: TTG, CTA, and CCA, respectively. The data from context analysis of DNA regions where the examined single-nucleotide polymorphisms are located suggested their involvement in splicing.
  
  
  CONCLUSIONS
  Different genotypes of the HFE gene occur at different frequencies among populations of Russia. Carriers of the specific genotype variants may potentially express distinct sets of alternative HFE mRNAs.
authors.affiliation: Laboratory of Animal Molecular Genetics, Institute of Cytology and Genetics of the Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia. mikhail@bionet.nsc.ru
authors.forename: Svetlana Vladimirovna
authors.initials: SV
authors.lastname: Mikhailova
authors.forename: Vladimir Nikolaevich
authors.initials: VN
authors.lastname: Babenko
authors.forename: Mikhail Ivanovich
authors.initials: MI
authors.lastname: Voevoda
authors.forename: Aida Gerasimovna
authors.initials: AG
authors.lastname: Romashchenko
mesh_terms: D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D005828:Genetics, Population; D006239:Haplotypes; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics*; D010802:Phylogeny; D011110:Polymorphism, Genetic / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D012326:RNA Splicing / Q000235:genetics*; D012426:Russia
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins