A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis

Nat Genet. 1996 Aug;13(4):399-408. doi: 10.1038/ng0896-399.

Abstract

Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.

Publication types

  • Comparative Study

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Biological Evolution
  • Chromosomes, Artificial, Yeast
  • Chromosomes, Human, Pair 6
  • Cloning, Molecular / methods
  • Cysteine
  • DNA Primers / chemistry
  • Gene Expression
  • Genes, MHC Class I
  • Genetic Markers
  • HLA Antigens / genetics*
  • Haplotypes
  • Hemochromatosis / genetics*
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Linkage Disequilibrium
  • Major Histocompatibility Complex
  • Membrane Proteins*
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • DNA Primers
  • Genetic Markers
  • HFE protein, human
  • HLA Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • RNA, Messenger
  • Cysteine

Associated data

  • GENBANK/U60319