title: A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.
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.
authors.affiliation: Mercator Genetics, Inc., Menlo Park, California 94025, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Feder
authors.forename: A
authors.initials: A
authors.lastname: Gnirke
authors.forename: W
authors.initials: W
authors.lastname: Thomas
authors.forename: Z
authors.initials: Z
authors.lastname: Tsuchihashi
authors.forename: D A
authors.initials: DA
authors.lastname: Ruddy
authors.forename: A
authors.initials: A
authors.lastname: Basava
authors.forename: F
authors.initials: F
authors.lastname: Dormishian
authors.forename: R
authors.initials: R
authors.lastname: Domingo
authors.forename: M C
authors.initials: MC
authors.lastname: Ellis
authors.forename: A
authors.initials: A
authors.lastname: Fullan
authors.forename: L M
authors.initials: LM
authors.lastname: Hinton
authors.forename: N L
authors.initials: NL
authors.lastname: Jones
authors.forename: B E
authors.initials: BE
authors.lastname: Kimmel
authors.forename: G S
authors.initials: GS
authors.lastname: Kronmal
authors.forename: P
authors.initials: P
authors.lastname: Lauer
authors.forename: V K
authors.initials: VK
authors.lastname: Lee
authors.forename: D B
authors.initials: DB
authors.lastname: Loeb
authors.forename: F A
authors.initials: FA
authors.lastname: Mapa
authors.forename: E
authors.initials: E
authors.lastname: McClelland
authors.forename: N C
authors.initials: NC
authors.lastname: Meyer
authors.forename: G A
authors.initials: GA
authors.lastname: Mintier
authors.forename: N
authors.initials: N
authors.lastname: Moeller
authors.forename: T
authors.initials: T
authors.lastname: Moore
authors.forename: E
authors.initials: E
authors.lastname: Morikang
authors.forename: C E
authors.initials: CE
authors.lastname: Prass
authors.forename: L
authors.initials: L
authors.lastname: Quintana
authors.forename: S M
authors.initials: SM
authors.lastname: Starnes
authors.forename: R C
authors.initials: RC
authors.lastname: Schatzman
authors.forename: K J
authors.initials: KJ
authors.lastname: Brunke
authors.forename: D T
authors.initials: DT
authors.lastname: Drayna
authors.forename: N J
authors.initials: NJ
authors.lastname: Risch
authors.forename: B R
authors.initials: BR
authors.lastname: Bacon
authors.forename: R K
authors.initials: RK
authors.lastname: Wolff
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D018244:Chromosomes, Artificial, Yeast; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular / Q000379:methods; D003545:Cysteine; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D005805:Genes, MHC Class I; D005819:Genetic Markers; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012333:RNA, Messenger; D003545:Cysteine