title: Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project.
abstract: The human major histocompatibility complex (MHC) is contained within about 4 Mb on the short arm of chromosome 6 and is recognised as the most variable region in the human genome. The primary aim of the MHC Haplotype Project was to provide a comprehensively annotated reference sequence of a single, human leukocyte antigen-homozygous MHC haplotype and to use it as a basis against which variations could be assessed from seven other similarly homozygous cell lines, representative of the most common MHC haplotypes in the European population. Comparison of the haplotype sequences, including four haplotypes not previously analysed, resulted in the identification of >44,000 variations, both substitutions and indels (insertions and deletions), which have been submitted to the dbSNP database. The gene annotation uncovered haplotype-specific differences and confirmed the presence of more than 300 loci, including over 160 protein-coding genes. Combined analysis of the variation and annotation datasets revealed 122 gene loci with coding substitutions of which 97 were non-synonymous. The haplotype (A3-B7-DR15; PGF cell line) designated as the new MHC reference sequence, has been incorporated into the human genome assembly (NCBI35 and subsequent builds), and constitutes the largest single-haplotype sequence of the human genome to date. The extensive variation and annotation data derived from the analysis of seven further haplotypes have been made publicly available and provide a framework and resource for future association studies of all MHC-associated diseases and transplant medicine.
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Horton
authors.forename: Richard
authors.initials: R
authors.lastname: Gibson
authors.forename: Penny
authors.initials: P
authors.lastname: Coggill
authors.forename: Marcos
authors.initials: M
authors.lastname: Miretti
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Allcock
authors.forename: Jeff
authors.initials: J
authors.lastname: Almeida
authors.forename: Simon
authors.initials: S
authors.lastname: Forbes
authors.forename: James G R
authors.initials: JG
authors.lastname: Gilbert
authors.forename: Karen
authors.initials: K
authors.lastname: Halls
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Harrow
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hart
authors.forename: Kevin
authors.initials: K
authors.lastname: Howe
authors.forename: David K
authors.initials: DK
authors.lastname: Jackson
authors.forename: Sophie
authors.initials: S
authors.lastname: Palmer
authors.forename: Anne N
authors.initials: AN
authors.lastname: Roberts
authors.forename: Sarah
authors.initials: S
authors.lastname: Sims
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Stewart
authors.forename: James A
authors.initials: JA
authors.lastname: Traherne
authors.forename: Steve
authors.initials: S
authors.lastname: Trevanion
authors.forename: Laurens
authors.initials: L
authors.lastname: Wilming
authors.forename: Jane
authors.initials: J
authors.lastname: Rogers
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: de Jong
authors.forename: John F
authors.initials: JF
authors.lastname: Elliott
authors.forename: Stephen
authors.initials: S
authors.lastname: Sawcer
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: John
authors.initials: J
authors.lastname: Trowsdale
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
mesh_terms: D019295:Computational Biology / Q000379:methods / Q000639:trends; D030541:Databases, Genetic; D014644:Genetic Variation / Q000276:immunology*; D015894:Genome, Human; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D009626:Terminology as Topic
chemical_list: D006680:HLA Antigens