title: Linkage disequilibrium and haplotype blocks in the MHC vary in an HLA haplotype specific manner assessed mainly by DRB1*03 and DRB1*04 haplotypes.
abstract: First generation linkage disequilibrium (LD) and haplotype maps of the human major histocompatibility complex (MHC) have been generated in order to aid the unraveling of the numerous disease predisposing genes in this region by offering a first set of haplotype tagSNPs. Several parameters, like the population studied, the marker map used, the density of polymorphisms and the applied algorithm, are influencing the appearance of haplotype blocks and selection of tags. The MHC comprises a limited number of ancestral, conserved haplotypes. We address the impact of the underlying HLA haplotypes on the LD patterns, haplotype blocks and tag selection throughout the entire extended MHC (xMHC) by studying DR-DQ haplotypes, mainly those carrying DRB1*03 and DRB1*04 alleles. We observed significantly different degree and extent of LD calculated on different HLA backgrounds, as well as variation in the size and boundaries of the defined haplotype and tags selected. Our results demonstrate that the underlying ancestral HLA haplotypic architecture is yet another parameter to take into consideration when constructing LD maps of the xMHC. This may be essential for mapping of disease susceptibility genes since many diseases are associated with and map on particular HLA haplotypes.
authors.affiliation: Institute of Medical Genetics, Faculty Division, Ullevål University Hospital, University of Oslo, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Blomhoff
authors.forename: M
authors.initials: M
authors.lastname: Olsson
authors.forename: S
authors.initials: S
authors.lastname: Johansson
authors.forename: H E
authors.initials: HE
authors.lastname: Akselsen
authors.forename: F
authors.initials: F
authors.lastname: Pociot
authors.forename: J
authors.initials: J
authors.lastname: Nerup
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: A
authors.initials: A
authors.lastname: Cambon-Thomsen
authors.forename: E
authors.initials: E
authors.lastname: Thorsby
authors.forename: D E
authors.initials: DE
authors.lastname: Undlien
authors.forename: B A
authors.initials: BA
authors.lastname: Lie
mesh_terms: D002874:Chromosome Mapping; D005819:Genetic Markers; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens