title: An integrated haplotype map of the human major histocompatibility complex.
abstract: Numerous studies have clearly indicated a role for the major histocompatibility complex (MHC) in susceptibility to autoimmune diseases. Such studies have focused on the genetic variation of a small number of classical human-leukocyte-antigen (HLA) genes in the region. Although these genes represent good candidates, given their immunological roles, linkage disequilibrium (LD) surrounding these genes has made it difficult to rule out neighboring genes, many with immune function, as influencing disease susceptibility. It is likely that a comprehensive analysis of the patterns of LD and variation, by using a high-density map of single-nucleotide polymorphisms (SNPs), would enable a greater understanding of the nature of the observed associations, as well as lead to the identification of causal variation. We present herein an initial analysis of this region, using 201 SNPs, nine classical HLA loci, two TAP genes, and 18 microsatellites. This analysis suggests that LD and variation in the MHC, aside from the classical HLA loci, are essentially no different from those in the rest of the genome. Furthermore, these data show that multi-SNP haplotypes will likely be a valuable means for refining association signals in this region.
authors.affiliation: Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Walsh
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Mather
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.forename: Lisa
authors.initials: L
authors.lastname: Farwell
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Michael
authors.initials: M
authors.lastname: Cullen
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Teodorica L
authors.initials: TL
authors.lastname: Bugawan
authors.forename: Henry
authors.initials: H
authors.lastname: Erlich
authors.forename: Jay
authors.initials: J
authors.lastname: Campbell
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Barrett
authors.forename: Katie
authors.initials: K
authors.lastname: Miller
authors.forename: Glenys
authors.initials: G
authors.lastname: Thomson
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
mesh_terms: D002874:Chromosome Mapping; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008285:Major Histocompatibility Complex; D018895:Microsatellite Repeats
chemical_list: D006680:HLA Antigens