title: A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.
abstract: The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
authors.affiliation: Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Gil
authors.initials: G
authors.lastname: McVean
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
authors.forename: Marcos M
authors.initials: MM
authors.lastname: Miretti
authors.forename: Todd
authors.initials: T
authors.lastname: Green
authors.forename: Jonathan
authors.initials: J
authors.lastname: Marchini
authors.forename: Xiayi
authors.initials: X
authors.lastname: Ke
authors.forename: Alienke J
authors.initials: AJ
authors.lastname: Monsuur
authors.forename: Pamela
authors.initials: P
authors.lastname: Whittaker
authors.forename: Marcos
authors.initials: M
authors.lastname: Delgado
authors.forename: Jonathan
authors.initials: J
authors.lastname: Morrison
authors.forename: Angela
authors.initials: A
authors.lastname: Richardson
authors.forename: Emily C
authors.initials: EC
authors.lastname: Walsh
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Luana
authors.initials: L
authors.lastname: Galver
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Margaret
authors.initials: M
authors.lastname: Pericak-Vance
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: John
authors.initials: J
authors.lastname: Trowsdale
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
authors.forename: Sarah Shaw
authors.initials: SS
authors.lastname: Murray
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Simon
authors.initials: S
authors.lastname: Gregory
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
mesh_terms: D020022:Genetic Predisposition to Disease; D005826:Genetics, Medical; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006649:Histocompatibility Antigens / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics
chemical_list: D006680:HLA Antigens; D006649:Histocompatibility Antigens