A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.
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.
de Bakker
Paul I W
PI
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA.
McVean
Gil
G
Sabeti
Pardis C
PC
Miretti
Marcos M
MM
Green
Todd
T
Marchini
Jonathan
J
Ke
Xiayi
X
Monsuur
Alienke J
AJ
Whittaker
Pamela
P
Delgado
Marcos
M
Morrison
Jonathan
J
Richardson
Angela
A
Walsh
Emily C
EC
Gao
Xiaojiang
X
Galver
Luana
L
Hart
John
J
Hafler
David A
DA
Pericak-Vance
Margaret
M
Todd
John A
JA
Daly
Mark J
MJ
Trowsdale
John
J
Wijmenga
Cisca
C
Vyse
Tim J
TJ
Beck
Stephan
S
Murray
Sarah Shaw
SS
Carrington
Mary
M
Gregory
Simon
S
Deloukas
Panos
P
Rioux
John D
JD
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
D006680:HLA Antigens; D006649:Histocompatibility Antigens