A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC

Paul I W De Bakker, Gil McVean, Pardis C. Sabeti, Marcos M. Miretti, Todd Green, Jonathan Marchini, Xiayi Ke, Alienke J. Monsuur, Pamela Whittaker, Marcos Delgado, Jonathan Morrison, Angela Richardson, Emily C. Walsh, Xiaojiang Gao, Luana Galver, John Hart, David A. Hafler, Margaret A Pericak-Vance, John A. Todd, Mark J. Daly & 9 others John Trowsdale, Cisca Wijmenga, Tim J. Vyse, Stephan Beck, Sarah Shaw Murray, Mary Carrington, Simon Gregory, Panos Deloukas, John D. Rioux

Research output: Contribution to journalArticle

515 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1166-1172
Number of pages7
JournalNature Genetics
Volume38
Issue number10
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Fingerprint

Major Histocompatibility Complex
Haplotypes
Single Nucleotide Polymorphism
Linkage Disequilibrium
Genes
Histocompatibility Testing
MHC Class II Genes
Graft Rejection
Autoimmune Diseases
Communicable Diseases
Population
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

De Bakker, P. I. W., McVean, G., Sabeti, P. C., Miretti, M. M., Green, T., Marchini, J., ... Rioux, J. D. (2006). A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nature Genetics, 38(10), 1166-1172. https://doi.org/10.1038/ng1885

A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. / De Bakker, Paul I W; McVean, Gil; Sabeti, Pardis C.; Miretti, Marcos M.; Green, Todd; Marchini, Jonathan; Ke, Xiayi; Monsuur, Alienke J.; Whittaker, Pamela; Delgado, Marcos; Morrison, Jonathan; Richardson, Angela; Walsh, Emily C.; Gao, Xiaojiang; Galver, Luana; Hart, John; Hafler, David A.; Pericak-Vance, Margaret A; Todd, John A.; Daly, Mark J.; Trowsdale, John; Wijmenga, Cisca; Vyse, Tim J.; Beck, Stephan; Murray, Sarah Shaw; Carrington, Mary; Gregory, Simon; Deloukas, Panos; Rioux, John D.

In: Nature Genetics, Vol. 38, No. 10, 01.10.2006, p. 1166-1172.

Research output: Contribution to journalArticle

De Bakker, PIW, McVean, G, Sabeti, PC, Miretti, MM, Green, T, Marchini, J, Ke, X, Monsuur, AJ, Whittaker, P, Delgado, M, Morrison, J, Richardson, A, Walsh, EC, Gao, X, Galver, L, Hart, J, Hafler, DA, Pericak-Vance, MA, Todd, JA, Daly, MJ, Trowsdale, J, Wijmenga, C, Vyse, TJ, Beck, S, Murray, SS, Carrington, M, Gregory, S, Deloukas, P & Rioux, JD 2006, 'A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC', Nature Genetics, vol. 38, no. 10, pp. 1166-1172. https://doi.org/10.1038/ng1885
De Bakker PIW, McVean G, Sabeti PC, Miretti MM, Green T, Marchini J et al. A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nature Genetics. 2006 Oct 1;38(10):1166-1172. https://doi.org/10.1038/ng1885
De Bakker, Paul I W ; McVean, Gil ; Sabeti, Pardis C. ; Miretti, Marcos M. ; Green, Todd ; Marchini, Jonathan ; Ke, Xiayi ; Monsuur, Alienke J. ; Whittaker, Pamela ; Delgado, Marcos ; Morrison, Jonathan ; Richardson, Angela ; Walsh, Emily C. ; Gao, Xiaojiang ; Galver, Luana ; Hart, John ; Hafler, David A. ; Pericak-Vance, Margaret A ; Todd, John A. ; Daly, Mark J. ; Trowsdale, John ; Wijmenga, Cisca ; Vyse, Tim J. ; Beck, Stephan ; Murray, Sarah Shaw ; Carrington, Mary ; Gregory, Simon ; Deloukas, Panos ; Rioux, John D. / A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. In: Nature Genetics. 2006 ; Vol. 38, No. 10. pp. 1166-1172.
@article{ce29de1db5ad4869bf5f8e40775c4a11,
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.",
author = "{De Bakker}, {Paul I W} and Gil McVean and Sabeti, {Pardis C.} and Miretti, {Marcos M.} and Todd Green and Jonathan Marchini and Xiayi Ke and Monsuur, {Alienke J.} and Pamela Whittaker and Marcos Delgado and Jonathan Morrison and Angela Richardson and Walsh, {Emily C.} and Xiaojiang Gao and Luana Galver and John Hart and Hafler, {David A.} and Pericak-Vance, {Margaret A} and Todd, {John A.} and Daly, {Mark J.} and John Trowsdale and Cisca Wijmenga and Vyse, {Tim J.} and Stephan Beck and Murray, {Sarah Shaw} and Mary Carrington and Simon Gregory and Panos Deloukas and Rioux, {John D.}",
year = "2006",
month = "10",
day = "1",
doi = "10.1038/ng1885",
language = "English",
volume = "38",
pages = "1166--1172",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC

AU - De Bakker, Paul I W

AU - McVean, Gil

AU - Sabeti, Pardis C.

AU - Miretti, Marcos M.

AU - Green, Todd

AU - Marchini, Jonathan

AU - Ke, Xiayi

AU - Monsuur, Alienke J.

AU - Whittaker, Pamela

AU - Delgado, Marcos

AU - Morrison, Jonathan

AU - Richardson, Angela

AU - Walsh, Emily C.

AU - Gao, Xiaojiang

AU - Galver, Luana

AU - Hart, John

AU - Hafler, David A.

AU - Pericak-Vance, Margaret A

AU - Todd, John A.

AU - Daly, Mark J.

AU - Trowsdale, John

AU - Wijmenga, Cisca

AU - Vyse, Tim J.

AU - Beck, Stephan

AU - Murray, Sarah Shaw

AU - Carrington, Mary

AU - Gregory, Simon

AU - Deloukas, Panos

AU - Rioux, John D.

PY - 2006/10/1

Y1 - 2006/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33749137515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749137515&partnerID=8YFLogxK

U2 - 10.1038/ng1885

DO - 10.1038/ng1885

M3 - Article

VL - 38

SP - 1166

EP - 1172

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

ER -