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Cited by 766Genetic Associations and EpidemiologyForensic and Genetic ResearchGenetic Mapping and Diversity in Plants and Animals

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

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de Bakker, Paul I W, McVean, Gil, Sabeti, Pardis C, Miretti, Marcos M, Green, Todd, Marchini, Jonathan, Ke, Xiayi, Monsuur, Alienke J +21 more·2006·Nature Genetics
DOI 10.1038/ng1885PMC PMC2670196
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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.

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  • Compilation of large reference populations with both serological and genotyping data on MHC variation has made imputation of classical alleles possible from standard SNP array data to single amino acid resolution.

    “Over the last several years, the compilation of large reference populations with both serological and genotyping data on MHC variation has made imputation of classical alleles possible from standard SNP array data to single amino acid resolution.48, 49”

    From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [48]

    The Abstract (page not specified) reports that SNP tags captured many common classical HLA alleles, and Methods > Empirical validation (page not specified) describes testing how well those tags predicted patients’ HLA alleles. The paper does not establish imputation from standard SNP-array data to single-amino-acid resolution; Methods > HLA typing describes PCR-based typing rather than serological typing. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 33

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Authors
de Bakker, P. I. W., McVean, G., Sabeti, P. C., Miretti, M. M., Green, T., Marchini, J., Ke, X., Monsuur, A. J., Whittaker, P., Delgado, M., Morrison, J., Richardson, A., Walsh, E. C., Gao, X., Galver, L., Hart, J., Hafler, D. A., Pericak-Vance, M., Todd, J. A., Daly, M. J., Trowsdale, J., Wijmenga, C., Vyse, T. J., Beck, S., Murray, S. S., Carrington, M., Gregory, S., Deloukas, P., & Rioux, J. D.
Affiliations
  • University of Oxford (GB)
  • Broad Institute (US)
  • Wellcome Sanger Institute (GB)
  • Centre for Human Genetics (GB)
  • University Medical Center Utrecht (NL)
  • National Cancer Institute (US)
  • Illumina (United States) (US)
  • Duke Medical Center (US)
  • University of Cambridge (GB)
  • Addenbrooke's Hospital (GB)
  • Imperial College London (GB)
Corresponding author
Rioux, John D
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2006-09-24
Volume
38
Issue
10
Pages
1166-1172
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng1885
PMC
PMC2670196
OpenAlex
W2152381343
Cited by
766
References
0
Citations by year
2026: 8 · 2025: 18 · 2024: 17 · 2023: 22 · 2022: 19 · 2021: 25 · 2020: 30 · 2019: 28 · 2018: 40 · 2017: 38 · 2016: 36 · 2015: 55 · 2014: 55 · 2013: 52 · 2012: 58
FWCI
26.58
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
Funders
  • Wellcome Trust (077011)
  • National Institutes of Health (n01co12400-79-0-22)
  • National Cancer Institute (N01CO12400, N01-CO-012400)
  • National Institute of Allergy and Infectious Diseases (U19AI050864)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
HLA, major histocompatibility complex, HapMap, linkage disequilibrium, tag SNPs, HLA class I, HLA class II, HLA polymorphism, disease association studies, insertion/deletion polymorphism, population variation
MeSH terms
Genetics, Medical, Haplotypes, Histocompatibility Antigens, HLA Antigens, Humans, Polymorphism, Genetic, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Racial Groups

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