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

  1. Author:
    de Bakker, P. I. W.
    McVean, G.
    Sabeti, P. C.
    Miretti, M. M.
    Green, T.
    Marchini, J.
    Ke, X. Y.
    Monsuur, A. J.
    Whittaker, P.
    Delgado, M.
    Morrison, J.
    Richardson, A.
    Walsh, E. C.
    Gao, X. J.
    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.

  2. Author Address

    Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. Univ Oxford, Dept Stat, Oxford OX1 2JD, England. Wellcome Trust Sanger Inst, Hinxton, England. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. Univ Utrecht, Med Ctr, Dept Med Genet, Complex Genet Sect, NL-3508 TC Utrecht, Netherlands. SAIC Frederick Inc, Lab Genom Divers, Frederick, MD USA. NCI, Frederick, MD 21701 USA. Illumina Inc, San Diego, CA USA. Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27706 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Cambridge, Inst Med Res, Wellcome Trust Diabet & Inflammat Lab, Juventil Diabet Res Fdn, Cambridge CB2 1TN, England. Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England. Imperial Coll Sch Med, London, England. Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Rioux, JD, Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;rioux@broad.mit.edu
    1. Year: 2006
    2. Date: Oct
  2. Journal: Nature Genetics
    1. 38
    2. 10
    3. Pages: 1166-1172
  4. Type of Article: Article
  5. ISSN: 1061-4036
  1. 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(1). Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC2,3. 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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  2. DOI: 10.1038/ng1885
  3. View record in Web of Science®
  4. WOS: 000241251100016

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