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

• Published in: Nature genetics Vol. 38; no. 10; pp. 1166 - 1172
• Main Authors: 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, 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2006; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Antigens; Autoimmune diseases; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genetics, Medical; Haplotypes; Haplotypes - genetics; Histocompatibility antigens; Histocompatibility Antigens - genetics; HLA Antigens - genetics; HLA histocompatibility antigens; Human Genetics; Human subjects; Humans; Immunology; letter; Major histocompatibility complex; Physiological aspects; Polymorphism; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Racial Groups - genetics; Single nucleotide polymorphisms; Canada; Human; High resolution; Association; Single nucleotide polymorphism; Haplotype
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1885

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 MHC 2 , 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.