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

By P. D. Bakker, G. McVean, Pardis C Sabeti, M. Miretti, Todd Green, Jonathan Marchini, X. Ke, Alienke J. Monsuur, P. Whittaker, Marcos Delgado and 19 more. Nature Genetics, 2006

810 citations recorded by the source corpus.

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.

Subfields: Genetics, Immunology

View Paper: https://www.semanticscholar.org/paper/0c727f543b0cdd28af6027196a6d2964d004e729

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Citations in the corpus

Novel celiac disease genetic determinants related to the immune response (2008, methodology): “; we also included five SNPs to identify HLA-DQ2 or HLA-DQ8 statu”
The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits (2012, background): “A detailed description of how SNPs were selected in each of these categories can be found in the Supplementary Text [21–25].”
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci (2009, background): “The known MHC class I and class II associations were detected in the replication samples: rs3135388 is the surrogate marker for the HLA DRB1a1501 risk allele and rs2523393 is a surrogate marker for the HLA Ba4402 allele ( Table 2 and Online Methods”
HLA variation and disease (2018, background): “Diabetogenic T cells from nonobese diabetic (NOD) mice recognize an insu lin Bchain peptide, which is bound to the MHC class II IA g7 molecule in a lowaffinity register 23 , thus demon strating the potential importance of the peptide bind ing register.”
Major Histocompatibility Complex Genomics and Human Disease (2013, neutral): “SNP typing was introduced to replace classical typing, although if applied to the MHC, as it was in GWAS screens, it had some limitations (25, 78, 86).”
Genome-wide association study identifies susceptibility loci for IgA nephropathy (2011, background): “To better delineate the risk associated with the MHC region and detect potential functional variants, we imputed classical HLA alleles in the discovery cohor”
De novo assembly and genotyping of variants using colored de Bruijn graphs (2012, background): “Both individuals have classical HLA alleles typed in a previous projec”
Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications (2014, result): “Three of the four alleles could be uniquely typed at six-digit resolution ( Supplementary Table 4 ), better than was achieved by previous laboratory typing 39 .”
Variance component model to account for sample structure in genome-wide association studies (2010, positive): “We re-estimated the variance parameters by conditioning on the 57 and 134 SNPs within the extended human MHC regio”
Imputing Amino Acid Polymorphisms in Human Leukocyte Antigens (2013, methodology): “Initially, our group devised a simple approach using selected tag SNPs that are in strong LD with classical HLA alleles [8,10].”
HLA-A★3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans (2011, background): “Therefore, we focused on this locus as a predictor of response through high-resolution, sequence-based HLA-A typing, which confirmed the absolute correlation (r(2) = 1) between rs1061235 and HLA-A*3101 that had been observed previously.(22) No other classic HLA-A alleles reached nominal significance”