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Linkage disequilibrium and haplotype blocks in the MHC vary in an HLA haplotype specific manner assessed mainly by DRB1*03 and DRB1*04 haplotypes

Genes & Immunity volume 7, pages 130–140 (2006)Cite this article

Abstract

First generation linkage disequilibrium (LD) and haplotype maps of the human major histocompatibility complex (MHC) have been generated in order to aid the unraveling of the numerous disease predisposing genes in this region by offering a first set of haplotype tagSNPs. Several parameters, like the population studied, the marker map used, the density of polymorphisms and the applied algorithm, are influencing the appearance of haplotype blocks and selection of tags. The MHC comprises a limited number of ancestral, conserved haplotypes. We address the impact of the underlying HLA haplotypes on the LD patterns, haplotype blocks and tag selection throughout the entire extended MHC (xMHC) by studying DR-DQ haplotypes, mainly those carrying DRB1*03 and DRB1*04 alleles. We observed significantly different degree and extent of LD calculated on different HLA backgrounds, as well as variation in the size and boundaries of the defined haplotype and tags selected. Our results demonstrate that the underlying ancestral HLA haplotypic architecture is yet another parameter to take into consideration when constructing LD maps of the xMHC. This may be essential for mapping of disease susceptibility genes since many diseases are associated with and map on particular HLA haplotypes.

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Acknowledgements

This study was supported by the Juvenile Diabetes Research Foundation International (1-2004-793, 1-2000-514, 1-2000-515), the University of Oslo, The Functional Genomics program (FUGE), the Norwegian Research Council, the Norwegian Diabetes Association, the NovoNordisk Foundation, Eastern Norway Regional Health Authority and the Swedish Foundation for Strategic Research (1999/0211). We thank the Norwegian Study Group for childhood Diabetes, the Danish Study Group of Diabetes in Childhood, the Danish IDDM Epidemiology and Genetics Group, the Swedish Childhood Diabetes Study, the Diabetes Incidence Study in Sweden, the French Network Inserm for IDDM and MS in Atlantic Pyrenees (Dr A Cambon-Thomsen) and the Regional Observatory of health in Aquitaine region (Dr J Doutreix) for the collection of samples used in this study. We also thank Dr K Zhang for making the HapBlock program available for multiallelic markers.

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Author notes

  1. S Johansson

    Present address: Section for Medical Genetics and Molecular Medicine and Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Norway

Authors and Affiliations

  1. Faculty Division Ullevål University Hospital, Institute of Medical Genetics, University of Oslo, Oslo, Norway

    A Blomhoff & D E Undlien

  2. Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway

    A Blomhoff & H E Akselsen

  3. Department of Mathematical Statistics, Chalmers University of Technology, Göteborg, Sweden

    M Olsson

  4. Institute of Immunology, University of Oslo, Oslo, Norway

    S Johansson & E Thorsby

  5. Steno Diabetes Centre, Gentofte, Denmark

    F Pociot & J Nerup

  6. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    I Kockum

  7. Inserm U 558, University Paul Sabatier, Toulouse, France

    A Cambon-Thomsen

  8. Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway

    E Thorsby & B A Lie

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  1. A Blomhoff
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Correspondence to B A Lie.

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Blomhoff, A., Olsson, M., Johansson, S. et al. Linkage disequilibrium and haplotype blocks in the MHC vary in an HLA haplotype specific manner assessed mainly by DRB1*03 and DRB1*04 haplotypes. Genes Immun 7, 130–140 (2006). https://doi.org/10.1038/sj.gene.6364272

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