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Patterns of linkage disequilibrium in the MHC region on human chromosome 6p

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Abstract

Single nucleotide polymorphisms (SNPs) in the human genome are thought to be organised into blocks of high internal linkage disequilibrium (LD), separated by intermittent recombination hotspots. Since understanding haplotype structure is critical for an accurate assessment of inter-individual genetic differences, we investigated up to 968 SNPs from a 10-Mb region on chromosome 6p21, including the human major histocompatibility complex (MHC), in five different population samples (45–550 individuals). Regions of well-defined block structure were found to coexist alongside large areas lacking any clear structure; occasional long-range LD was observed in all five samples. The four white populations analysed were remarkably similar in terms of the extend and spatial distribution of local LD. In US African Americans, the distribution of LD was similar to that in the white populations but the observed haplotype diversity was higher. The existence of large regions without any clear block structure renders the systematic and thorough construction of SNP haplotype maps a crucial prerequisite for disease-association studies.

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Acknowledgements

The authors thank physicians and technicians at the Kiel blood bank (headed by J. Neppert) for the recruitment of healthy German individuals, and M. Vatn, Oslo, Norway, and C. Mathew, London, UK, for providing local population samples. We acknowledge the expert technical help of T. Wesse and the entire technical staff of the Mucosal Research Laboratory, Kiel. Thanks are also due to J. Ziegle, L. Wogan and the production genotyping team of Services Development and Delivery of Applied Biosystems, and to A. Collins, Southampton, UK, for providing the LDMAP software. This work was supported by the Deutsche Forschungsgemeinschaft (FOR 423), the European Commission (QLG2-CT-2001-02161), and the German Ministry for Education and Research (Competence Network “Inflammatory Bowel Disease”, German Human Genome Project, National Genome Research Network).

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Authors and Affiliations

  1. Abteilung für Allgemeine Innere Medizin, Universitätsklinikum Schleswig-Holstein, Christian-Albrechts-Universität Kiel, 24105, Kiel, Germany

    Annette Stenzel, W. Andreas Koch, Jochen Hampe & Stefan Schreiber

  2. Institut für Medizinische Informatik und Statistik, Universitätsklinikum Schleswig-Holstein, Christian-Albrechts-Universität Kiel, Brunswiker Strasse 10, 24105, Kiel, Germany

    Timothy Lu & Michael Krawczak

  3. Applied Biosystems, Applera Deutschland, 88662, Überlingen, Germany

    Simone M. Guenther

  4. Applied Biosystems, CA 94404, USA

    Francisco M. De La Vega

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  1. Annette Stenzel
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  2. Timothy Lu
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  3. W. Andreas Koch
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  4. Jochen Hampe
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  5. Simone M. Guenther
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  6. Francisco M. De La Vega
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  7. Michael Krawczak
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  8. Stefan Schreiber
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Corresponding author

Correspondence to Michael Krawczak.

Additional information

Electronic database information: URLs for the data in this article are as follows:

http://www.ncbi.nlm.nih.gov/SNP

http://lgb.unige.ch/arlequin/

http://cedar.genetics.soton.ac.uk/public_html

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Stenzel, A., Lu, T., Koch, W.A. et al. Patterns of linkage disequilibrium in the MHC region on human chromosome 6p. Hum Genet 114, 377–385 (2004). https://doi.org/10.1007/s00439-003-1075-5

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