Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC

Tariq Ahmad, Matt Neville, Sara E. Marshall, Alessandro Armuzzi, Kim Mulcahy-Hawes, Jonathan Crawshaw, Hiroe Sato, Khoon-Lin Ling, Martin Barnardo, Sue Goldthorpe, Robert Walton, Mike Bunce, Derek P. Jewell, Ken I. Welsh

    Research output: Contribution to journalArticlepeer-review

    129 Citations (Scopus)


    Detailed knowledge of linkage disequilibrium (LD) is regarded as a prerequisite for population-based disease gene mapping. Variable patterns across the human genome are now recognized, both between regions and populations. Here, we demonstrate that LD may also vary within a genomic region in a haplotype-specific manner. In 864 Caucasian unrelated individuals, we describe haplotype-specific LD patterns across the human MHC by the construction of gene-specific allelic haplotypes at 25 loci between HLA-A and Tapasin. Strong and extensive LD is found across both common and rare haplotypes, suggesting that haplotype structure is influenced by factors other than genetic drift, including both selection and differential haplotype recombination. Knowledge of haplotype-specific LD in the HLA may explain the apparent discrepant data from previous studies of global LD, help delineate key areas in mapping HLA-associated diseases and, together with recombination data, provide valuable information about a population's demographic history and the selective pressures operating on it.
    Original languageEnglish
    Pages (from-to)647-656
    Number of pages10
    JournalHuman Molecular Genetics
    Issue number6
    Publication statusPublished - Mar 2003


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