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 journalArticle

    112 Citations (Scopus)

    Abstract

    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
    Volume12
    Issue number6
    Publication statusPublished - Mar 2003

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    Linkage Disequilibrium
    Medical Genetics
    Haplotypes
    Genetic Recombination
    Population
    Genetic Drift
    HLA-A Antigens
    Chromosome Mapping
    Human Genome
    Demography
    Genes

    Cite this

    Ahmad, T., Neville, M., Marshall, S. E., Armuzzi, A., Mulcahy-Hawes, K., Crawshaw, J., ... Welsh, K. I. (2003). Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC. Human Molecular Genetics, 12(6), 647-656.
    Ahmad, Tariq ; Neville, Matt ; Marshall, Sara E. ; Armuzzi, Alessandro ; Mulcahy-Hawes, Kim ; Crawshaw, Jonathan ; Sato, Hiroe ; Ling, Khoon-Lin ; Barnardo, Martin ; Goldthorpe, Sue ; Walton, Robert ; Bunce, Mike ; Jewell, Derek P. ; Welsh, Ken I. / Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC. In: Human Molecular Genetics. 2003 ; Vol. 12, No. 6. pp. 647-656.
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    abstract = "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.",
    author = "Tariq Ahmad and Matt Neville and Marshall, {Sara E.} and Alessandro Armuzzi and Kim Mulcahy-Hawes and Jonathan Crawshaw and Hiroe Sato and Khoon-Lin Ling and Martin Barnardo and Sue Goldthorpe and Robert Walton and Mike Bunce and Jewell, {Derek P.} and Welsh, {Ken I.}",
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    Ahmad, T, Neville, M, Marshall, SE, Armuzzi, A, Mulcahy-Hawes, K, Crawshaw, J, Sato, H, Ling, K-L, Barnardo, M, Goldthorpe, S, Walton, R, Bunce, M, Jewell, DP & Welsh, KI 2003, 'Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC', Human Molecular Genetics, vol. 12, no. 6, pp. 647-656.

    Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC. / Ahmad, Tariq; Neville, Matt; Marshall, Sara E.; Armuzzi, Alessandro; Mulcahy-Hawes, Kim; Crawshaw, Jonathan; Sato, Hiroe; Ling, Khoon-Lin; Barnardo, Martin; Goldthorpe, Sue; Walton, Robert; Bunce, Mike; Jewell, Derek P.; Welsh, Ken I.

    In: Human Molecular Genetics, Vol. 12, No. 6, 03.2003, p. 647-656.

    Research output: Contribution to journalArticle

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    T1 - Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC

    AU - Ahmad, Tariq

    AU - Neville, Matt

    AU - Marshall, Sara E.

    AU - Armuzzi, Alessandro

    AU - Mulcahy-Hawes, Kim

    AU - Crawshaw, Jonathan

    AU - Sato, Hiroe

    AU - Ling, Khoon-Lin

    AU - Barnardo, Martin

    AU - Goldthorpe, Sue

    AU - Walton, Robert

    AU - Bunce, Mike

    AU - Jewell, Derek P.

    AU - Welsh, Ken I.

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    N2 - 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.

    AB - 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.

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    Ahmad T, Neville M, Marshall SE, Armuzzi A, Mulcahy-Hawes K, Crawshaw J et al. Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC. Human Molecular Genetics. 2003 Mar;12(6):647-656.