The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity

Tine G. K. Jensen, Anke Liebert, Rikke Lewinsky, Dallas M. Swallow, Jørgen Olsen, Jesper Troelsen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    In most people worldwide intestinal lactase expression declines in childhood. In many others, particularly in Europeans, lactase expression persists into adult life. The lactase persistence phenotype is in Europe associated with the -13910*T single nucleotide variant located 13,910 bp upstream the lactase gene in an enhancer region that affects lactase promoter activity. This variant falls in an Oct-1 binding site and shows greater Oct-1 binding than the ancestral variant and increases enhancer activity. Several other variants have been identified very close to the -13910 position, which are associated with lactase persistence in the Middle East and Africa. One of them, the -14010*C, is associated with lactase persistence in Africa. Here we show by deletion analysis that the -14010 position is located in a 144 bp region that reduces the enhancer activity. In transfections the -14010*C allele shows a stronger enhancer effect than the ancestral -14010*G allele. Binding sites for Oct-1 and HNF1α surrounding the -14010 position were identified by gel shift assays, which indicated that -14010*C has greater binding affinity to Oct-1 than -14010*G.
    OriginalsprogEngelsk
    TidsskriftHuman Genetics
    Vol/bind130
    Udgave nummer4
    Sider (fra-til)483-493
    ISSN0340-6717
    DOI
    StatusUdgivet - 31 dec. 2011

    Citer dette

    Jensen, Tine G. K. ; Liebert, Anke ; Lewinsky, Rikke ; Swallow, Dallas M. ; Olsen, Jørgen ; Troelsen, Jesper. / The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity. I: Human Genetics. 2011 ; Bind 130, Nr. 4. s. 483-493.
    @article{dc59c557e15e42b9b3c87f3a49629a73,
    title = "The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity",
    abstract = "In most people worldwide intestinal lactase expression declines in childhood. In many others, particularly in Europeans, lactase expression persists into adult life. The lactase persistence phenotype is in Europe associated with the -13910*T single nucleotide variant located 13,910 bp upstream the lactase gene in an enhancer region that affects lactase promoter activity. This variant falls in an Oct-1 binding site and shows greater Oct-1 binding than the ancestral variant and increases enhancer activity. Several other variants have been identified very close to the -13910 position, which are associated with lactase persistence in the Middle East and Africa. One of them, the -14010*C, is associated with lactase persistence in Africa. Here we show by deletion analysis that the -14010 position is located in a 144 bp region that reduces the enhancer activity. In transfections the -14010*C allele shows a stronger enhancer effect than the ancestral -14010*G allele. Binding sites for Oct-1 and HNF1α surrounding the -14010 position were identified by gel shift assays, which indicated that -14010*C has greater binding affinity to Oct-1 than -14010*G.",
    author = "Jensen, {Tine G. K.} and Anke Liebert and Rikke Lewinsky and Swallow, {Dallas M.} and J{\o}rgen Olsen and Jesper Troelsen",
    year = "2011",
    month = "12",
    day = "31",
    doi = "10.1007/s00439-011-0966-0",
    language = "English",
    volume = "130",
    pages = "483--493",
    journal = "Human Genetics",
    issn = "0340-6717",
    publisher = "Physica-Verlag",
    number = "4",

    }

    The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity. / Jensen, Tine G. K.; Liebert, Anke ; Lewinsky, Rikke ; Swallow, Dallas M. ; Olsen, Jørgen ; Troelsen, Jesper.

    I: Human Genetics, Bind 130, Nr. 4, 31.12.2011, s. 483-493.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity

    AU - Jensen, Tine G. K.

    AU - Liebert, Anke

    AU - Lewinsky, Rikke

    AU - Swallow, Dallas M.

    AU - Olsen, Jørgen

    AU - Troelsen, Jesper

    PY - 2011/12/31

    Y1 - 2011/12/31

    N2 - In most people worldwide intestinal lactase expression declines in childhood. In many others, particularly in Europeans, lactase expression persists into adult life. The lactase persistence phenotype is in Europe associated with the -13910*T single nucleotide variant located 13,910 bp upstream the lactase gene in an enhancer region that affects lactase promoter activity. This variant falls in an Oct-1 binding site and shows greater Oct-1 binding than the ancestral variant and increases enhancer activity. Several other variants have been identified very close to the -13910 position, which are associated with lactase persistence in the Middle East and Africa. One of them, the -14010*C, is associated with lactase persistence in Africa. Here we show by deletion analysis that the -14010 position is located in a 144 bp region that reduces the enhancer activity. In transfections the -14010*C allele shows a stronger enhancer effect than the ancestral -14010*G allele. Binding sites for Oct-1 and HNF1α surrounding the -14010 position were identified by gel shift assays, which indicated that -14010*C has greater binding affinity to Oct-1 than -14010*G.

    AB - In most people worldwide intestinal lactase expression declines in childhood. In many others, particularly in Europeans, lactase expression persists into adult life. The lactase persistence phenotype is in Europe associated with the -13910*T single nucleotide variant located 13,910 bp upstream the lactase gene in an enhancer region that affects lactase promoter activity. This variant falls in an Oct-1 binding site and shows greater Oct-1 binding than the ancestral variant and increases enhancer activity. Several other variants have been identified very close to the -13910 position, which are associated with lactase persistence in the Middle East and Africa. One of them, the -14010*C, is associated with lactase persistence in Africa. Here we show by deletion analysis that the -14010 position is located in a 144 bp region that reduces the enhancer activity. In transfections the -14010*C allele shows a stronger enhancer effect than the ancestral -14010*G allele. Binding sites for Oct-1 and HNF1α surrounding the -14010 position were identified by gel shift assays, which indicated that -14010*C has greater binding affinity to Oct-1 than -14010*G.

    U2 - 10.1007/s00439-011-0966-0

    DO - 10.1007/s00439-011-0966-0

    M3 - Journal article

    VL - 130

    SP - 483

    EP - 493

    JO - Human Genetics

    JF - Human Genetics

    SN - 0340-6717

    IS - 4

    ER -