Diversity of Lactase Persistence Alleles in Ethiopia

Signature of a Soft Selective Sweep

BL Jones, TO Raga, Anke Liebert, Anders Krüger Olsen, Erik Thomas Danielsen, E Bekele, Jesper Troelsen, N Bradman, Dallas M Swallow

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other alleles (−13907∗G, rs41525747; −13915∗G, rs41380347; −14010∗C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP, −14009T>G (ss 820486563), is significantly associated with lactose-digester status, and in vitro functional tests confirm that the −14009∗G allele also increases expression of an LCT promoter construct. The derived alleles in the LCT enhancer region are spread through several ethnic groups, and we report a greater genetic diversity in lactose digesters than in nondigesters. By examining flanking markers to control for the effects of mutation and demography, we further describe, from empirical evidence, the signature of a soft selective sweep.
    OriginalsprogEngelsk
    TidsskriftAmerican Journal of Human Genetics
    Vol/bind93
    Udgave nummer3
    Sider (fra-til)538-544
    Antal sider7
    ISSN0002-9297
    DOI
    StatusUdgivet - 2013

    Citer dette

    Jones, BL., Raga, TO., Liebert, A., Olsen, A. K., Danielsen, E. T., Bekele, E., ... Swallow, D. M. (2013). Diversity of Lactase Persistence Alleles in Ethiopia: Signature of a Soft Selective Sweep. American Journal of Human Genetics, 93(3), 538-544. https://doi.org/10.1016/j.ajhg.2013.07.008
    Jones, BL ; Raga, TO ; Liebert, Anke ; Olsen, Anders Krüger ; Danielsen, Erik Thomas ; Bekele, E ; Troelsen, Jesper ; Bradman, N ; Swallow, Dallas M. / Diversity of Lactase Persistence Alleles in Ethiopia : Signature of a Soft Selective Sweep. I: American Journal of Human Genetics. 2013 ; Bind 93, Nr. 3. s. 538-544.
    @article{4578e14161df4068921befd2e883f432,
    title = "Diversity of Lactase Persistence Alleles in Ethiopia: Signature of a Soft Selective Sweep",
    abstract = "The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other alleles (−13907∗G, rs41525747; −13915∗G, rs41380347; −14010∗C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP, −14009T>G (ss 820486563), is significantly associated with lactose-digester status, and in vitro functional tests confirm that the −14009∗G allele also increases expression of an LCT promoter construct. The derived alleles in the LCT enhancer region are spread through several ethnic groups, and we report a greater genetic diversity in lactose digesters than in nondigesters. By examining flanking markers to control for the effects of mutation and demography, we further describe, from empirical evidence, the signature of a soft selective sweep.",
    author = "BL Jones and TO Raga and Anke Liebert and Olsen, {Anders Kr{\"u}ger} and Danielsen, {Erik Thomas} and E Bekele and Jesper Troelsen and N Bradman and Swallow, {Dallas M}",
    year = "2013",
    doi = "10.1016/j.ajhg.2013.07.008",
    language = "English",
    volume = "93",
    pages = "538--544",
    journal = "American Journal of Human Genetics",
    issn = "0002-9297",
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    Jones, BL, Raga, TO, Liebert, A, Olsen, AK, Danielsen, ET, Bekele, E, Troelsen, J, Bradman, N & Swallow, DM 2013, 'Diversity of Lactase Persistence Alleles in Ethiopia: Signature of a Soft Selective Sweep', American Journal of Human Genetics, bind 93, nr. 3, s. 538-544. https://doi.org/10.1016/j.ajhg.2013.07.008

    Diversity of Lactase Persistence Alleles in Ethiopia : Signature of a Soft Selective Sweep. / Jones, BL; Raga, TO; Liebert, Anke; Olsen, Anders Krüger ; Danielsen, Erik Thomas; Bekele, E; Troelsen, Jesper; Bradman, N; Swallow, Dallas M.

    I: American Journal of Human Genetics, Bind 93, Nr. 3, 2013, s. 538-544.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Diversity of Lactase Persistence Alleles in Ethiopia

    T2 - Signature of a Soft Selective Sweep

    AU - Jones, BL

    AU - Raga, TO

    AU - Liebert, Anke

    AU - Olsen, Anders Krüger

    AU - Danielsen, Erik Thomas

    AU - Bekele, E

    AU - Troelsen, Jesper

    AU - Bradman, N

    AU - Swallow, Dallas M

    PY - 2013

    Y1 - 2013

    N2 - The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other alleles (−13907∗G, rs41525747; −13915∗G, rs41380347; −14010∗C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP, −14009T>G (ss 820486563), is significantly associated with lactose-digester status, and in vitro functional tests confirm that the −14009∗G allele also increases expression of an LCT promoter construct. The derived alleles in the LCT enhancer region are spread through several ethnic groups, and we report a greater genetic diversity in lactose digesters than in nondigesters. By examining flanking markers to control for the effects of mutation and demography, we further describe, from empirical evidence, the signature of a soft selective sweep.

    AB - The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other alleles (−13907∗G, rs41525747; −13915∗G, rs41380347; −14010∗C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP, −14009T>G (ss 820486563), is significantly associated with lactose-digester status, and in vitro functional tests confirm that the −14009∗G allele also increases expression of an LCT promoter construct. The derived alleles in the LCT enhancer region are spread through several ethnic groups, and we report a greater genetic diversity in lactose digesters than in nondigesters. By examining flanking markers to control for the effects of mutation and demography, we further describe, from empirical evidence, the signature of a soft selective sweep.

    U2 - 10.1016/j.ajhg.2013.07.008

    DO - 10.1016/j.ajhg.2013.07.008

    M3 - Journal article

    VL - 93

    SP - 538

    EP - 544

    JO - American Journal of Human Genetics

    JF - American Journal of Human Genetics

    SN - 0002-9297

    IS - 3

    ER -