Diversity of Lactase Persistence Alleles in Ethiopia: Signature of a Soft Selective Sweep |
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Authors: | Bryony?L Jones Tamiru?O Raga Anke Liebert Pawel Zmarz Endashaw Bekele E?Thomas Danielsen Anders?Krüger Olsen Neil Bradman Jesper?T Troelsen Dallas?M Swallow |
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Institution: | 1.Research Department of Genetics Evolution and Environment, University College London, Darwin Building, London WC1E 6BT, UK;2.Department of Biology, University of Addis Ababa, PO Box 32597, Ethiopia;3.Department of Science, Systems and Models, Roskilde University, 4000 Roskilde, Denmark;4.Henry Stewart Group, 28/30 Little Russell Street, London WC1A 2HN, UK |
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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. |
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