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.
authors.affiliation: Research Department of Genetics Evolution and Environment, University College London, Darwin Building, London, UK.
authors.forename: Bryony L
authors.initials: BL
authors.lastname: Jones
authors.forename: Tamiru O
authors.initials: TO
authors.lastname: Raga
authors.forename: Anke
authors.initials: A
authors.lastname: Liebert
authors.forename: Pawel
authors.initials: P
authors.lastname: Zmarz
authors.forename: Endashaw
authors.initials: E
authors.lastname: Bekele
authors.forename: E Thomas
authors.initials: ET
authors.lastname: Danielsen
authors.forename: Anders Krüger
authors.initials: AK
authors.lastname: Olsen
authors.forename: Neil
authors.initials: N
authors.lastname: Bradman
authors.forename: Jesper T
authors.initials: JT
authors.lastname: Troelsen
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Swallow
mesh_terms: D000483:Alleles; D001483:Base Sequence; D018938:Caco-2 Cells; D018797:Cell Cycle Proteins / Q000235:genetics; D015331:Cohort Studies; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005002:Ethiopia; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D043322:Lactase / Q000235:genetics*; D064151:Minichromosome Maintenance Complex Component 6; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D043322:Lactase; C103258:MCM6 protein, human; D064151:Minichromosome Maintenance Complex Component 6