Human Genetics

, Volume 120, Issue 6, pp 779–788 | Cite as

A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?

  • Catherine J. E. Ingram
  • Mohamed F. Elamin
  • Charlotte A. Mulcare
  • Michael E. Weale
  • Ayele Tarekegn
  • Tamiru Oljira Raga
  • Endashaw Bekele
  • Farouk M. Elamin
  • Mark G. Thomas
  • Neil Bradman
  • Dallas M. Swallow
Original Investigation

Abstract

Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (C-13910T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). The -13910*T allele occurs at very high frequency in northern Europeans as part of a very long haplotype (known as A), and promotes binding of the transcription factor Oct-1. However, -13910*T is at very low frequency in many African milk drinking pastoralist groups where lactase persistence phenotype has been reported at high frequency. We report here for the first time, a cohort study of lactose digester and non-digester Sudanese volunteers and show there is no association of -13910*T or the A haplotype with lactase persistence. We support this finding with new genotype/phenotype frequency comparisons in pastoralist groups of eastern African and Middle Eastern origin. Resequencing revealed three new SNPs in close proximity to -13910*T, two of which are within the Oct-1 binding site. The most frequent of these (-13915*G) is associated with lactose tolerance in the cohort study, providing evidence for a cis-acting effect. Despite its location, -13915*G abolishes, rather than enhances Oct-1 binding, indicating that this particular interaction is unlikely to be involved in lactase persistence. This study reveals the complexity of this phenotypic polymorphism and highlights the limitations of C-13910T as a diagnostic test for lactase persistence status, at least for people with non-European ancestry.

Supplementary material

439_2006_291_MOESM1_ESM.doc (46 kb)
Supplementary material

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Catherine J. E. Ingram
    • 1
  • Mohamed F. Elamin
    • 1
    • 4
  • Charlotte A. Mulcare
    • 1
    • 2
  • Michael E. Weale
    • 2
    • 3
  • Ayele Tarekegn
    • 2
    • 5
  • Tamiru Oljira Raga
    • 5
  • Endashaw Bekele
    • 5
  • Farouk M. Elamin
    • 4
  • Mark G. Thomas
    • 2
  • Neil Bradman
    • 2
  • Dallas M. Swallow
    • 1
  1. 1.Department of Biology, Galton LaboratoryUniversity College LondonLondonUK
  2. 2.TCGA, Department of BiologyUniversity College LondonLondonUK
  3. 3.Institute for Genome Sciences and PolicyDuke UniversityDurhamUSA
  4. 4.Elrazi College of Medical and Health SciencesKhartoumSudan
  5. 5.Addis Ababa UniversityAddis AbabaEthiopia

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