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.
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We thank Steve Jones, Tudor Parfitt, H. Babiker, Pat Smith, David Zeitlyn, Matthew Forka and Elizabeth Caldwell for help with collection of samples, and Ranji Araseratnam, Abigail Jones and many undergraduate students, in particular Naser Ansari Pour, Fiona Pring and Rhonda Sturley for preparing the DNA and/or testing for LCT markers. C. J. E. Ingram was funded by a BBSRC CASE studentship.
Author information Authors and AffiliationsDepartment of Biology, Galton Laboratory, University College London, Wolfson House, 4 Stephenson Way, London, NW1 2HE, UK
Catherine J. E. Ingram, Mohamed F. Elamin, Charlotte A. Mulcare & Dallas M. Swallow
TCGA, Department of Biology, University College London, London, NW1 2HE, UK
Charlotte A. Mulcare, Michael E. Weale, Ayele Tarekegn, Mark G. Thomas & Neil Bradman
Institute for Genome Sciences and Policy, Duke University, Durham, NC, 27708, USA
Michael E. Weale
Elrazi College of Medical and Health Sciences, P.O. Box 4168, Khartoum, Sudan
Mohamed F. Elamin & Farouk M. Elamin
Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia
Ayele Tarekegn, Tamiru Oljira Raga & Endashaw Bekele
Correspondence to Dallas M. Swallow.
Electronic supplementary material About this article Cite this articleIngram, C.J.E., Elamin, M.F., Mulcare, C.A. et al. A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?. Hum Genet 120, 779–788 (2007). https://doi.org/10.1007/s00439-006-0291-1
Received: 20 September 2006
Accepted: 25 October 2006
Published: 21 November 2006
Issue Date: February 2007
DOI: https://doi.org/10.1007/s00439-006-0291-1
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