A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?
| Autor: | Charlotte A. Mulcare, Tamiru Oljira Raga, Endashaw Bekele, Ayele Tarekegn, Mohamed F. Elamin, Mark G. Thomas, Farouk M. Elamin, Michael E. Weale, Dallas M. Swallow, Neil Bradman, Catherine J. E. Ingram |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Genotype medicine.medical_treatment Population Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Cohort Studies Middle East Lactose Intolerance Gene Frequency Polymorphism (computer science) Sequence Homology Nucleic Acid Ethnicity Genetics medicine Humans education Allele frequency Genetics (clinical) Lactase education.field_of_study Binding Sites Base Sequence Haplotype DNA Introns Lactase persistence Enhancer Elements Genetic Phenotype Haplotypes Africa DNA Probes Octamer Transcription Factor-1 |
| Zdroj: | Human Genetics. 120:779-788 |
| ISSN: | 1432-1203 0340-6717 |
| DOI: | 10.1007/s00439-006-0291-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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