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Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta(S) Senegal mutation

Trabuchet, Guy
Rees, David
Perrin, Pascale
Harding, Rosalind M.
Clegg, John B.
Published in American journal of human genetics. 2002, vol. 70, no. 1, p. 207-223
Abstract A large and ethnically well-defined Mandenka sample from eastern Senegal was analyzed for the polymorphism of the beta-globin gene cluster on chromosome 11. Five RFLP sites of the 5' region were investigated in 193 individuals revealing the presence of 10 different haplotypes. The frequency of the sickle-cell anemia causing mutation (beta(S)) in the Mandenka estimated from this sample is 11.7%. This mutation was found strictly associated with the single Senegal haplotype. Approximately 600 bp of the upstream region of the beta-globin gene were sequenced for a subset of 94 chromosomes, showing the presence of four transversions, five transitions, and a composite microsatellite polymorphism. The sequence of 22 beta(S) chromosomes was also identical to the previously defined Senegal haplotype, suggesting that this mutation is very recent. Monte Carlo simulations (allowing for a specific balancing selection model, a logistic growth of the population, and variable initial frequencies of the Senegal haplotype) were used to estimate the age of the beta(S) mutation. Resulting maximum-likelihood estimates are 45-70 generations (1,350-2,100 years) for very different demographic scenarios. Smallest confidence intervals (25-690 generations) are obtained under the hypothesis that the Mandenka population is large (N(e) >5,000) and stationary or that it has undergone a rapid demographic expansion to a current size of >5,000 reproducing individuals, which is quite likely in view of the great diversity found on beta(A) chromosomes.
Keywords Sickle Cell/genetics AnemiaHuman ChromosomesComputer SimulationDNA Mutational AnalysisEthnic Groups/geneticsMolecular EvolutionGene Frequency/geneticsGenetic Variation/geneticsGlobins/geneticsHaplotypes/geneticsHumansLikelihood FunctionsMicrosatellite Repeats/geneticsGenetic ModelsMonte Carlo MethodMultigene Family/geneticsMutation/geneticsRestriction Fragment Length PolymorphismSenegal/ethnologyTime Factors
PMID: 11741197
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Research group Unité d'anthropologie
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CURRAT, Mathias et al. Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta(S) Senegal mutation. In: American journal of human genetics, 2002, vol. 70, n° 1, p. 207-223. doi: 10.1086/338304 https://archive-ouverte.unige.ch/unige:2119

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Deposited on : 2009-06-22

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