Scientific article

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

Published inAmerican journal of human genetics, vol. 70, no. 1, p. 207-223
Publication date2002

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.

  • Sickle Cell/genetics Anemia
  • Human Chromosomes
  • Computer Simulation
  • DNA Mutational Analysis
  • Ethnic Groups/genetics
  • Molecular Evolution
  • Gene Frequency/genetics
  • Genetic Variation/genetics
  • Globins/genetics
  • Haplotypes/genetics
  • Humans
  • Likelihood Functions
  • Microsatellite Repeats/genetics
  • Genetic Models
  • Monte Carlo Method
  • Multigene Family/genetics
  • Mutation/genetics
  • Restriction Fragment Length Polymorphism
  • Senegal/ethnology
  • Time Factors
Citation (ISO format)
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
Main files (1)
Article (Accepted version)
ISSN of the journal0002-9297

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