Molecular analysis of the beta-globin gene cluster in the niokholo mandenka population reveals a recent origin of the beta(S) senegal mutation

A large and ethnically well-defined Mandenka sample from eastern Senegal wa s analyzed for the polymorphism of the beta -globin gene cluster on chromos ome 11. Five RFLP sites of the 5' region were investigated in 193 individua ls revealing the presence of 10 different haplotypes. The frequency of the sickle-cell anemia causing mutation (beta (S))in the Mandenka estimated fro m this sample is 11.7%. This mutation was found strictly associated with th e single Senegal haplotype. Approximately 600 bp of the upstream region of the beta -globin gene were sequenced for a subset of 94 chromosomes, showin g the presence of four transversions, five transitions, and a composite mic rosatellite 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 variabl e initial frequencies of the Senegal haplotype) were used to estimate the a ge 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-c >5,000) and stationa ry 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 gr eat diversity found on beta (A) chromosomes.