title: Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta(S) Senegal mutation.
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.
authors.affiliation: Genetics and Biometry Laboratory, Department of Anthropology and Ecology, University of Geneva, Geneva, Switzerland. mathias.currat@anthro.unige.ch
authors.forename: Mathias
authors.initials: M
authors.lastname: Currat
authors.forename: Guy
authors.initials: G
authors.lastname: Trabuchet
authors.forename: David
authors.initials: D
authors.lastname: Rees
authors.forename: Pascale
authors.initials: P
authors.lastname: Perrin
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: Harding
authors.forename: John B
authors.initials: JB
authors.lastname: Clegg
authors.forename: André
authors.initials: A
authors.lastname: Langaney
authors.forename: Laurent
authors.initials: L
authors.lastname: Excoffier
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D019143:Evolution, Molecular; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005914:Globins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016013:Likelihood Functions; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D009010:Monte Carlo Method; D005810:Multigene Family / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012675:Senegal / Q000208:ethnology; D013997:Time Factors
chemical_list: D005914:Globins