%0 Journal Article %1 currat2002betaglobin %A Currat, M %A Trabuchet, G %A Rees, D %A Perrin, P %A Harding, R M %A Clegg, J B %A Langaney, A %A Excoffier, L %D 2002 %J Am J Hum Genet %K allele_age disease_resistance humans malaria parallel_adaptation selection sicklecell %N 1 %P 207-223 %R 10.1086/338304 %T Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta(S) Senegal mutation %U http://www.ncbi.nlm.nih.gov/pubmed/11741197?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=11 %V 70 %X 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.

@article{currat2002betaglobin, 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.}, added-at = {2011-05-18T22:20:21.000+0200}, author = {Currat, M and Trabuchet, G and Rees, D and Perrin, P and Harding, R M and Clegg, J B and Langaney, A and Excoffier, L}, biburl = {https://www.bibsonomy.org/bibtex/290be246068e9343d391d288ac20acfd5/peter.ralph}, description = {Molecular analysis of the beta-globin gene cluster... [Am J Hum Genet. 2002] - PubMed result}, doi = {10.1086/338304}, interhash = {bc4e2dd710eee9ae15744dc3bed6b42e}, intrahash = {90be246068e9343d391d288ac20acfd5}, journal = {Am J Hum Genet}, keywords = {allele_age disease_resistance humans malaria parallel_adaptation selection sicklecell}, month = jan, number = 1, pages = {207-223}, pmid = {11741197}, timestamp = {2011-05-18T22:20:21.000+0200}, title = {Molecular analysis of the beta-globin gene cluster in the {Niokholo} {Mandenka} population reveals a recent origin of the {beta(S)} {Senegal} mutation}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11741197?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=11}, volume = 70, year = 2002 }