Molecular analysis of the β-globin gene cluster in the niokholo mandenka population reveals a recent origin of the βS senegal mutation
Molecular analysis of the β-globin gene cluster in the niokholo mandenka population reveals a recent origin of the βS senegal mutation
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DOI：
10.1086/338304
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发表时间：
2002-01-01
影响因子：
9.8
通讯作者：
Excoffier, L
中科院分区：
文献类型：
--
作者：
Currat, M;Trabuchet, G;Excoffier, L
分析了塞内加尔东部曼登卡人11号染色体上β-珠蛋白基因簇的多态性。对193名个体的5‘区5个RFLP位点进行了调查，发现存在10种不同的单倍型。根据该样本估计的曼登卡人中导致突变的镰状细胞性贫血(β(S))的频率为11.7%。该突变被发现与单一的塞内加尔单倍型严格相关。对94条染色体的一个子集的大约600个碱基的β-珠蛋白基因上游区域进行了测序，显示存在4个颠换、5个转换和一个复合微卫星多态。22条S(Beta)染色体的序列也与先前定义的塞内加尔单倍型完全相同，表明这种突变是非常新的。使用蒙特卡罗模拟(允许特定的平衡选择模型、人口的逻辑增长和塞内加尔单倍型的可变初始频率)来估计β(S)突变的年龄。由此产生的最大似然估计为45-70代(1350-2100年)，适用于非常不同的人口情景。最小的置信度区间(25-690代)是在假设曼登卡种群是大的(N-c>；5,000)和稳定的，或者它已经经历了快速的人口扩张到目前的>；5,000个繁殖个体的大小的假设下获得的，考虑到在beta(A)染色体上发现的巨大的多样性，这是很有可能的。
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-c >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.