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培养的哺乳动物细胞群体中突变率估计方法的评估。

Evaluation of methods for the estimation of mutation rates in cultured mammalian cell populations.

作者信息

Li I C, Chu E H

出版信息

Mutat Res. 1987 Apr;190(4):281-7. doi: 10.1016/0165-7992(87)90010-8.

DOI:10.1016/0165-7992(87)90010-8
PMID:3550454
Abstract

A systematic comparison of 5 different statistical methods for the estimation of mutation rate (mu) in cultured Chinese hamster V79 cells is presented. Fluctuation tests were performed with several large batches of parallel cell cultures each allowed to grow for a different length of time in order to reach different population size (Nt). Based on Lea and Coulson's theoretical distribution, a comparison has been made between the experimental data and the expected distribution of the number of ouabain-resistant mutants per culture in these hamster cell populations. The sum of squared deviation between the observed and expected values, or SSD, was used as a means of the adequacy of the estimation method; the method which gives the smallest SSD is regarded as the best one for the estimation of mu. Our results show that when Nt is small, the occurrence of mutation is infrequent, and SSDs from different methods are similar. However, when Nt is large, there is a great discrepancy of the SSD values, suggesting a preference of using the maximum likelihood method, the Po method, the median method, the upper quartile method and the mean method, in that order, for the estimation of mu. The order of preference is correlated with estimation efficiencies. Depending on the size of Nt and the method used, the estimated mu may vary up to more than 3-fold. At a large Nt, the mu obtained from the maximum likelihood method is very precise. This suggests the importance of choosing an appropriate Nt as well as method for the estimation of mu.

摘要

本文对用于估计中国仓鼠V79细胞系中突变率(μ)的5种不同统计方法进行了系统比较。进行了波动试验,使用了几大批平行细胞培养物,每种培养物允许生长不同的时间长度,以达到不同的群体大小(Nt)。基于Lea和Coulson的理论分布,对这些仓鼠细胞群体中每种培养物中哇巴因抗性突变体数量的实验数据和预期分布进行了比较。观测值与预期值之间的平方偏差之和,即SSD,被用作估计方法是否合适的一种衡量标准;给出最小SSD的方法被认为是估计μ的最佳方法。我们的结果表明,当Nt较小时,突变发生频率较低,不同方法的SSD相似。然而,当Nt较大时,SSD值存在很大差异,这表明在估计μ时,按顺序优先使用最大似然法、Po法、中位数法、上四分位数法和均值法。优先顺序与估计效率相关。根据Nt的大小和所使用的方法,估计的μ可能相差超过3倍。在Nt较大时,通过最大似然法获得的μ非常精确。这表明选择合适的Nt以及方法对于估计μ的重要性。

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1
Evaluation of methods for the estimation of mutation rates in cultured mammalian cell populations.培养的哺乳动物细胞群体中突变率估计方法的评估。
Mutat Res. 1987 Apr;190(4):281-7. doi: 10.1016/0165-7992(87)90010-8.
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引用本文的文献

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Mutation frequency dynamics in HPRT locus in culture-adapted human embryonic stem cells and induced pluripotent stem cells correspond to their differentiated counterparts.适应培养的人胚胎干细胞和诱导多能干细胞中HPRT基因座的突变频率动态与其分化后的对应细胞一致。
Stem Cells Dev. 2014 Oct 15;23(20):2443-54. doi: 10.1089/scd.2013.0611. Epub 2014 Jul 25.
2
Embryonic stem cells and somatic cells differ in mutation frequency and type.胚胎干细胞和体细胞在突变频率和类型上有所不同。
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3586-90. doi: 10.1073/pnas.062527199. Epub 2002 Mar 12.
3
Rates of spontaneous mutation in an archaeon from geothermal environments.
来自地热环境的古生菌的自发突变率。
J Bacteriol. 1997 May;179(10):3298-303. doi: 10.1128/jb.179.10.3298-3303.1997.
4
Bayesian procedures for the estimation of mutation rates from fluctuation experiments.用于从波动实验估计突变率的贝叶斯方法。
Genetics. 1996 Jan;142(1):313-26. doi: 10.1093/genetics/142.1.313.
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Luria-Delbrück fluctuation experiments: design and analysis.卢里亚-德尔布吕克波动实验:设计与分析
Genetics. 1994 Mar;136(3):1209-16. doi: 10.1093/genetics/136.3.1209.