Keays David A, Clark Taane G, Flint Jonathan
Psychiatric Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
Mamm Genome. 2006 Mar;17(3):230-8. doi: 10.1007/s00335-005-0101-4. Epub 2006 Mar 3.
N-ethyl-N-nitrosourea (ENU) is a widely used mutagen in genotypic and phenotypic screens aimed at elucidating gene function. The high rate at which ENU induces point mutations raises the possibility that an observed phenotype may be to the result of another unidentified linked mutation. This article presents methods for estimating the probability of additional linked coding mutations (1) in a given region of DNA using both Poisson and Bayesian models and in (2) an F(1) animal exposed to ENU that has undergone b number of backcrosses. Applying these methods to the mouse data set of Quwailid et al., we estimate that the probability that a confounding mutation is linked to a cloned mutation when the candidate region is 5 Mb is very slim (p < 0.002). Where mutants are identified by genotypic methods, we show that backcrossing in the absence of marker-assisted selection is an inefficient means of eliminating linked confounding mutations.
N-乙基-N-亚硝基脲（ENU）是一种广泛应用于基因型和表型筛选以阐明基因功能的诱变剂。ENU诱导点突变的高频率增加了一种可能性，即观察到的表型可能是另一个未鉴定的连锁突变的结果。本文介绍了使用泊松模型和贝叶斯模型估计（1）给定DNA区域以及（2）在经过b次回交的暴露于ENU的F(1)动物中额外连锁编码突变概率的方法。将这些方法应用于Quwailid等人的小鼠数据集，我们估计当候选区域为5 Mb时，一个混杂突变与一个克隆突变连锁的概率非常小（p < 0.002）。当通过基因型方法鉴定突变体时，我们表明在没有标记辅助选择的情况下进行回交是消除连锁混杂突变的低效方法。
