Kinghorn B P, Kennedy B W, Smith C
Department of Animal Science, University of New England, Australia.
Genetics. 1993 May;134(1):351-60. doi: 10.1093/genetics/134.1.351.
This paper describes a method for screening animal populations on an index of calculated probabilities of genotype status at an unknown single locus. Animals selected by such a method might then be candidates in test matings and genetic marker analyses for major gene detection. The method relies on phenotypic measures for a continuous trait plus identification of sire and dam. Some missing phenotypes and missing pedigree information are permitted. The method is an iterative two-step procedure, the first step estimates genotype probabilities and the second step estimates genotypic effects by regressing phenotypes on genotype probabilities, modeled as true genotype status plus error. Prior knowledge or choice of major locus-free heritability for the trait of interest is required, plus initial starting estimates of the effect on phenotype of carrying one and two copies of the unknown gene. Gene frequency can be estimated by this method, but it is demonstrated that the consequences of using an incorrect fixed prior for gene frequency are not particularly adverse where true frequency of the allele with major effect is low. Simulations involving deterministic sampling from the normal distribution lead to convergence for estimates of genotype effects at the true values, for a reasonable range of starting values, illustrating that estimation of major gene effects has a rational basis. In the absence of polygenic effects, stochastic simulations of 600 animals in five generations resulted in estimates of genotypic effects close to the true values. However, stochastic simulations involving generation and fitting of both major genotype and animal polygenic effects showed upward bias in estimates of major genotype effects. This can be partially overcome by not using information from relatives when calculating genotype probabilities-a result which suggests a route to a modified method which is unbiased and yet does use this information.
本文描述了一种基于未知单基因座基因型状态计算概率指数对动物群体进行筛选的方法。通过这种方法选择的动物随后可能成为用于检测主基因的测交和遗传标记分析的候选对象。该方法依赖于对一个连续性状的表型测量以及父母的识别。允许存在一些缺失的表型和系谱信息。该方法是一个迭代的两步程序，第一步估计基因型概率，第二步通过将表型对基因型概率进行回归来估计基因型效应，将基因型概率建模为真实基因型状态加上误差。需要对感兴趣的性状有先验知识或选择无主基因座的遗传力，以及对携带未知基因一份和两份时对表型的影响的初始起始估计值。基因频率可以通过这种方法估计，但结果表明，当具有主要效应的等位基因的真实频率较低时，使用不正确的固定先验基因频率的后果并非特别不利。涉及从正态分布进行确定性抽样的模拟表明，对于合理范围的起始值，基因型效应估计值会收敛到真实值，这说明主基因效应的估计有合理的依据。在不存在多基因效应的情况下，对五代中600只动物进行的随机模拟得出的基因型效应估计值接近真实值。然而，涉及主基因型和动物多基因效应的产生和拟合的随机模拟表明，主基因型效应估计值存在向上偏差。在计算基因型概率时不使用亲属的信息可以部分克服这一问题——这一结果提示了一种改进方法的途径，该方法无偏差且仍使用此信息。
