COMPUTER-SIMULATION METHODS IN HUMAN LINKAGE ANALYSIS
COMPUTER-SIMULATION METHODS IN HUMAN LINKAGE ANALYSIS
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DOI：
10.1073/pnas.86.11.4175
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发表时间：
1989-06-01
影响因子：
11.1
通讯作者：
OTT, J
中科院分区：
文献类型：
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作者：
OTT, J
在人类连锁分析中，许多没有解析解的统计问题可以用特别的蒙特卡罗方法来解决，蒙特卡罗方法是一种适用于家系成员的有效的计算机模拟方法。本文描述了一种在一个或多个标记座位上随机产生遗传型的一般方法，给出了它们之间以及与标记相连的座位上观察到的表型。该方法基于众所周知的将给定表型的基因型的多变量概率展开为条件单变量概率的乘积的公知扩展，条件单变量概率可被视为对应于条件独立的单变量随机变量。这种表示法允许递归地评估单变量概率，在给定观察到的表型和已经生成的标记基因型的情况下，可以通过执行关于标记基因型的连续的“风险计算”，以一种令人惊讶的简单的方式来实现该单变量概率。讨论了各种悬而未决的问题的潜在应用。该方法被应用于28个已发表的遗传性运动和感觉神经病I和Duffy(Fy)血型基因座之间的遗传连锁分析，证实了遗传性运动和感觉神经病I的异质性。在连锁程序包中开发的模拟方法将于1989年晚些时候实现。
In human linkage analysis, many statistical problems without analytical solution could be solved by ad hoc Monte Carlo procedures were efficient computer-simulation methods available for members of family pedigrees. In this paper, a general method is described for randomly generating genotypes at one or more marker loci, given observed phenotypes at loci linked among themselves and with the markers. The method is based on a well-known expansion of the multivariate probability of genotypes, given phenotypes, into a product of conditional univariate probabilities that may be viewed as corresponding to conditionally independent univariate random variables. This representation allows a recursive evaluation of the univariate probabilities that can be implemented in a surprisingly simple manner by carrying out successive "risk calculations" with respect to marker genotypes, given observed phenotype and marker genotypes already generated. Potential applications to various unresolved problems are discussed. The method is applied to 28 published families analyzed for genetic linkage between hereditary motor and sensory neuropathy I and the Duffy (FY) blood group locus and confirms heterogeneity of hereditary motor and sensory neuropathy I. An implementation of the simulation methods developed in the LINKAGE program package will be available later in 1989.