Slimowitz J R, Cohen J E
Department of Mathematics, Duke University, Durham, NC.
Am J Hum Genet. 1993 Aug;53(2):314-23.
The National Research Council recommended the use of the ceiling principle in forensic applications of DNA testing on the grounds that the ceiling principle was believed to be "conservative," giving estimates greater than or equal to the actual genotype frequencies in the appropriate reference population. We show here that the ceiling principle can fail to be conservative in a population with two subpopulations and two loci, each with two alleles at Hardy-Weinberg equilibrium, if there is some linkage disequilibrium between loci. We also show that the ceiling principle can fail in a population with two subpopulations and a single locus with two alleles if Hardy-Weinberg equilibrium does not hold. We give explicit analytical formulas to describe when the ceiling principle fails. By showing that the ceiling principle is not always mathematically reliable, this analysis gives users of the ceiling principle the responsibility of demonstrating that it is conservative for the particular data with which it is used. Our reanalysis of VNTR data bases of the FBI provides compelling evidence of two-locus associations within three major ethnic groups (Caucasian, black, and Hispanic) in the United States, even though the loci tested are located on different chromosomes. Before the ceiling principle is implemented, more research should be done to determine whether it may be violated in practice.
美国国家研究委员会建议在DNA检测的法医应用中采用上限原则，理由是上限原则被认为是“保守的”，能给出大于或等于适当参考人群中实际基因型频率的估计值。我们在此表明，如果基因座之间存在一些连锁不平衡，那么在一个有两个亚群和两个基因座（每个基因座在哈迪 - 温伯格平衡状态下有两个等位基因）的群体中，上限原则可能并不保守。我们还表明，如果哈迪 - 温伯格平衡不成立，那么在一个有两个亚群和一个有两个等位基因的单基因座的群体中，上限原则也可能失效。我们给出了明确的分析公式来描述上限原则何时失效。通过表明上限原则在数学上并非总是可靠的，该分析让使用上限原则的人有责任证明它对于所使用的特定数据是保守的。我们对联邦调查局的VNTR数据库的重新分析提供了令人信服的证据，表明在美国的三个主要种族群体（白种人、黑人和西班牙裔）中存在双基因座关联，尽管所检测的基因座位于不同的染色体上。在实施上限原则之前，应该进行更多的研究以确定它在实际应用中是否可能被违反。
