Jeanpierre M
Service de Biochimie Génétique et Unité INSERM U129, CHU Cochin, Paris, France.
J Med Genet. 1988 Oct;25(10):663-8. doi: 10.1136/jmg.25.10.663.
Calculation of carrier risk of an X linked disease may be performed on a small computer after DNA analysis, but a method for rapid hand estimation of the risk is still useful for a quick check of the results and weighing the relative importance of each element of information, such as the determination of a haplotype. Each risk estimation is a function of a prior risk and the product of likelihood ratios and these terms are derived themselves from parameters such as fitness or the relative mutation rate in male and female gametes. Even if it is often difficult to have strong experimental estimation of these variables, the existence of a normal father or grandfather must be considered whenever male fitness is not null. The likelihood ratio for a woman for not being a carrier, when her father is not affected and her mother has herself a likelihood R for not having the mutated gene, may be expressed as the ratio 2R/(CmR + 1), with Cm being a function of male fitness and relative mutation rate. Cm represents the odds ratio for the mother of a carrier not to be a carrier, given that the father of the known carrier is not affected. This formula can be used recurrently and reduces to 2R/(R + 1) in lethal X linked disease. When likelihood ratios are expressed as an algebraic function, maximum values are easily determined, hence fixing the limits of DNA analysis.
在进行DNA分析后，可在小型计算机上计算X连锁疾病的携带者风险，但一种快速手工估算风险的方法对于快速检查结果以及权衡每条信息要素（如单倍型的确定）的相对重要性仍然很有用。每次风险评估都是先验风险与似然比乘积的函数，而这些项本身又源自诸如适合度或雄雌配子相对突变率等参数。即便通常很难对这些变量进行有力的实验估计，但只要男性适合度不为零，就必须考虑正常父亲或祖父的存在。当一名女性的父亲未受影响且其母亲自身携带突变基因的可能性为R时，该女性不是携带者的似然比可表示为2R/(CmR + 1)，其中Cm是男性适合度和相对突变率的函数。Cm表示已知携带者的父亲未受影响时，携带者母亲不是携带者的优势比。此公式可反复使用，在致死性X连锁疾病中简化为2R/(R + 1)。当似然比表示为代数函数时，很容易确定最大值，从而确定DNA分析的限度。
