Hodge S E, Vieland V J
Department of Psychiatry, New York State Psychiatric Institute, New York 10032, USA.
Genetics. 1996 Nov;144(3):1215-23. doi: 10.1093/genetics/144.3.1215.
We propose a fundamental new definition of single ascertainment, namely, that single ascertainment is any ascertainment scheme in which P[pedigree is ascertained/true structure of pedigree] alpha p(theta), where p(theta) is some function of genetic parameters theta but is not a function of pedigree structure. Stated in words: Under single ascertainment, all pedigrees have equal (or proportional with respect to genetic parameters) probabilities of being ascertained, independent of pedigree size or structure. This new definition of single ascertainment allows us to show several results: (1) The correct likelihood consists of the probability of the data conditioned on the observed pedigree, divided by the function p(theta), whether sampling is "proband-independent" or "proband-dependent." (2) More-familiar definitions of single ascertainment all represent special cases of our definition. (3) When p(theta) represents the prevalence of the trait being studied, our definition corresponds to "classical" single ascertainment, i.e., ascertainment through a single "proband." However, the concept of p(theta) can also be generalized to represent the population frequency of configurations of affected relatives (such as affected sib pairs); we call this "generalized single ascertainment."
我们提出了一种关于单系谱确定的全新基本定义，即单系谱确定是指任何一种系谱确定方案，其中P[系谱被确定/系谱的真实结构]α p(θ)，这里p(θ)是遗传参数θ的某个函数，但不是系谱结构的函数。用文字表述就是：在单系谱确定情况下，所有系谱被确定的概率相等（或相对于遗传参数成比例），与系谱大小或结构无关。这种单系谱确定的新定义使我们能够证明几个结果：（1）正确的似然性由以观察到的系谱为条件的数据概率除以函数p(θ)组成，无论抽样是“先证者独立”还是“先证者相关”。（2）更常见的单系谱确定定义均为我们定义的特殊情况。（3）当p(θ)表示所研究性状的患病率时，我们的定义对应于“经典”单系谱确定，即通过单个“先证者”进行确定。然而，p(θ)的概念也可以推广到表示受影响亲属构型（如受影响的同胞对）的群体频率；我们将此称为“广义单系谱确定”。
