Search

In human genetic analysis, data are collected through the so-called 'ascertainment procedure'. Statistically this sampling scheme can be thought of as a multistage sampling method. At the first stage, one or several probands are ascertained. At the subsequent stages, a sequential sampling scheme is applied. Sampling in such a way is virtually a nonrandom procedure, which, in most cases, causes biased estimation which may be intractable. This paper focuses on the underlying causes of the intractability problem of ascertained genetic data. Three types of parameters, i.e. target, design and nuisance parameters, are defined as the essences to formulate the true likelihood of a set of data. These parameters are also classified into explicit or implicit parameters depending on whether they can be expressed explicity in the likelihood function. For ascertained genetic data, a sequential scheme is regarded as an implicit design parameter, and a true pedigree structure as an implicit nuisance parameter. The intractability problem is attributed to loss of information of any implicit parameter in likelihood formulation. Several approaches to build a likelihood for estimation of the segregation ratio when only an observed pedigree structure is available are proposed., (Copyright 2001 S. Karger AG, Basel)

Testing the nonrandomness of breakage at a chromosome band is an essential step fo identifying a fragile site. In this paper, we propose a method derived by using the relationship between the binomial and F distributions for testing nonrandomness. The method is simple in calculation. It was applied to the detection of fragile sites for Chinese patients with colorectal carcinoma.

In linkage analysis a single-child family is usually considered to be completely uninformative. This article shows that such a family can provide information on linkage disequilibrium, even if it provides no information on linkage equilibrium. A transition matrix consisting of the recombination fraction and the phase proportion is proposed to study the genetic transmission from a pair of parents to their single child. The information about linkage for a single-child family is shown to be confounded by the phase proportion. This explains why such a family used to be considered uninformative under the assumption of linkage equilibrium. By reparametrizing the recombination fraction and the phase proportion into one parameter, it is demonstrated that extracting information on linkage disequilibrium is feasible. The study of power of the testing method proposed here is carried out by simulation.