Linkage disequilibrium mapping and other applications

融合过程是一种用于模拟种群谱系的随机过程，近年来引起了人们的广泛关注，这主要是因为它在人类遗传学研究中的大量应用。我们已经开发了一种方法，它使用具有复合的结合过程(Larribe等人)。2002，Larribe 2004)，以估计影响疾病的基因突变的位置，例如，进行基因精细定位。在最近使用复合似然策略提高了估计的稳定性(Larribe和Morgan，2004)之后，我们建议在复杂遗传病的背景下开发该方法，这是当今人类遗传学的主要兴趣。我们的目标是建立不完全外显率和表现率参数的模型，并将它们视为估计中的滋扰参数，就像我们处理未知家系的方式一样。此外，我们希望开发这种方法，使其能够同时估计两个突变的位置。最后，我们希望通过对从今天起到观察到的序列具有共同祖先的一段时间内疾病突变的频率进行建模，来纠正确定偏差(病例和对照的不同抽样)。

The coalescent process, a stochastic process used to simulate population genealogies, has attracted much attention recently, mostly due to the numerous applications in human genetics research. We have developed a method, which uses the coalescent process with recombination (Larribe et al. 2002, Larribe 2004) to estimate the location of a genetic mutation influencing a disease, e.g. to do genetic fine mapping. After having recently improved the stability of the estimates using a composite likelihood strategy (Larribe and Morgan, 2004), we propose to develop the method in the context of complex genetic disease, which is of major interest in human genetics today. The goal is to model parameters of incomplete penetrance and phenocopy rate, and treat them as nuisance parameters in the estimation, in a similar way as we do with unknown genealogies. Morover, we would like to develop the method so that it is capable of estimating the position of two mutations simultaneously. Finally, we want to correct for the ascertainment biases (unequal sampling of cases and controls), by modelling the frequency of the disease mutation over time, from today back until the observed sequences have a common ancestor.