Development and implementation of linkage-analysis methods for the genetic mapping of complex traits

该项目的目标是评估、进一步发展和实施复杂性状遗传图谱的连锁分析方法。该项目的第一部分是与MOD得分分析，其中参数LOD得分最大化的性状模型参数。我们的小组以前实施了MOD评分分析常染色体遗传位点的二分性状。通过进行模拟以及通过分析反射，将评估疾病模型参数在多大程度上可以通过MOD评分分析来估计不同大小的谱系。MOD分数检测复杂性状（包括具有印记或代谢干扰的性状）的连锁的能力将与其他方法的能力进行比较。研究人员还计划调查男性和女性基因图谱之间的差异在多大程度上会导致错误的结论，即印迹存在。此外，将对X染色体基因座实施二分性状的MOD评分分析。另一个目标是设计和实施定量表型的MOD评分分析。该项目的第二部分涉及全基因组参数连锁分析的实施，明确模拟两个性状基因座。这种系统的二维方法将允许全基因组评估两个基因座的相互作用，也为那些性状的遗传作图，没有显着的效果时，可以观察到只有一个基因座。

The goal of this project is to assess, further develop, and implement methods of linkage analysis for the genetic mapping of complex traits. The first part of the project is concerned with MOD-score analysis, in which the parametric LOD score is maximized over the trait-model parameters. Our group has previously implemented a MOD-score analysis of dichotomous traits for autosomal genetic loci. By performing simulations as well as by analytical reflections, it will be assessed to what degree the disease-model parameters can be estimated by a MOD-score analysis for pedigrees of different sizes. The power of MOD scores to detect linkage for complex traits, including those with imprinting or metabolic interference, will be compared to the power of other methods. It is also planned to investigate to what degree a difference between the male and female genetic map can spuriously lead to the conclusion that imprinting is present. In addition, MOD-score analysis of dichotomous traits will be implemented for X-chromosomal loci. A further goal is to devise and implement a MOD-score analysis for quantitative phenotypes. The second part of the project addresses the implementation of a genome-wide parametric linkage analysis which explicitly models two trait loci. Such a systematic two-dimensional approach will allow for the genome-wide evaluation of two-locus interactions, and also for the genetic mapping of those traits for which no marked effect can be observed when looking at only one locus.