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

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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.