Gene mapping and marker clustering using Shannon´s mutual information

Finding the causal genetic regions underlying complex traits is one of the main aims in human genetics. In the context of complex diseases, which are believed to be controlled by multiple contributing loci of largely unknown effect and position, it is especially important to develop general yet sensitive methods for gene mapping. We discuss the use of Shannon´s information theory for population-based gene mapping of discrete and quantitative traits and for marker clustering. Various measures of mutual information were employed in order to develop a comprehensive framework for gene mapping analyses. An algorithm aimed at finding so-called relevance chains of causal markers is proposed. Moreover, entropy measures are used in conjunction with multidimensional scaling to visualize clusters of genetic markers. The relevance chain algorithm successfully detected the two causal regions in a simulated scenario. The approach has also been applied to a published clinical study on autoimmune (Graves´) disease. Results were consistent with those of standard statistical methods, but identified an additional locus of interest in the promoter region of the associated gene CTLA4. The developed software is freely available at http://www.lnt.ei.tum.de/download/InfoGeneMap/