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This article is part of the supplement: UT-ORNL-KBRIN Bioinformatics Summit 2010

Open Access Poster presentation

Linking genotype to phenotype with Bayesian network modeling of Chlamydia infection

Jesse D Ziebarth1*, Bao Li1, Isao Miyairi12 and Yan Cui13

Author Affiliations

1 Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA

2 Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA

3 Center of Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, TN 38163, USA

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BMC Bioinformatics 2010, 11(Suppl 4):P19  doi:10.1186/1471-2105-11-S4-P19

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2105/11/S4/P19


Published:23 July 2010

© 2010 Ziebarth et al; licensee BioMed Central Ltd.

Background

Understanding the causal pathways that link genotypes with gene expression and higher order phenotypes, such as disease susceptibility, has been a recent goal of systems genetic studies. Pairwise correlations can select genes and phenotypes that are associated with a common genetic locus; however, the directions of these links are more difficult to determine. We propose a method in which Bayesian networks are used to establish causal pathways from genotype to gene expression to phenotype and apply it to mice infected with Chlamydia psittaci.

Results

Recombinant inbred BXD mice strains have been previously used to study the genetic differences that cause a much greater resistance to Chlamydia psittaci infection in C57BL/6J mice compared with DBA/2J mice [1]. Gene expression levels and higher order phenotypes, such as pathogen load and survival, were collected for 44 BXD strains. Directed graphs linking SNPs [2] in the BXD genomes to this data were created with QTL mapping and the Bayesian network method. Figure 1 shows a selection of the resulting causal pathways; many of the genes in these pathways are known to be associated with immune response or GTPase activity, which has been linked to Chlamydia psittaci infection [1].

thumbnailFigure 1. Causal pathways linking genotype SNPs to gene expression levels to phenotypes in BXD mice infected with Chlamydia psittaci

Acknowledgements

This work was support by NIH grant AI081050 and DOD grant W81XHW-05-01-0227.

References

  1. Miyairi I, Tatireddigari VRRA, Mahdi OS, Rose LA, Belland RJ, Lu L, Williams RW, Byrne GI: The p47 GTPases Iigp2 and Irgb10 regulate innate immunity and inflammation to murine Chlamydia psittaci infection.

    J Immunol 2007, 179:1814-1824. PubMed Abstract | Publisher Full Text OpenURL

  2. BXD Genotypes at the GeneNetwork [http://www.genenetwork.org/genotypes/BXD.geno] webcite