Systems genetics: challenges and developing strategies

Systems genetics is a new discipline based on the transcription mapping, which is also called “genetical genomics”. In recent years, systems genetics has become more practical because of advances in science and technology. Analysis of expression quantitative trait loci (eQTLs) is an emerging technique in which individuals are genotyped across a panel of genetic markers and, simultaneously, phenotyped using DNA microarrays. Depending on eQTL mapping, one can infer the underlying regulatory network responsible for complex diseases or quantitative trait phenotypes. Systems genetics approaches integrate DNA sequence variation, variation in transcript abundance and other molecular phenotypes and variation in organismal phenotypes in a linkage or association mapping population, and allow us to interpret quantitative genetic variation in terms of biologically meaningful causal networks of correlated transcripts. These approaches have been made possible due to the development of massively parallel technologies for quantifying genome-wide levels of transcript abundance. The predictive power of the networks could be enhanced by more systematically integrating protein-protein interactions, protein-DNA interactions, protein-RNA interactions, RNA-RNA interactions, protein state information, methylation state, and interactions with metabolites. Systems genetics research will change the traditional approaches based on reductionism, and allows us to reconsider the living phenomenon and complex disease mechanism. Systems genetics benefits from varied “omics” researches (such as transcriptomics, metabolomics, and phenomics) and the development of bioinformatics tools and mathematical modeling, and will become mature in the near future like many other branches of genetics. Systems genetics is leading researchers to understand genetics systems from holism’s viewpoint, and will open a wide field of vision for genetics researchers in systems biology era.