Behöver vi förändra sättet vi beskriver kopplingen mellan genotyp och fenotyp i studier av komplexa egenskaper?
Tidsperiod: 2018-01-01 till 2021-12-31
Projektledare: Örjan Carlborg
Budget: 3 375 000 SEK
Genotype-to-phenotype mapping is a core feature of genetics. These maps describe how combinations of DNA variants (genotypes) contribute to the appearance (the phenotype) of an individual organism. Staggering amounts of genetic data is generated today with the aim to improve e.g. our understanding of life and disease, and facilitate development of new diagnostics, cures and ways to manage our natural resources. Today, however, not even the most powerful studies in humans (including >100,000 individuals) can explain more than a fraction of the heritability of these traits. We therefore need to explore the data beyond the current norm that assumes that genes combine their effects additively. In this project, I will empirically challenge additive and more complex models with data from a yeast population where experimentally revealed epistasis (genetic interactions) and gene-by-environment interactions determine the phenotypes. This work will reveal the limits of the current quantitative genetic modeling framework and provide novel empirical insights to its strengths and weaknesses. The results will allow us to provide guidelines for how to make most efficient use of the current models to detect, and interpret results from, studies of complex traits and diseases in animals, plants and humans. They will also reveal key areas where future work is needed to develop approaches that allow exploration and modeling genetic architectures beyond what can be done today.