Individuality is both the defining feature of us and an important factor that affects our well-being. Genetic, environmental and random variation must all be understood if we hope to realize personalized medicine and fully understand biological systems across species. Our central aim is to investigate the sources of variation that result in differences between individuals, focussed primarily on understanding the contribution and interactions between genetic, environmental and stochastic variation with respect to trait association mapping in Medaka fish.
This project makes use of the unique properties of medaka fish. Medaka can be fully inbred from the wild, are fertile and we have already sequenced a panel of 111 inbred medaka lines originating from a single natural population.
We will carry out in-depth profiling of these fish at multiple scales, ranging from molecular measurements to full organisms. We will analyse a number of traits in wild fish from the same source population, which will both increase our research potential and place our discoveries in the same context as human observational studies. A particular focus will be integrating this information across the cardiovascular systems, especially in comparison to human disease. A central strategy that we will use across most of our trait association mapping experiments is the full phenotyping across all MIKK panel lines followed by the design and selection of specific lines showing differential phenotype distributions for these traits to cross into F1 and F2 generations. Following the successful generation of large F2 populations all F2 offspring are then sequenced and phenotyped allowing genetic association mapping to be performed using techniques such as linear mixed models. Critically, this approach allows us to have a high level of control on all mentioned sources of variation and to explicitly test their interaction terms during association testing.
We will provide and distribute the inbred medaka lines to other research groups who can apply their own projects across the panel. This study will focus on the question of distinguishing between variation that occurs due to genetic, individual and environmental effects. This will lead to a more complete understanding of variation related to human disease and well-being.
