Project description
Sources of phenotypic variation in complex vertebrates
The goal of the EU-funded IndiGene project is the in-depth study and characterisation of the sources of variation resulting in phenotype variability in complex vertebrates. The project will characterise the genetic and environmental sources of variation and individual stochastic variation occurring even in fixed genetic and environmental conditions. Researchers selected the medaka fish (Japanese rice fish) as a model, and inbred and performed whole-genome sequencing of a panel of 111 diverse individual medaka from a single location. Now they plan to study the phenotypes of these fish using a high-replication structure, ranging from organism to molecular phenotypes. The data will be analysed using state-of-the-art methods to partition variation between genetic, environmental and stochastic components and their interactions.
Objective
We propose to thoroughly investigate and characterise the sources of variation that results in varying phenotypes in a complex vertebrate. As well as characterising the genetic and environmental sources of variation, we will also investigate individual stochastic variation present even in fixed settings (both genetically and environmentally). To achieve this we will exploit the unique properties of Medaka fish, which can be fully inbred from the wild. We have already inbred and performed whole genome sequencing of a panel of 111 diverse Medaka fish from a single location; we propose to phenotype these fish in depth with high replication structure, ranging from organismal to molecular phenotypes. We will also phenotype entirely wild fish from the same source population as the panel with a subset of the phenotypes. We will analyse the data using state of the art methods to partition variation between genetic, environmental and stochastic components, and their interactions. We will integrate across both the different levels of phenotypic information across the cardiovascular system, and also across vertebrate phenotypes, in particular the extensive human phenotypes. By using genetic crosses and CRISPR-Cas9 techniques we will definitively prove specific interactions. We will host a “Research Hotel” for other phenotyping schemes to be applied to this panel, in particular from the Zebrafish community. This comprehensive and carefully replicated study will allow us to understand the opportunities and limitations of genetic stratification and personalised medicine in humans.
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Funding Scheme
ERC-SyG - Synergy grantHost institution
69117 Heidelberg
Germany