Description du projet
Sources de variation phénotypique chez les vertébrés complexes
Le projet IndiGene, financé par l’UE, entend étudier en profondeur et caractériser les sources de variation entraînant la variabilité des phénotypes chez les vertébrés complexes. Le projet caractérisera les sources de variations génétiques et environnementales et la variation stochastique individuelle survenant même dans des conditions génétiques et environnementales fixes. Les chercheurs ont sélectionné le poisson médaka (poisson japonais originaire des rizières) comme modèle et ont procédé au séquençage du génome entier d’un panel de 111 médakas individuels différents de même provenance. Ils prévoient maintenant d’étudier les phénotypes de ces poissons en utilisant une structure à forte réplication, allant de l’organisme aux phénotypes moléculaires. Les données seront analysées à l’aide de méthodes de pointe pour répartir les variations entre les composantes génétiques, environnementales et stochastiques et leurs interactions.
Objectif
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.
Champ scientifique
Not validated
Not validated
Programme(s)
Thème(s)
Régime de financement
ERC-SyG - Synergy grantInstitution d’accueil
69117 Heidelberg
Allemagne