In the past decade, genome-wide association studies have led to the discovery of common genetic alleles conferring only modest effects on disease risks. Rare and low-frequency genetic variants have been less studied although they are likely to play a substantial role in disease susceptibility.
The FROGH project aims to provide novel tools to explore links between demography, genetics, history and variants distribution in France. The FROGH Team aims to create the conditions to highlight the genetic architecture of complex disease and explore the role of rare and low-frequency variants in diseases.
The assumptions behind this project are that rare and low-frequency genetic variants, playing a substantial role in disease susceptibility, have arisen more recently and are still concentrated in limited geographical areas. This assumptions are supported,by preliminary results conducted by us on two datasets of French individuals.
This question will be addressed by exploring genetic data of rural populations in northern and western France. Firstly, the individual genomes of 664 whole genome sequenced new French individuals, funded elsewhere, with local ancestry will be studied. A database of the genetic variants discovered will be set up and proposed as a French reference panel to further genetic studies together with a haplotype reference panel. Tools linked to this database will be developed to guide the design of association studies with complex traits.
Secondly, the study of the reference panel will allow to ascertain the genetic structure of French population and to infer the processes that have shaped genomic variation in France.
Lastly, we will assess the contribution of sequencing ancient DNA in order to improve our understanding of demographic processes that gave rise to the current genetic structure and provide information about genetic make-up of both ancient and present French population.
The data generated in FROGH will be an invaluable resource to better understand the genetic structure of European populations in relation with their historical habits. Furthermore, the FROGH project will contribute to the construction of a French Genome Reference Panel and help France in taking a better place in International consortia dedicated to human genetics.
The FROGH consortium gathers partners involved for long in population genetics, genetic epidemiology, bioinformatics and ancient DNA analysis. All partners have collaborated in common research projects and papers on the subject of statistical genetics and population genetics have already been published involving at least two members.
Monsieur Christian Dina (l'institut du thorax)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
CNRS UMR 5525 Laboratoire TIMC-IMAG
Evolutionary Biology Centre (EBC) - Upps Department of Evolutionary Biology
IJM Institut Jacques Monod
CEA - CNG Commissariat à l'energie atomique et aux energies alternatives
UMR1078 GENETICS, FUNCTIONAL GENOMICS AND BIOTECHNOLOGY
INSERM UMR 1087 / CNRS UMR 6291 l'institut du thorax
Help of the ANR 437,765 euros
Beginning and duration of the scientific project: - 36 Months