Title :

The French Exome (FREX) Project: A Population-based Panel of Exomes to Help Filter Out Common Local Variants

Author(s) :

Genin, Emmanuelle [Auteur]
Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) [GGB]
Redon, Richard [Auteur]
ITX - unité de recherche de l'institut du thorax [ITX]
Deleuze, Jean-François [Auteur]
Centre National de Génotypage [CNG]
Campion, Dominique [Auteur]
Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques [GPMCND]
Lambert, Jean-Charles [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Dartigues, Jean-François [Auteur]
Laboratoire de Biotechnologie et Microbiologie Appliquée [LBMA]
Consortium, Frex [Auteur]

Journal title :

Genetic Epidemiology

Pages :

691-691

Publisher :

Wiley

Publication date :

2017

ISSN :

0741-0395

HAL domain(s) :

Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]
Sciences du Vivant [q-bio]/Génétique

English abstract : [en]

High-throughput sequencing technologies enable the characterization of all the genetic variations in the exomes of individuals and the discovery of novel variants involved in monogenic and complex diseases. The study of ...
Show more >High-throughput sequencing technologies enable the characterization of all the genetic variations in the exomes of individuals and the discovery of novel variants involved in monogenic and complex diseases. The study of these two kinds of diseases requires different methods and raises specific problems with a major challenge of understanding the functional role of the identified variants to filter out the neutral ones. For this purpose, investigators often rely on the observed frequencies of variants in public databases. However, these public databases are not well representatives of the different ancestries in Europe and this is true in particular for France. Indeed, comparing the exomes of 573 individuals sampled in 6 different regions of France to the frequency data available in GnomAD, we identified several variants with significant allele frequency differences. We also found that, compared to the different public panels, the “French exomes” allow a more efficient filtering of variants leading to a substantial reduction in the number of candidate variants retained for validation. Allele frequency differences are also detected within France between the different geographic regions, pointing out, for example, to some variants that could have been under positive selection. At this fine geographical scale, we were able to detect differences in the rare variant burden of several genes that could have consequences for the setting-up of rare variant association studies. Population-specific exome panels are clearly useful to avoid false positives findings due to population structure and to allow a better understanding of genetic diversity at fine geographic scales.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL