6533b826fe1ef96bd1284ea0

RESEARCH PRODUCT

La combinaison de cartographie de signatures de sélection, de re-séquençage de génomes et d'analyses d'expression révèle PARK2 et JAG2 comme nouveaux genes candidats régulant l'adiposité

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Very few causal genes have been identified by quantitative trait loci (QTLs) mapping because of the large size ofQTLs, and most of them were identified thanks to functional links already known with the targeted phenotype.Here we propose to combine selection signature detection, SNP annotation, and expression analyses to identifycausal genes underlying QTLs. As a model, we chose experimental chicken lines divergently selected for onlyone trait, the abdominal fat weight, in which several QTLs were previously mapped. Using a new haplotypebasedstatistics exploiting the very high SNP density generated through whole genome re-sequencing, we found129 significant selective sweeps. Most of the QTLs co-localized with at least one sweep, which markedlynarrowed candidate region size. Some of those sweeps contained only one gene, therefore making them strongpositional causal candidates with no presupposed function. We then focused on two of these QTLs/sweeps. Theabsence of non-synonymous SNP in their coding regions strongly suggests the existence of causal mutationsacting in cis on their expression, confirmed for one of both. Additional expression analyses on those two genesin the divergent chicken lines and in genetically diverse mice contrasted for adiposity confirm their link with thisphenotype. This study shows for the first time the interest of using selective sweeps combined with SNPs andexpression analyses in divergent lines selected for a specific trait for identifying causative genes and highlightstwo genes, JAG2 and PARK2, as new potential negative and positive key regulators of adiposity in chicken andmice.