Combined QTL and selective sweep mappings with coding SNP annotation and cis-eQTL analysis revealed PARK2 and JAG2 as new candidate genes for adiposity regulation.
Bottom Line: Using new haplotype-based statistics exploiting the very high SNP density generated through whole-genome resequencing, we found 129 significant selective sweeps.We then focused on two of these QTL/sweeps.This study shows for the first time the interest of combining selective sweeps mapping, coding SNP annotation and cis-eQTL analyses for identifying causative genes for a complex trait, in the context of divergent lines selected for this specific trait.
Affiliation: INRA, UMR1348 Pegase, Saint-Gilles, 35590, France Agrocampus Ouest, UMR1348 Pegase, Rennes, 35000, France Université Européenne de Bretagne, France.Show MeSH
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Mentions: In our experimental design, the analysis of colocalization of QTL and selective sweeps markedly shortened the list of candidate genes in each region, sometimes even down to one, making the latter a strong causative positional candidate. We therefore focused on two genes, each located in two distinct QTL colocalizing with different selective sweep patterns. The absence of missense and nonsense SNP on those genes strongly suggested that their expression should be regulated in cis. We thus confirmed cis regulation in chicken or mice models, contrasted for adiposity by analyzing ASE (chicken) or GWAS (mice). These observations therefore strengthen positional and also functional status of those genes. By combining these complementary approaches, summarized in Figure 1, we identified two strong positional and functional candidate genes underlying AF QTL, including one previously unknown to be involved in the genetic control of adiposity.
Affiliation: INRA, UMR1348 Pegase, Saint-Gilles, 35590, France Agrocampus Ouest, UMR1348 Pegase, Rennes, 35000, France Université Européenne de Bretagne, France.