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Séminaire

The nature of missing heritability of traits

Dr Joseph SCHACHERER
GMGM, Strasbourg, France

vendredi 29 mars 2019 - 11h00 - Auditorium, IGBMC
Invité(e) par Biologie du développement et cellules souches, Gilles CHARVIN

Understanding the rules laying behind the natural phenotypic variation has been a key point of modern genetics for decades. However, it is still difficult to precisely address and dissect the molecular bases underlying complex traits. Today, a better understanding of the genetic architecture of traits requires a precise estimation of the genetic components governing phenotypes at a species-wide level.
In this context, we took advantage of the large set of 1,011 natural Saccharomyces cerevisiae isolates that we recently sequenced. We selected a set of 55 isolates as genetically diverse as possible to generate a diallel cross panel of 3,025 hybrids. These hybrids were then phenotyped on 49 stress related traits resulting in 148,225 cross/trait combinations. The results clearly showed that although phenotypic variance is mostly governed by additivity, 30% of this variance can be explained by non-additive phenomena. This is confirmed by the fact that a majority of complete dominance is observed in 25% of the traits. The dataset we generated also allowed us to perform genome-wide association studies (GWAS) to uncover variants responsible for the tested phenotypes. Interestingly, 2,156 significantly associated variants were found and among them 12% are present in less than 5% of the 1,011 population. It clearly shows that those so-called rare variants represent an important source of phenotypic variance and can be mapped using GWAS on a diallel panel. To complete this view, we are currently looking at the phenotypic distribution and segregation in the progeny to uncover the phenotypic expressivity variation across genetic backgrounds.

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