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Systems Biology Programme Dr. Richard Mott

Systems Biology Programme Dr. Richard MottSystems Biology Programme Dr. Richard Mott

03/02/2023
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Systems Biology Programme Dr. Richard Mott

MARIE CURIE

03/02/202310:00MARIE CURIESystems Biology ProgrammeDr. Richard MottGenetic Institute, University College London"Dominance in Mammalian phenotypes and gene expression"Host: Baud, AmelieAbstract:Dominance in Mammalian phenotypes and gene expression

Richard Mott
Genetic Institute
University College London

Dominance arises from the interaction between different alleles within the same genomic locus, and historically played a major role in quantitative genetics. However, today most genome-wide association studies (GWAS) ignore dominance effects and assume alleles act additively. Here, we systematically investigated both dominance and additive effects across numerous physiological and gene expression traits of three mammalian model populations: a Pig F2 Intercross, a Rat Heterogeneous Stock and a Mouse Heterogeneous Stock. In all three species, and across 574 physiological traits, dominance variance accounts for about one quarter of the total heritable variance. Hematological and immunological traits generally present a high dominance variance, possibly reflecting balancing selection as a response to rapidly evolving pathogens. We identified 154, 64 and 62 novel dominance QTLs in pigs, rats and mice respectively, that were missed by additive GWAS. For expression traits, we observed a surprisingly larger fraction of dominance variance across all species, even though most cis-eQTLs are additive, because trans-acting eQTLs are enriched for dominance effects. As a result, genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead are associated via trans-acting dominance eQTLs. In addition, in HS rat transcriptomes, we found 5,489 genes containing eQTLs for alternate transcripts with mixed additive and dominant architectures, thereby suggesting a mechanism for dominance.