@article {Yadav033621, author = {Anupama Yadav and Kaustubh Dhole and Himanshu Sinha}, title = {Phenotypic robustness determines genetic regulation of complex traits}, elocation-id = {033621}, year = {2015}, doi = {10.1101/033621}, publisher = {Cold Spring Harbor Laboratory}, abstract = {A balance between phenotypic variability and robustness is crucial for populations to adapt to multiple selection pressures. The plasticity of genetic pathways underlies this balance. We investigated this plasticity by studying the regulation of phenotypic mean and variance in a biparental recombinant population of Saccharomyces cerevisiae grown in a variety of environments. We found that the growth of this population was well buffered in most environments, such that majority of alleles regulated the mean value of phenotype, and only a subset of these alleles regulated phenotypic variance. This latter class of alleles allowed the other genetic variants to express a range of phenotypic values around a shifted mean. This shift depends on the population and the environment, i.e. based on the evolutionary history of a strain, buffering can result in either a superior or an inferior phenotype in an environment but never both. Interestingly, intricate coupling of the genetic network regulating mean phenotype and robustness was observed in a few environments, which highlighted the importance of phenotypic buffering in layout of the genetic architecture. For loci regulating variance, show a higher tendency of genetic interactions, which not only establishes a genetic basis of release of variance, but also emphasizes the importance of mapping robustness in understanding the network topology of complex traits. Our study demonstrates differential robustness as one of the central mechanisms regulating variation in populations and underlines its role in identifying missing heritability in complex phenotypes and diseases.}, URL = {https://www.biorxiv.org/content/early/2015/12/04/033621}, eprint = {https://www.biorxiv.org/content/early/2015/12/04/033621.full.pdf}, journal = {bioRxiv} }