UNIVERSITY OF SOUTHERN CALIFORNIA

M O L E C U L A R & C O M P U TAT I O NA L B I O LO G Y
COLLOQUIUM SERIES

Joe Nadeau, PhD

Center for Molecular Medicine,
Maine Medical Center, Portland

will present on
“Noise, the Third
Dimension of Phenotypic
Variation in Health and
Disease”

Abstract:
Phenotypes are often noisy, sometimes varying dramatically, even among
genetically identical individuals in standardized conditions. Dogma argues that
genetics (G) and environment (E), acting in a deterministic and linear manner, are
the primary determinants of phenotypes (P). Unaccounted phenotypic variation is
considered to be residual (R), where R usually includes only undetected G,
Friday, unmeasured E, measurement error, and irreducible variation. Largely ignored is
February 07, 2020 the increasing evidence that a third factor – ‘Noise’ (N) – contributes significantly
12:00 pm to 1:00 pm through as-yet ill-defined regulatory mechanisms. Various considerations suggest
that R results largely from N and that P = G + E + N.

Ray R. Irani Hall We propose that the input for Noise - epigenetic change - is transient, stochastic
and therefore probabilistic during development, while its often non-linear output -
1050 Childs Way, RRI
alternative phenotypic states – endures, impacting health and disease across a
101 lifetime. After the window of epigenetic vulnerability has passed, each decision is
fixed, thus generating a stable but distinct phenotypic trajectory. These epigenetic
For additional information, triggers and functional targets are experimentally tractable, especially with our
unique mouse mutants, pioneering Chromosome Substitution Strains, and novel
contact:
analytical methods that focus on both variation and mean effects. Indeed, ongoing
Ian Ehrenreich work has identified the first epigenetic mediators as well as candidate targets in
ehrenrei@usc.edu diet-induced metabolic conditions.

Uluwehi Baldmor The strong evidence in humans and mouse models suggest that Noise accounts for
baldmore@usc.edu as much as 50% of phenotypic variation. An understanding of the mechanistic
origins of this surprisingly large and neglected dimension is essential to understand
organismal biology and to achieve the goals of precision medicine.