Dear all,
The next seminar in our series of statistics talks for people interested in quantitative methods in biology and medicine will take place on Thursday 19 January 2017 at 15:00 (unusual time!), in the Salle Delachaux (Biopôle 2, first floor, Route de la Corniche 10, 1010 Lausanne, M2: Vennes).
The speaker will be Dr. Konstantin Popadin (Centre for Integrative Genomics, University of Lausanne)
Title: Main targets of the negative selection in the human genome
Abstract: All organisms harbor many slightly-deleterious (SD) variants in their genomes. For example, every human genome has approximately one thousand point SD coding variants, several thousand point SD regulatory variants, and dozens of SD copy number variants. Even though most of these mutations individually have small effects, their cumulative effect (mutation load) is expected to affect health status and reduce the fitness of an individual. Thus the mutational load is assumed to be one of the most important targets of selection. Despite the fundamental importance of this assumption (causative relationship between the load and fitness) it is still a hypothesis. The biggest problem is that the composition of the load is extremely complex and poorly known (thousands of SD mutations with different and very small individual phenotypic effects interacting with each other in additive or epistatic ways) and its effect on the fitness is noisy and hidden. In this project I would like to uncover a link between the mutational load and the fitness considering organisms under very severe conditions (hereafter the 'genetic handicap') where this predicted functional relationship between the load and viability (one of the most important components of fitness) can be stronger. I hypothesize that the severe conditions (genetic handicap) can interact with the load of SD variants in a specific way which makes the effect of each slightly-deleterious variant much more severe and thus much more detectable for selection. In my project I would like to test this statement from several points of view: theoretical (population genetic model and simulations), empirical (analyzes of live-born Down Syndrome individuals and carriers of rare deletions) and experimental (introduced genetic handicap into model species). Using the genetic handicap approach it will be possible to investigate deeply the mutation loads of human and model organisms.
Happy new year and hope to see you there!
Valentin
(for the organizers: Jérôme Goudet, Valentin Rousson, Frédéric Schütz)
