Estimation of negative selection acting on aneuploid cells in normal human fibroblasts.

<p>(A) Chiron-based simulation (20 parallel runs) of a growing cell population with a mis-segregation rate of 4×10⁻⁴ where different degrees of selection (<i>s</i>) against aneuploid cells are imposed. The resulting mean prevalence values of cells aneusomic (non-disomic) for a certain chromosome are given as aneusomy indices (AI) on the y-axis. AI is reduced with higher <i>s</i> values and reaches a dynamic equilibrium around 25 generations even at selection values as low as 10%. (B) Relationship of mean AI for a certain chromosome and negative selection acting on cells with aneusomy for this chromosome. Red lines correspond to estimations of selection made from experimental data for chromosomes 1 and 17 in F1 and F2. Error bars correspond to standard deviations in 20 simulations. (C) Fluorescence <i>in situ</i> hybridisation (FISH) was used to estimate AI in human normal fibroblasts, exemplified by F1 cells disomic (2n) and trisomic (3n) for chromosome 17 (red, q arm probe signal; blue, centromeric signal). (D) Prevalence of monosomic and trisomic cells as well as overall AI estimated by FISH in the two fibroblast lines F1 and F2. (E) Chiron-based estimates of the degree of negative selection acting on cells aneusomic for chromosomes 2 and 17 in F1 and F2, deduced by comparing FISH-data (AI) with modelling of AI as a function of <i>s</i> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070445#pone-0070445-g003" target="_blank">Figure 3B</a>). The max and min values correspond to ±2 standard deviations.