Estimating human replication rate through the analysis of changing maternal/paternal X-chromosome ratios with age in blood cells of females. (A) The percentage dominant allele for 1219 females 18 to 100 years of age. A value of 50% indicates no skewing, and 100% indicates complete skewing. (B-C) Means and percentages of persons with a skewed X-chromosome inactivation ratio (> 75% predominant allele), calculated using bin widths of 10 years. Means instead of the raw data were used to avoid overweighting more frequently occurring ages. (D-F) Percentage of persons with skewing in 3 sets of 100 simulations. For each simulation, we randomly drew replication rates for HSCs expressing the maternal X-chromosome and for HSCs expressing the paternal X-chromosome from a distribution (mean λ), with variance chosen similar to the range observed in Safari cats (Figure 2). The first simulations (D) use λ = 1 per 40 weeks and R₀ (the number of HSCs at birth) = 300. Because R₀ is uncertain, we considered this as a variable. The second set (E) uses λ = 1 per 20 weeks and R₀ = 700, and the third (F) uses λ = 1 per 55 weeks and R₀ = 300. To evaluate the appropriateness of R₀ and λ, we compared the intercepts and slopes (representing value at birth and increase per year of age, respectively) for each of the regressions to the intercepts and slopes of the regressions for 100 sets of 1219 simulations (“Determining acceptable values of λ and R₀”). Fitted regression lines are included. Parameter values in panel D yielded a similar y-intercept and slope to the observed data and were accepted; those in panels E and F did not and were rejected.