Similarly, we detected significantly larger deletion spans in the adaptive recovery populations compared to spontaneous deletions occurring under mutation accumulation conditions (Wilcoxon two-sample test, Z = −2.4, p = 0.016, Fig. 3b).
The duplication span in our adaptive recovery populations is significantly greater than that of previously determined spontaneous duplications under mutation accumulation conditions [ 8] (Wilcoxon two-sample test, Z = −3.85, p < 0.0001, Fig. 3a).
Further tests of the hypothesis of mutation accumulation might more fruitfully focus on diseases 1) epidemiologically characterized by a very late and/or less variable age of onset and/or 2) with an abundance of common and ancient alleles.
The theory underlying the mutation accumulation assay is that all mutations other than lethal mutations accumulate as if neutral.
Since we were unable to define a common set of mutation parameters that would recapitulate the experimentally observed mutation accumulation rates, somatic evolution/leukemia incidence, and HSC fitness decline with age, we tested an alternative, evolutionary model.
Between-line variability in the rate of mutation accumulation.
Blokzijl, F. et al. Tissue-specific mutation accumulation in human adult stem cells during life.
Albin, R. L. Antagonistic pleiotropy, mutation accumulation, and human genetic disease.
These cells are maintained throughout life, increasing the opportunities for mutation accumulation.
BRCA1 is therefore not a good candidate for mutation accumulation.
