Exact(3)
We thus found a statistically significant correlation between the mean mutant load in each of the five lymphocyte pools and the heteroplasmy distribution at the single-cell level.
The latter indeed showed that, the higher the mean mutant load of a cell pool, the lower the heteroplasmy distribution at the cell level [Petruzzella et al., 1994; Silvestri et al., 2000; Tokunaga et al., 1994].
Although the number of single cells analyzed was low in each pool, we however assumed that each of the 10 cell pools was fairly representative of the whole tissue sample, based on mean mutant load variation consistently less than 10% between the cell pool and the whole sample.
Similar(57)
Thus, assuming that the apparent relationship between mean mutant loads at a whole sample level and mutant load dispersion at the single-cell level makes biological sense in all these tissues, it would remain to be seen whether the proposed tissue dependance of such correlations is valid throughout the 0 100% range of heteroplasmy.
Because mutations such as m.3243A > G exhibit a relatively normal pattern of distribution around the maternal mean, it would be unlikely, given the relatively small sample size and the mean maternal mutant load value in majority below 40% (in blood) in our series (Table 1) to find embryos with greater than 80% heteroplasmy, even in the absence of selection.
Should such a biological process operate prenatally, it could be missed out within the "short" course of a pregnancy, by reference to the very slow decrease of mean mutation level in adult white blood cells [Rajasimha et al., 2008], thus reflecting the apparent intertissue mutant load stability throughout the prenatal period.
MELAS mutant load was quantified using a semiquantitative fluorescent PCR- HaeIII restriction test.
Our data however argue for mutant load stability throughout the entire period of embryofetal development.
The mutant load was calculated by dividing the mutant peak area (73 bp) by the sum of normal (171 bp) and mutant (73 bp) peak areas.
The frequency distribution of a single-cell mutant load within each of the 10 cell pools corresponded to a binomial distribution, with a median value identical or very close to the mean value of heteroplasmy, in keeping with the random genetic drift mechanism.
When pooling mutant loads measured in each embryo from a given woman, mean values were 30 ± 15% and 32 ± 23% for patients 1 and 2, respectively.
Write better and faster with AI suggestions while staying true to your unique style.
Since I tried Ludwig back in 2017, I have been constantly using it in both editing and translation. Ever since, I suggest it to my translators at ProSciEditing.

Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com