Fig. 1: Early developmental cell lineages in the mother (NC0) and post-zygotic mutations tranmitted to the offspring.
A Identifiers and relationship between 4 individuals (mother in orange; father in blue; two children in green and purple, respectvely) are shown in the pedigree for the sequenced family. B Body outline of NC0 (created with BioRender.com) shows location of biopsies used to derive iPSC lines from skin fibroblasts. C Cell lineage ancestry of NC0, which was originally reconstructed in our previous study5. Mutations shared by descendant cells are denoted by Latin and Greek letters including 4 indels (m, o, κ, λ). One branch has ten mutations and they are not denoted individually rather represented by a number. Mutations that were transmitted to NC0-1 and NC0-2 are highlighted in green and purple circles respectively. The corresponding cell lineages that bear the mutations transmitted to daughters are colored accordingly. For each branch in transmitted lineages, bar graphs show mean cell frequencies (corresponding percentages are indicated) of corresponding mutations in bulk blood (red), saliva (blue), and urine (yellow) in logarithmic scale. The squared plot shows correlations between the mutation cell frequencies (average across corresponding mutations; linear scale) in the three bulk samples for the dominant (y-axis: range 0 to 100%) and the recessive (x-axis: range 0 to 100%) lineages and their biased contribution to blood, saliva, urine (i.e., shifted away from the star which indicates equal contribution). The location of the dots along the dashed diagonal means that the sum of frequencies for dominant and recessive lineage is 100%, i.e., the division is likely fully captured, and all cells in analyzed tissues are progenies of the first two blastomeres. Diamonds depict founder germ cells (FGCs). The terminal of the branches represents the sampled clonal iPSC lines. D Variant Allele Frequencies (VAFs) in each child for all transmitted post-zygotic mosaic mutations in (C). E, F For the most recent ancestral cell (marked by “*”) traceable for the germline lineage that led to each offspring, alternative branches other than those shown in (C) are equally possible as shown in (E) for NC0-1 and (F) for NC0-2. Source data are provided in Supplementary Data 1 and 2.
