Table 2.

Somatic mutation types, loads and spectra detected in healthy human cells.

Somatic Variation	Tissue type analyzed	Load and spectra of somatic changes	Methodology used	Reference
Copy number changes	Brain	Large CNVs > 1Mb can occur in 13–41% of neurons from healthy individuals and hemimegalencephaly patients.	Single cell sequencing and single cell SNP arrays	(Cai et al., 2014; McConnell et al., 2013)
	Skin	Approximately 30% skin fibroblasts have megabase-scale CNVs	iPSCs sequencing	(Abyzov et al., 2012)
	Skin and brain	8–9% of the cells have at least 1 megabase-scale CNV	Single cell sequencing	(Knouse et al., 2016; Knouse et al., 2014)
	Skin	Skin fibroblasts have at least 1 somatic CNV, and ~30% cells have megabase-scale CNVs. Most CNVs are near known fragile genomic regions.	Single-cell-derived clonal lineage sequencing	(Saini et al., 2016)
Structural Variations	Skin	All skin fibroblasts have at least 1 somatic structural variation. Deletions are the most abundant SV, however duplications, inversions and translocations were detected in the cells. Most SVs are near known fragile genomic regions.	Single-cell-derived clonal lineage sequencing	(Saini et al., 2016)
Retrotransposition	Brain	<0.6 somatic L1 retrotransposition events detected per neuron	Single cell sequencing	(Evrony et al., 2012)
Single base substitutions	Skin	3760 mutations found across the 234 samples from four individuals. Prevalence of C→T and CC→TT changes characteristic of UV-induced mutations	Deep sequencing of 74 genes from eyelid biopsies	(Martincorena et al., 2015)
	Brain	~1500 somatic mutations per neuron. The major mutation signature was C→T changes at CpG motifs.	Single cell sequencing	(Lodato et al., 2015)
	Skin	~600 to 13000 somatic mutations per skin fibroblast obtained from skin biopsies from the hips and forearms. Mutation load in sun-exposed skin is higher, with a prevalence of UV-mutation signature.	Single-cell-derived clonal lineage sequencing	(Saini et al., 2016)
	Skin	~1000 somatic mutations per skin fibroblast obtained from donor underarm skin biopsy.	iPSCs sequencing	(Abyzov et al., 2017)
	Skin and Blood	14 to 28 somatic mutations in protein coding genes and 391 somatic changes in endothelial progenitor cells from one 57 year old individual.	iPSCs and monoclonal EPCs sequencing	(Rouhani et al., 2016)
	Brain	200–400 somatic mutations in neurons from 12–14 week old fetus. C→T changes at CpG motifs and C→A changes characteristic of oxidative damage were the prevalent mutation signatures.	Single-cell-derived clonal lineage sequencing	(Bae et al., 2018)
	Colon, small intestine and liver	1000–3000 mutations per cell. Linear increase in mutation loads with age. C→T changes at CpG motif detected in small intestine and colon cells. Mutation signature attributable to an unknown source in liver cells.	Adult stem cells-derived organoids sequencing	(Blokzijl et al., 2016)