DOI: 10.1101/471342Nov 18, 2018Paper

Early divergence of mutational mechanisms drives genetic heterogeneity of fetal tissues

BioRxiv : the Preprint Server for Biology
Ewart KuijkEdwin Cuppen

Abstract

A developing human fetus needs to balance rapid cellular expansion with maintaining genomic stability. Here, we accurately quantified and characterized somatic mutation accumulation in fetal tissues by analyzing individual stem cells from human fetal liver and intestine. Fetal mutation rates were ~5-fold higher than in tissue-matched adult stem cells. The mutational landscape of fetal intestinal stem cells resembled that of adult intestinal stem cells, while the mutation spectrum of fetal liver stem cells is distinct from stem cells of the fetal intestine and the adult liver. Our analyses indicate that variation in mutational mechanisms, including oxidative stress and spontaneous deamination of methylated cytosines, contribute to the observed divergence in mutation accumulation patterns and drive genetic mosaicism in humans.

Related Concepts

Cell Growth
Cytosine
Fetus
Intestines
Liver
Stem Cells
Fetal Tissue
Oxidative Stress
Patterns
Intestinal Cell

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