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Title: One thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin      
dateReleased:
02-08-2017
privacy:
information not avaiable
aggregation:
instance of dataset
dateCreated:
02-08-2017
refinement:
curated
ID:
doi:10.15154/1342749
creators:
Vaccarino, Flora
Abyzov, Alexej
Tomasini, Livia
Zhou, Bo
Vasmatzis, Nikolaos
Coppola, Gianfilippo
Amenduni, Mariangela
Pattni, Reenal
Wilson, Michael
Gerstein, Mark
Weissman, Sherman
Urban, Alexander
availability:
available
types:
other
description:
Few studies have been conducted to understand post-zygotic accumulation of mutations in cells of the healthy human body. We reprogrammed 32 skin fibroblast cells from families of donors into human induced pluripotent stem cell (hiPSC) lines. The clonal nature of hiPSC lines allows a high-resolution analysis of the genomes of the founder fibroblast cells without being confounded by the artifacts of single cell whole genome amplification. We estimate that on average a fibroblast cell in children has 1,035 mostly benign mosaic SNVs. On average, 235 SNVs could be directly confirmed in the original fibroblast population by ultra-deep sequencing, down to an allele frequency (AF) of 0.1%. More sensitive droplet digital PCR experiments confirmed more SNVs as mosaic with AF as low as 0.01%, suggesting that 1,035 mosaic SNVs per fibroblast cell is the true average. Similar analyses in adults revealed no significant increase in the number of SNVs per cell, suggesting that a major fraction of mosaic SNVs in fibroblasts arises during development. Mosaic SNVs were distributed uniformly across the genome and were enriched in a mutational signature previously observed in cancers and in de novo variants and which, we hypothesize, is a hallmark of normal cell proliferation. Finally, AF distribution of mosaic SNVs had distinct narrow peaks, which could be a characteristic of clonal cell selection, clonal expansion, or both. These findings reveal a large degree of somatic mosaicism in healthy human tissues, link de novo and cancer mutations to somatic mosaicism and couple somatic mosaicism with cell proliferation.
accessURL: https://doi.org/10.15154/1342749
storedIn:
NIMH Data Archives
qualifier:
not compressed
format:
HTML
accessType:
landing page
authentication:
none
authorization:
none
abbreviation:
NIH
homePage: http://www.nih.gov/
ID:
SCR:011417
name:
National Institutes of Health
abbreviation:
NIMH
homePage: http://www.nimh.nih.gov/
ID:
SCR:011431
name:
National Institute of Mental Health

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