The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts

DSpace/Manakin Repository

The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts

Citable link to this page

 

 
Title: The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts
Author: Saini, Natalie; Roberts, Steven A.; Klimczak, Leszek J.; Chan, Kin; Grimm, Sara A.; Dai, Shuangshuang; Fargo, David C.; Boyer, Jayne C.; Kaufmann, William K.; Taylor, Jack A.; Lee, Eunjung; Cortes-Ciriano, Isidro; Park, Peter J.; Schurman, Shepherd H.; Malc, Ewa P.; Mieczkowski, Piotr A.; Gordenin, Dmitry A.

Note: Order does not necessarily reflect citation order of authors.

Citation: Saini, N., S. A. Roberts, L. J. Klimczak, K. Chan, S. A. Grimm, S. Dai, D. C. Fargo, et al. 2016. “The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts.” PLoS Genetics 12 (10): e1006385. doi:10.1371/journal.pgen.1006385. http://dx.doi.org/10.1371/journal.pgen.1006385.
Full Text & Related Files:
Abstract: Accumulation of somatic changes, due to environmental and endogenous lesions, in the human genome is associated with aging and cancer. Understanding the impacts of these processes on mutagenesis is fundamental to understanding the etiology, and improving the prognosis and prevention of cancers and other genetic diseases. Previous methods relying on either the generation of induced pluripotent stem cells, or sequencing of single-cell genomes were inherently error-prone and did not allow independent validation of the mutations. In the current study we eliminated these potential sources of error by high coverage genome sequencing of single-cell derived clonal fibroblast lineages, obtained after minimal propagation in culture, prepared from skin biopsies of two healthy adult humans. We report here accurate measurement of genome-wide magnitude and spectra of mutations accrued in skin fibroblasts of healthy adult humans. We found that every cell contains at least one chromosomal rearrangement and 600–13,000 base substitutions. The spectra and correlation of base substitutions with epigenomic features resemble many cancers. Moreover, because biopsies were taken from body parts differing by sun exposure, we can delineate the precise contributions of environmental and endogenous factors to the accrual of genetic changes within the same individual. We show here that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts. Trial Registration ClinicalTrials.gov NCT01087307
Published Version: doi:10.1371/journal.pgen.1006385
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082821/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626117
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters