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The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts
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نویسنده
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saini n. ,roberts s.a. ,klimczak l.j. ,chan k. ,grimm s.a. ,dai s. ,fargo d.c. ,boyer j.c. ,kaufmann w.k. ,taylor j.a. ,lee e. ,cortes-ciriano i. ,park p.j. ,schurman s.h. ,malc e.p. ,mieczkowski p.a. ,gordenin d.a.
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منبع
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plos genetics - 2016 - دوره : 12 - شماره : 10
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چکیده
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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 © 2016 public library of science. all rights reserved.
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آدرس
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genome integrity and structural biology laboratory,national institute of environmental health sciences,us national institutes of health,research triangle park,nc, United States, school of molecular biosciences,washington state university,pullman,wa, United States, integrative bioinformatics support group,national institute of environmental health sciences,us national institutes of health,research triangle parknc, United States, genome integrity and structural biology laboratory,national institute of environmental health sciences,us national institutes of health,research triangle park,nc, United States, integrative bioinformatics support group,national institute of environmental health sciences,us national institutes of health,research triangle parknc, United States, integrative bioinformatics support group,national institute of environmental health sciences,us national institutes of health,research triangle parknc, United States, integrative bioinformatics support group,national institute of environmental health sciences,us national institutes of health,research triangle parknc, United States, department of environmental science and engineering,university of north carolina,chapel hill,nc, United States, department of pathology and laboratory medicine,university of north carolina,chapel hill,nc, United States, epidemiology branch,national institute of environmental health sciences,us national institutes of health,research triangle park,nc, United States, department of biomedical informatics,harvard medical school,boston,ma,united states,division of genetics,brigham and women’s hospital,boston,ma, United States, department of biomedical informatics,harvard medical school,boston,ma, United States, department of biomedical informatics,harvard medical school,boston,ma,united states,division of genetics,brigham and women’s hospital,boston,ma, United States, clinical research unit,national institute of environmental health sciences,us national institutes of health,research triangle park,nc, United States, department of genetics,lineberger comprehensive cancer center,university of north carolina,chapel hill,nc, United States, department of genetics,lineberger comprehensive cancer center,university of north carolina,chapel hill,nc, United States, genome integrity and structural biology laboratory,national institute of environmental health sciences,us national institutes of health,research triangle park,nc, United States
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Authors
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