{"616209":{"#nid":"616209","#data":{"type":"event","title":"The Contribution of DNA Damage and Repair to Genome-wide Human Somatic Mutation Loads","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003ENatalie Saini, \u003C\/strong\u003E\u003Cstrong\u003EPh.D\u003C\/strong\u003E\u003Cstrong\u003E.\u003Cbr \/\u003E\r\nNational Institute of Environmental Health Sciences\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EABSTRACT\u003C\/strong\u003E\u003Cbr \/\u003E\r\nAccumulation of somatic mutations over the lifetime of an individual can be facilitated by genetic factors like impaired DNA repair pathways, and by exogenous DNA damaging agents.\u0026nbsp; The large-scale cancer genome sequencing projects have demonstrated that mutation load and spectra in cancer genomes are characteristic of the cell and type tissue, location in the body, and environmental exposures.\u0026nbsp; However, accurate measurements of lifetime accumulation of genetic changes attributable to these factors in healthy human cells are lacking.\u0026nbsp; Previously, we demonstrated that mutation loads and spectra in the genomes of single skin fibroblast-derived clonal lineages from two healthy individuals resemble cancers.\u0026nbsp; We showed that while, all samples carry C\u0026agrave;T changes at CpG dinucleotides (the aging-associated mutation signature), cells from sun-exposed body sites carry a higher mutation burden with a predominant UV\u0026ndash;induced mutation signature as compared to unexposed sites.\u0026nbsp; Somatic mutation load also can be used as a measure of the ability of the cells to repair lesions.\u0026nbsp; As such, we hypothesize that individuals with potentially deleterious polymorphisms in DNA repair genes, would have higher mutation loads and different mutational spectra than carriers of functional alleles.\u0026nbsp; We have obtained DNA from \u0026gt;3000 individuals via the NIEHS Environmental Polymorphisms Registry.\u0026nbsp; Amplification of potential DNA repair genes with asymmetric barcodes, and sequencing via the Pacific Biosciences single molecule real-time sequencing technology is used for identifying healthy individuals with common and rare deleterious alleles in the given gene.\u0026nbsp; Sequencing single cell-derived clones from these individuals provides the range of mutation loads, and predominant mutation signatures attributable to defects in DNA repair pathways across a population.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EHost: Kirill Lobachev, Ph.D.\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"A Biological Sciences Seminar by Natalie Saini, Ph.D."}],"uid":"27964","created_gmt":"2019-01-10 17:58:01","changed_gmt":"2019-01-10 17:58:01","author":"Jasmine Martin","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2019-03-21T11:55:00-04:00","event_time_end":"2019-03-21T11:55:00-04:00","event_time_end_last":"2019-03-21T11:55:00-04:00","gmt_time_start":"2019-03-21 15:55:00","gmt_time_end":"2019-03-21 15:55:00","gmt_time_end_last":"2019-03-21 15:55:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"1275","name":"School of Biological Sciences"}],"categories":[],"keywords":[{"id":"68181","name":"Natalie Saini"},{"id":"8668","name":"Kirill Lobachev"},{"id":"166892","name":"School of Biological Sciences Seminar"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"177814","name":"Postdoc"},{"id":"78771","name":"Public"},{"id":"174045","name":"Graduate students"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:jasmine.martin@biosci.gatech.edu\u0022\u003EJasmine Martin\u003C\/a\u003E\u003C\/p\u003E\r\n","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}