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dc.contributor.author Haugen, AC
dc.contributor.author Di Prospero, NA
dc.contributor.author Parker, JS
dc.contributor.author Fannin, RD
dc.contributor.author Chou, J
dc.contributor.author Meyer, JN
dc.contributor.author Halweg, C
dc.contributor.author Collins, JB
dc.contributor.author Durr, A
dc.contributor.author Fischbeck, K
dc.contributor.author Van Houten, B
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:16Z
dc.date.issued 2010-01-15
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20090835
dc.identifier.citation PLoS Genet, 2010, 6 (1), pp. e1000812 - ?
dc.identifier.uri http://hdl.handle.net/10161/4460
dc.description.abstract The neurodegenerative disease Friedreich's ataxia (FRDA) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene. In this disease, transcription of frataxin, a mitochondrial protein involved in iron homeostasis, is impaired, resulting in a significant reduction in mRNA and protein levels. Global gene expression analysis was performed in peripheral blood samples from FRDA patients as compared to controls, which suggested altered expression patterns pertaining to genotoxic stress. We then confirmed the presence of genotoxic DNA damage by using a gene-specific quantitative PCR assay and discovered an increase in both mitochondrial and nuclear DNA damage in the blood of these patients (p<0.0001, respectively). Additionally, frataxin mRNA levels correlated with age of onset of disease and displayed unique sets of gene alterations involved in immune response, oxidative phosphorylation, and protein synthesis. Many of the key pathways observed by transcription profiling were downregulated, and we believe these data suggest that patients with prolonged frataxin deficiency undergo a systemic survival response to chronic genotoxic stress and consequent DNA damage detectable in blood. In conclusion, our results yield insight into the nature and progression of FRDA, as well as possible therapeutic approaches. Furthermore, the identification of potential biomarkers, including the DNA damage found in peripheral blood, may have predictive value in future clinical trials.
dc.format.extent e1000812 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS Genet
dc.relation.isversionof 10.1371/journal.pgen.1000812
dc.subject Adolescent
dc.subject Adult
dc.subject Cells, Cultured
dc.subject Child
dc.subject Cohort Studies
dc.subject DNA Damage
dc.subject Female
dc.subject Friedreich Ataxia
dc.subject Gene Expression
dc.subject Humans
dc.subject Iron-Binding Proteins
dc.subject Male
dc.subject Middle Aged
dc.subject RNA
dc.subject Young Adult
dc.title Altered gene expression and DNA damage in peripheral blood cells from Friedreich's ataxia patients: cellular model of pathology.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-1-0 en_US
duke.description.endpage e1000812 en_US
duke.description.issue 1 en_US
duke.description.startpage e1000812 en_US
duke.description.volume 6 en_US
dc.relation.journal Plos Genetics en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20090835
pubs.issue 1
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/Initiatives
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/Initiatives/Energy Initiative
pubs.organisational-group /Duke/Nicholas School of the Environment
pubs.organisational-group /Duke/Nicholas School of the Environment/Environmental Sciences and Policy
pubs.organisational-group /Duke/Pratt School of Engineering
pubs.organisational-group /Duke/Pratt School of Engineering/Civil and Environmental Engineering
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published online
pubs.volume 6
dc.identifier.eissn 1553-7404

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