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Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism
BACKGROUND: The mitochondrial genome (mtDNA) is particularly susceptible to damage mediated by reactive oxygen species (ROS). Although elevated ROS production and elevated biomarkers of oxidative stress have been found in tissues from children with autism spectrum disorders, evidence for damage to m...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570390/ https://www.ncbi.nlm.nih.gov/pubmed/23347615 http://dx.doi.org/10.1186/2040-2392-4-2 |
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author | Napoli, Eleonora Wong, Sarah Giulivi, Cecilia |
author_facet | Napoli, Eleonora Wong, Sarah Giulivi, Cecilia |
author_sort | Napoli, Eleonora |
collection | PubMed |
description | BACKGROUND: The mitochondrial genome (mtDNA) is particularly susceptible to damage mediated by reactive oxygen species (ROS). Although elevated ROS production and elevated biomarkers of oxidative stress have been found in tissues from children with autism spectrum disorders, evidence for damage to mtDNA is lacking. FINDINGS: mtDNA deletions were evaluated in peripheral blood monocytic cells (PBMC) isolated from 2–5 year old children with full autism (AU; n = 67), and typically developing children (TD; n = 46) and their parents enrolled in the CHildhood Autism Risk from Genes and Environment study (CHARGE) at University of California Davis. Sequence variants were evaluated in mtDNA segments from AU and TD children (n = 10; each) and their mothers representing 31.2% coverage of the entire human mitochondrial genome. Increased mtDNA damage in AU children was evidenced by (i) higher frequency of mtDNA deletions (2-fold), (ii) higher number of GC→AT transitions (2.4-fold), being GC preferred sites for oxidative damage, and (iii) higher frequency of G,C,T→A transitions (1.6-fold) suggesting a higher incidence of polymerase gamma incorporating mainly A at bypassed apurinic/apyrimidinic sites, probably originated from oxidative stress. The last two outcomes were identical to their mothers suggesting the inheritance of a template consistent with increased oxidative damage, whereas the frequency of mtDNA deletions in AU children was similar to that of their fathers. CONCLUSIONS: These results suggest that a combination of genetic and epigenetic factors, taking place during perinatal periods, results in a mtDNA template in children with autism similar to that expected for older individuals. |
format | Online Article Text |
id | pubmed-3570390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35703902013-02-13 Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism Napoli, Eleonora Wong, Sarah Giulivi, Cecilia Mol Autism Short Report BACKGROUND: The mitochondrial genome (mtDNA) is particularly susceptible to damage mediated by reactive oxygen species (ROS). Although elevated ROS production and elevated biomarkers of oxidative stress have been found in tissues from children with autism spectrum disorders, evidence for damage to mtDNA is lacking. FINDINGS: mtDNA deletions were evaluated in peripheral blood monocytic cells (PBMC) isolated from 2–5 year old children with full autism (AU; n = 67), and typically developing children (TD; n = 46) and their parents enrolled in the CHildhood Autism Risk from Genes and Environment study (CHARGE) at University of California Davis. Sequence variants were evaluated in mtDNA segments from AU and TD children (n = 10; each) and their mothers representing 31.2% coverage of the entire human mitochondrial genome. Increased mtDNA damage in AU children was evidenced by (i) higher frequency of mtDNA deletions (2-fold), (ii) higher number of GC→AT transitions (2.4-fold), being GC preferred sites for oxidative damage, and (iii) higher frequency of G,C,T→A transitions (1.6-fold) suggesting a higher incidence of polymerase gamma incorporating mainly A at bypassed apurinic/apyrimidinic sites, probably originated from oxidative stress. The last two outcomes were identical to their mothers suggesting the inheritance of a template consistent with increased oxidative damage, whereas the frequency of mtDNA deletions in AU children was similar to that of their fathers. CONCLUSIONS: These results suggest that a combination of genetic and epigenetic factors, taking place during perinatal periods, results in a mtDNA template in children with autism similar to that expected for older individuals. BioMed Central 2013-01-25 /pmc/articles/PMC3570390/ /pubmed/23347615 http://dx.doi.org/10.1186/2040-2392-4-2 Text en Copyright ©2013 Napoli et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Report Napoli, Eleonora Wong, Sarah Giulivi, Cecilia Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism |
title | Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism |
title_full | Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism |
title_fullStr | Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism |
title_full_unstemmed | Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism |
title_short | Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism |
title_sort | evidence of reactive oxygen species-mediated damage to mitochondrial dna in children with typical autism |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570390/ https://www.ncbi.nlm.nih.gov/pubmed/23347615 http://dx.doi.org/10.1186/2040-2392-4-2 |
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