Registro completo de metadatos
| Campo DC | Valor | Lengua/Idioma |
|---|---|---|
| dc.creator | Sookoian, Silvia Cristina | - |
| dc.creator | Flichman, Diego Martin | - |
| dc.creator | Scian, Romina | - |
| dc.creator | Rohr, Cristian Oscar | - |
| dc.creator | Dopazo, Hernán Javier | - |
| dc.creator | Fernández Gianotti, Tomás | - |
| dc.creator | San Martino, Julio | - |
| dc.creator | Castaño, Gustavo Osvaldo | - |
| dc.creator | Pirola, Carlos José | - |
| dc.date | 2018-06-05T13:28:11Z | - |
| dc.date | 2018-06-05T13:28:11Z | - |
| dc.date | 2016-12 | - |
| dc.date | 2018-06-04T17:03:42Z | - |
| dc.date.accessioned | 2019-04-29T15:50:27Z | - |
| dc.date.available | 2019-04-29T15:50:27Z | - |
| dc.date.issued | 2016-12 | - |
| dc.identifier | Sookoian, Silvia Cristina; Flichman, Diego Martin; Scian, Romina; Rohr, Cristian Oscar; Dopazo, Hernán Javier; et al.; Mitochondrial genome architecture in non-alcoholic fatty liver disease; John Wiley & Sons Ltd; Journal of Pathology; 240; 4; 12-2016; 437-449 | - |
| dc.identifier | 0022-3417 | - |
| dc.identifier | http://hdl.handle.net/11336/47275 | - |
| dc.identifier | CONICET Digital | - |
| dc.identifier | CONICET | - |
| dc.identifier.uri | http://rodna.bn.gov.ar:8080/jspui/handle/bnmm/303433 | - |
| dc.description | Non‐alcoholic fatty liver disease (NAFLD) is associated with mitochondrial dysfunction, a decreased liver mitochondrial DNA (mtDNA) content, and impaired energy metabolism. To understand the clinical implications of mtDNA diversity in the biology of NAFLD, we applied deep‐coverage whole sequencing of the liver mitochondrial genomes. We used a multistage study design, including a discovery phase, a phenotype‐oriented study to assess the mutational burden in patients with steatohepatitis at different stages of liver fibrosis, and a replication study to validate findings in loci of interest. We also assessed the potential protein‐level impact of the observed mutations. To determine whether the observed changes are tissue‐specific, we compared the liver and the corresponding peripheral blood entire mitochondrial genomes. The nuclear genes POLG and POLG2 (mitochondrial DNA polymerase‐γ) were also sequenced. We observed that the liver mtDNA of patients with NAFLD harbours complex genomes with a significantly higher mutational (1.28‐fold) rate and degree of heteroplasmy than in controls. The analysis of liver mitochondrial genomes of patients with different degrees of fibrosis revealed that the disease severity is associated with an overall 1.4‐fold increase in mutation rate, including mutations in genes of the oxidative phosphorylation (OXPHOS) chain. Significant differences in gene and protein expression patterns were observed in association with the cumulative number of OXPHOS polymorphic sites. We observed a high degree of homology (∼98%) between the blood and liver mitochondrial genomes. A missense POLG p.Gln1236His variant was associated with liver mtDNA copy number. In conclusion, we have demonstrated that OXPHOS genes contain the highest number of hotspot positions associated with a more severe phenotype. The variability of the mitochondrial genomes probably originates from a common germline source; hence, it may explain a fraction of the ‘missing heritability’ of NAFLD. | - |
| dc.description | Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina | - |
| dc.description | Fil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina | - |
| dc.description | Fil: Scian, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina | - |
| dc.description | Fil: Rohr, Cristian Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina | - |
| dc.description | Fil: Dopazo, Hernán Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina | - |
| dc.description | Fil: Fernández Gianotti, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina | - |
| dc.description | Fil: San Martino, Julio. Hospital Diego Thompson; Argentina | - |
| dc.description | Fil: Castaño, Gustavo Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina | - |
| dc.description | Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina | - |
| dc.format | application/pdf | - |
| dc.format | application/pdf | - |
| dc.format | application/pdf | - |
| dc.format | application/pdf | - |
| dc.format | application/pdf | - |
| dc.format | application/pdf | - |
| dc.language | eng | - |
| dc.publisher | John Wiley & Sons Ltd | - |
| dc.relation | info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1002/path.4803 | - |
| dc.relation | info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/path.4803 | - |
| dc.rights | info:eu-repo/semantics/restrictedAccess | - |
| dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | - |
| dc.source | reponame:CONICET Digital (CONICET) | - |
| dc.source | instname:Consejo Nacional de Investigaciones Científicas y Técnicas | - |
| dc.source | instacron:CONICET | - |
| dc.subject | MITOCHONDRIAL GENOME | - |
| dc.subject | NGS | - |
| dc.subject | NAFLD | - |
| dc.subject | GENOMICS | - |
| dc.subject | Inmunología | - |
| dc.subject | Medicina Básica | - |
| dc.subject | CIENCIAS MÉDICAS Y DE LA SALUD | - |
| dc.title | Mitochondrial genome architecture in non-alcoholic fatty liver disease | - |
| dc.type | info:eu-repo/semantics/article | - |
| dc.type | info:eu-repo/semantics/publishedVersion | - |
| dc.type | info:ar-repo/semantics/articulo | - |
| Aparece en las colecciones: | CONICET | |
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