Deep sequencing unearths Nuclear mitochondrial Sequences under Leber's hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants
| Autor: | Claudia Calabrese, Teresa Rizza, Silvana Guerriero, Lucia Artuso, Raffaella Trentadue, Anna Maria Porcelli, Giuseppe Gasparre, Rosalba Carrozzo, Marzia Bianchi, Roberta Piredda, Rosa Dell'Aglio, Marcella Attimonelli, Vittoria Petruzzella |
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| Přispěvatelé: | Petruzzella V., Carrozzo R., Calabrese C., Dell'aglio R., Trentadue R., Piredda R., Artuso L., Rizza T., Bianchi M., Porcelli A.M., Guerriero S., Gasparre G., Attimonelli M. |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Proband
Adult Male Mitochondrial DNA Adolescent LEBER'S HEREDITARY OPTIC NEUROPATHY MTDNA MUTATIONS Optic Atrophy Hereditary Leber Biology medicine.disease_cause DNA Mitochondrial Mitochondrial Proteins Young Adult Adenosine Triphosphate Genetics medicine Humans Molecular Biology NUMTS Genetics (clinical) Cell Nucleus Mutation Homoplasmy Electron Transport Complex I Haplotype Leber's hereditary optic neuropathy Temperature High-Throughput Nucleotide Sequencing General Medicine Fibroblasts Middle Aged medicine.disease Penetrance Heteroplasmy Mitochondria Pedigree Female DEEP SEQUENCING DATA Energy Metabolism |
| Popis: | Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or other genetic factors. Discerning between clear-cut pathogenetic variants, such as those that appear to be heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a challenging issue that we have addressed here using next-generation sequencing approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA haplotype, we applied the cybridization protocol. The results demonstrate that the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature of the observed mutations is due to the co-amplification of Nuclear mitochondrial Sequences. |
| Databáze: | OpenAIRE |
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