Mitochondrial genome analysis of primary open angle glaucoma patients.

Primary open angle glaucoma (POAG) is a multi-factorial optic disc neuropathy characterized by accelerating damage of the retinal ganglion cells and atrophy of the optic nerve head. The vulnerability of the optic nerve damage leading to POAG has been postulated to result from oxidative stress and mi...

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Autores principales:	Deblina Banerjee, Antara Banerjee, Suddhasil Mookherjee, Mansi Vishal, Arijit Mukhopadhyay, Abhijit Sen, Analabha Basu, Kunal Ray
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa1ee968be30473ebf15d4a30dd73bb6
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spelling	oai:doaj.org-article:fa1ee968be30473ebf15d4a30dd73bb62021-11-18T09:01:16ZMitochondrial genome analysis of primary open angle glaucoma patients.1932-620310.1371/journal.pone.0070760https://doaj.org/article/fa1ee968be30473ebf15d4a30dd73bb62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23940637/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Primary open angle glaucoma (POAG) is a multi-factorial optic disc neuropathy characterized by accelerating damage of the retinal ganglion cells and atrophy of the optic nerve head. The vulnerability of the optic nerve damage leading to POAG has been postulated to result from oxidative stress and mitochondrial dysfunction. In this study, we investigated the possible involvement of the mitochondrial genomic variants in 101 patients and 71 controls by direct sequencing of the entire mitochondrial genome. The number of variable positions in the mtDNA with respect to the revised Cambridge Reference Sequence (rCRS), have been designated "Segregating Sites". The segregating sites present only in the patients or controls have been designated "Unique Segregating Sites (USS)". The population mutation rate (θ = 4Neμ) as estimated by Watterson's θ (θw), considering only the USS, was significantly higher among the patients (p = 9.8 × 10(-15)) compared to controls. The difference in θw and the number of USS were more pronounced when restricted to the coding region (p<1.31 × 10(-21) and p = 0.006607, respectively). Further analysis of the region revealed non-synonymous variations were significantly higher in Complex I among the patients (p = 0.0053). Similar trends were retained when USS was considered only within complex I (frequency 0.49 vs 0.31 with p<0.0001 and mutation rate p-value <1.49×10(-43)) and ND5 within its gene cluster (frequency 0.47 vs 0.23 with p<0.0001 and mutation rate p-value <4.42×10(-47)). ND5 is involved in the proton pumping mechanism. Incidentally, glaucomatous trabecular meshwork cells have been reported to be more sensitive to inhibition of complex I activity. Thus mutations in ND5, expected to inhibit complex I activity, could lead to generation of oxidative stress and favor glaucomatous condition.Deblina BanerjeeAntara BanerjeeSuddhasil MookherjeeMansi VishalArijit MukhopadhyayAbhijit SenAnalabha BasuKunal RayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70760 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Deblina Banerjee Antara Banerjee Suddhasil Mookherjee Mansi Vishal Arijit Mukhopadhyay Abhijit Sen Analabha Basu Kunal Ray Mitochondrial genome analysis of primary open angle glaucoma patients.
description	Primary open angle glaucoma (POAG) is a multi-factorial optic disc neuropathy characterized by accelerating damage of the retinal ganglion cells and atrophy of the optic nerve head. The vulnerability of the optic nerve damage leading to POAG has been postulated to result from oxidative stress and mitochondrial dysfunction. In this study, we investigated the possible involvement of the mitochondrial genomic variants in 101 patients and 71 controls by direct sequencing of the entire mitochondrial genome. The number of variable positions in the mtDNA with respect to the revised Cambridge Reference Sequence (rCRS), have been designated "Segregating Sites". The segregating sites present only in the patients or controls have been designated "Unique Segregating Sites (USS)". The population mutation rate (θ = 4Neμ) as estimated by Watterson's θ (θw), considering only the USS, was significantly higher among the patients (p = 9.8 × 10(-15)) compared to controls. The difference in θw and the number of USS were more pronounced when restricted to the coding region (p<1.31 × 10(-21) and p = 0.006607, respectively). Further analysis of the region revealed non-synonymous variations were significantly higher in Complex I among the patients (p = 0.0053). Similar trends were retained when USS was considered only within complex I (frequency 0.49 vs 0.31 with p<0.0001 and mutation rate p-value <1.49×10(-43)) and ND5 within its gene cluster (frequency 0.47 vs 0.23 with p<0.0001 and mutation rate p-value <4.42×10(-47)). ND5 is involved in the proton pumping mechanism. Incidentally, glaucomatous trabecular meshwork cells have been reported to be more sensitive to inhibition of complex I activity. Thus mutations in ND5, expected to inhibit complex I activity, could lead to generation of oxidative stress and favor glaucomatous condition.
format	article
author	Deblina Banerjee Antara Banerjee Suddhasil Mookherjee Mansi Vishal Arijit Mukhopadhyay Abhijit Sen Analabha Basu Kunal Ray
author_facet	Deblina Banerjee Antara Banerjee Suddhasil Mookherjee Mansi Vishal Arijit Mukhopadhyay Abhijit Sen Analabha Basu Kunal Ray
author_sort	Deblina Banerjee
title	Mitochondrial genome analysis of primary open angle glaucoma patients.
title_short	Mitochondrial genome analysis of primary open angle glaucoma patients.
title_full	Mitochondrial genome analysis of primary open angle glaucoma patients.
title_fullStr	Mitochondrial genome analysis of primary open angle glaucoma patients.
title_full_unstemmed	Mitochondrial genome analysis of primary open angle glaucoma patients.
title_sort	mitochondrial genome analysis of primary open angle glaucoma patients.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/fa1ee968be30473ebf15d4a30dd73bb6
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Mitochondrial genome analysis of primary open angle glaucoma patients.

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