title: Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants.
abstract: OBJECTIVE
  The aim of this study was to determine whether mutations in mitochondrial DNA play a role in high-pressure primary open-angle glaucoma (OMIM 137760) by analyzing new data from massively parallel sequencing of mitochondrial DNA.
  
  
  METHODS
  Glaucoma patients with high-tension primary open-angle glaucoma and ethnically matched and age-matched control subjects without glaucoma were recruited. The entire human mitochondrial genome was amplified in two overlapping fragments by long-range polymerase chain reaction and used as a template for massively parallel sequencing on an Ion Torrent Personal Genome Machine. All variants were confirmed by conventional Sanger sequencing.
  
  
  RESULTS
  Whole-mitochondrial genome sequencing was performed in 32 patients with primary open-angle glaucoma from India (n = 16) and Ireland (n = 16). In 16 of the 32 patients with primary open-angle glaucoma (50% of cases), there were 22 mitochondrial DNA mutations consisting of 7 novel mutations and 8 previously reported disease-associated sequence variants. Eight of 22 (36.4%) of the mitochondrial DNA mutations were in complex I mitochondrial genes.
  
  
  CONCLUSIONS
  Massively parallel sequencing using the Ion Torrent Personal Genome Machine with confirmation by Sanger sequencing detected a pathogenic mitochondrial DNA mutation in 50% of the primary open-angle glaucoma cohort. Our findings support the emerging concept that mitochondrial dysfunction results in the development of glaucoma and, more specifically, that complex I defects play a significant role in primary open-angle glaucoma pathogenesis.
authors.affiliation: Department of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Madurai, India.
authors.forename: Periasamy
authors.identifier: 0000000205998653
authors.initials: P
authors.lastname: Sundaresan
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Simpson
authors.affiliation: 1] Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK [2] Poona Blind Men's Association's (PBMA's) H. V. Desai Eye Hospital, Pune, India.
authors.forename: Chitra
authors.initials: C
authors.lastname: Sambare
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, UK.
authors.forename: Seamus
authors.initials: S
authors.lastname: Duffy
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Lechner
authors.affiliation: Department of Genetics, Deenanth Mangeshkar Hospital, Pune, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Dastane
authors.affiliation: Institute of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Dervan
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
authors.forename: Neeru
authors.initials: N
authors.lastname: Vallabh
authors.affiliation: Poona Blind Men's Association's (PBMA's) H. V. Desai Eye Hospital, Pune, India.
authors.forename: Vidya
authors.initials: V
authors.lastname: Chelerkar
authors.affiliation: Poona Blind Men's Association's (PBMA's) H. V. Desai Eye Hospital, Pune, India.
authors.forename: Madan
authors.initials: M
authors.lastname: Deshpande
authors.affiliation: Institute of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Colm
authors.initials: C
authors.lastname: O'Brien
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, UK.
authors.forename: Amy Jayne
authors.initials: AJ
authors.lastname: McKnight
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
authors.forename: Colin E
authors.initials: CE
authors.lastname: Willoughby
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D015894:Genome, Human; D054629:Genome, Mitochondrial; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007194:India; D009154:Mutation; D010375:Pedigree
chemical_list: D004272:DNA, Mitochondrial; D005136:Eye Proteins