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Mitochondrial DNA changes in glaucoma patients

Mitochondrial DNA nucleotide changes in primary congenital glaucoma patients.

Genetic analysis showed that glaucoma patients belong to three groups. Fifty percent of the patients belonged to one group (the H2a2a lineage of the N-derived haplogroup*).

*In human genetics, a human mitochondrial DNA haplogroup is, roughly, a group genes that a progeny inherits from the mother that share a common ancestor having the same single nucleotide polymorphism (SNP) mutation.

Haplogroups are used to represent the major branch points on the mitochondrial phylogenetic tree. Understanding the evolutionary path of the female lineage has helped population geneticists trace the matrilineal inheritance of modern humans back to human origins in Africa and the subsequent spread around the globe.

The letter names of the haplogroups (not just mitochondrial DNA haplogroups) run from A to Z. As haplogroups were named in the order of their discovery, they (meaning the accidental dictionary ordering of the letters) do not reflect the actual genetic relationships. ~ Wikipedia


Primary congenital glaucoma (PCG) is the second most common cause of blindness, accounting for 0.01%-0.04% of total blindness worldwide. Most congenital glaucoma cases are mapped to the GLC3A locus, and many aspects of PCG are still unknown. Recent studies have reported an increased frequency of mitochondrial DNA (mtDNA) sequence changes in primary open-angle glaucoma, primary angle-closure glaucoma, and pseudoexfoliation glaucoma compared to controls. Thus, this study was planned with the aim of detecting mitochondrial DNA variations in PCG cases.


Twenty primary congenital glaucoma cases were selected from Dr. R. P. Centre for Ophthalmic Sciences of All India Institute of Medical Sciences (AIIMS), New Delhi, India. DNA was isolated from whole blood samples. The entire coding region of the mitochondrial genome was amplified by PCR in 20 patients and 20 controls. The full mtDNA genome was sequenced and analyzed against mitochondrial reference sequence NC_012920.


MtDNA sequencing revealed a total of 195 nucleotide variations in PCG patients and 58 in controls. Of the 195 changes, 43 (22.05%) were nonsynonymous, 82 (42.05%) were synonymous, and 30 were in RNA genes. A total of 39/195 (20.00%) variations were observed in the D-loop (hypervariable region), 19/195 (9.74%) in different ribosomal RNA (rRNAs), 11/195 (5.64%) in transfer RNA (tRNAs), 66/195 (33.84%) in complex I, 17/195 (8.71%) in complex III, 27/195 (13.84%) in complex IV, and 15/195 (7.69%) in complex V. Of 58 variations in the controls, 14 were nonsynonymous changes. The Sorting Intolerant from Tolerant and Polymorphism Phenotyping analyses of all nonsynonymous changes from patients revealed two pathogenic changes in NADH-ubiquinone oxidoreductase chain 2 (ND2) and cytochrome oxidase subunit III (COXIII) subunits. In one of the patients, the insertion of cytosine introduced a frame shift change (p.Ile104AsnfsX26) in the cytochrome b (CYB) subunit of the electron transport chain. In another patient, a variation (G8572A) in ATP synthase 8 (ATpase8) led to the introduction of a stop codon or termination at amino acid position 69.

Haplogroup/phylogenetic analysis of mtDNA showed that primary congenital glaucoma patients belong to three macrohaplogroups: M (4), N (15), and L (1). Fifty percent of the patients belonged to the H2a2a lineage of the N-derived haplogroup.


Although several mutations were found at a higher frequency among our population, there is a need to complement this study with functional studies and to analyze a large number of samples in different populations of different haplogroups, as penetrance varies among haplogroups.

Free PMC Full Text Article

Mol Vis. 2013;19:220-30. Epub 2013 Feb 1.
Mitochondrial DNA nucleotide changes in primary congenital glaucoma patients.
Kumar M1, Tanwar M, Faiq MA, Pani J, Shamsi MB, Dada T, Dada R.

    [PubMed - indexed for MEDLINE]

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