Journal of Genetics

, Volume 95, Issue 2, pp 459–461 | Cite as

TBK1 duplication is found in normal tension and not in high tension glaucoma patients of Indian origin

  • KUNAL RAYEmail author


Duplication in TANK-binding kinase 1 (TBK1) gene has been shown to be associated with normal tension glaucoma (NTG), a subtype of the neurodegenerative disease glaucoma, which is the largest cause of irreversible blindness. A specific Taqman assay was used in exploring the genetic contribution of the duplication in TBK1 on 158 NTG and 161 high tension glaucoma (HTG) patients as well as in 197 controls from West Bengal, eastern part of India. We identified two patients in NTG subgroup harbouring the duplication (1.26%). Both the patients harboured one extra copy for the genomic segment analysed. No copy number change was observed in the HTG subgroup or in the controls. This is the first report showing presence of duplication in TBK1 in Indian primary open angle glaucoma (POAG) cohort, especially for the NTG subtype. Our finding correlates with the previous findings where duplication in TBK1 is shown to be associated with NTG in various populations.

Glaucoma is a...


TBK1 gene copy number variation primary open angle glaucoma normal tension glaucoma. 



We acknowledge Dr John Fingert for providing us the DNA sample to be used as positive control to standardize the assay for the duplication. Funding from the Council of Scientific and Industrial Research (CSIR) supported the work (grant numbers BSC-0123 and MLP-0016). LK and MV acknowledge CSIR and Indian Council of Medical Research (ICMR) for their senior research fellowships.

Supplementary material

12041_2016_637_MOESM1_ESM.pdf (541 kb)
(PDF 541 KB)


  1. Awadalla M. S., Fingert J. H., Roos B. E., Chen S., Holmes R., Graham S. L. et al. 2014 Copy number variations of TBK1 in Australian patients with primary open angle glaucoma. Am. J. Ophthalmol. 159, 124–130.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Fingert J. H., Robin A. L., Stone J. L., Roos B. R., Davis L. K., Scheetz T. E. et al. 2011 Copy number variations on chromosome 12q14 in patients with normal tension glaucoma. Hum. Mol. Genet. 20, 2482–2494.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Freischmidt A., Wieland T., Richter B., Ruf W., Schaeffer V., Muller K. et al. 2015 Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat. Neurosci. 5, 631–636.CrossRefGoogle Scholar
  4. Janssen S. F., Gorgels T. G., Ramdas W. D., Klaver C. C., van Duijn C. M., Jansonius N. M. et al. 2013 The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog. Retin. Eye Res. 37, 31–67.CrossRefPubMedGoogle Scholar
  5. Kaurani L., Vishal M., Kumar D., Sharma A., Mehani B., Sharma C. et al. 2014 Gene rich large deletions are overrepresented in POAG patients of Indian and Caucasian origins. Invest. Ophthalmol. Vis. Sci. 24, 3258–3264.CrossRefGoogle Scholar
  6. Kawase K., Allingham R. R., Meguro A., Mizuki N., Roos B., Solivan-Timpe F. M. et al. 2012 Confirmation of TBK1 duplication in normal tension glaucoma. Exp. Eye Res. 96, 178–180.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Livak K. J. and Schmittgen T. D. 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402–408.CrossRefPubMedGoogle Scholar
  8. Minegishi Y., Iejima D., Kobayashi H., Chi Z. L., Kawase K., Yamamoto T. et al. 2013 Enhanced optineurin E50K-TBK1 interaction evokes protein insolubility and initiates familial primary open-angle glaucoma. Hum. Mol. Genet. 22, 3559–3567.CrossRefPubMedGoogle Scholar
  9. Morton S., Hesson L., Peggie M. and Cohen P. 2008 Enhanced binding of TBK1 by an optineurin mutant that causes a familial form of primary open angle glaucoma. FEBS Lett. 582, 997–1002.CrossRefPubMedGoogle Scholar
  10. Nikolskaya T., Nikolsky Y., Serebryiskaya T., Zvereva S., Sviridov E., Dezso Z. et al. 2009 Network analysis of human glaucomatous optic nerve head astrocytes. BMC Med. Genomics 2, 24.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Quigley H. A. and Broman A. T. 2006 The number of people with glaucoma worldwide in 2010 and 2020. Br. J. Ophthalmol. 90, 262–267.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Ritch R., Darbro B., Menon G., Khanna C. L., Solivan-Timpe F., Roos B. R. et al. 2014 TBK1 Gene duplication and normal-tension glaucoma. JAMA Ophthalmol. 132, 544–548.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Trocoli A. and Djavaheri-Mergny M. 2011 The complex interplay between autophagy and NF-kappaB signaling pathways in cancer cells. Am. J. Cancer Res. 1, 629–649.PubMedPubMedCentralGoogle Scholar

Copyright information

© Indian Academy of Sciences 2016

Authors and Affiliations

  1. 1.Genomics and Molecular MedicineCSIR-Institute of Genomics and Integrative BiologyNew DelhiIndia
  2. 2.Molecular and Human Genetics DivisionCSIR-Indian Institute of Chemical BiologyKolkataIndia
  3. 3.Sachindra Nath Pradhan Centre for NeurosciencesUniversity of CalcuttaKolkataIndia
  4. 4.Dristi PradipKolkataIndia
  5. 5.Academy of Scientific and Innovative Research (AcSIR)New DelhiIndia

Personalised recommendations