• NORFATIMAH MOHAMED YUNUS Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia
  • UMI NABILA MAT YUSUF Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia
  • LYENA WATTY ZURAINE AHMAD Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia
  • ROZIAH KAMBOL Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia
  • NURUL AILI ZAKARIA Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia


Animal model, epilepsy, epilepsy genes, Japanese medaka, zebrafish


Epilepsy is a chronic neurological disorder that has affected around 50-70 million people worldwide. Various animal models have previously been used in epilepsy research. To expand the knowledge of the disease, a new animal model is suggested to be explored considering the genetic and phenotypic heterogeneity that contributes to the complexity of the disease. This study was undertaken to analyze 14 causative genes of epilepsy disease in Japanese medaka (Oryzias latipes), humans, and the established model of this disease which is zebrafish (Danio rerio) by assessing the variation in the genes by using MEGA X and predicting the functional motif and secondary structure of the proteins by using PROSITE and GORIV respectively. Results from the variation analysis showed the lowest percentage of conserved genes in Japanese medaka was 60%.50% of the genes of Japanese medaka were found to be more conserved than zebrafish in comparison to a human. The functional motifs present in all genes in Japanese medaka showed the same motifs present in humans. All the secondary structures of Japanese medaka genes were predicted to contain the alpha helix, extended strand, and random coil. In conclusion, it can be inferred that Japanese medaka could be a reliable animal model for epilepsy disease.


Download data is not yet available.


Metrics Loading ...


Bateman, A., Martin, M.-J., Orchard, S., Magrane, M., Agivetova, R., Ahmad, S., Alpi, E., Bowler-Barnett, E. H., Britto, R., Bursteinas, B., Bye-A-Jee, H., Coetzee, R., Cukura, A., Da Silva, A., Denny, P., Dogan, T., Ebenezer, T., Fan, J., Castro, L. Garmiri, P., Georghiou, G., Gonzales, L., Hatton-Ellis, E., Hussein, A., Ignatchenko, A., Insana, G., Ishtiaq, R., Jokinen, P., Joshi, V., Jyothi, D., Lock, A., Lopez, R., Luciani, A., Luo, J., Lussi, Y., MacDougall, A., Madeira, F., Mahmoudy, M., Menchi, M., Mishra, A., Moulang, K., Nightingale, A., Oliveira, C., Pundir, S., Qi, G., Raj, S., Rice, D., Lopez, M., Saidi, R., Sampson, J., Sawford, T., Speretta, E., Turner, E., Tyagi, N., Vasudev, P., Volynkin, V., Warner, K., Watkins, X., Zaru, R., Zellner, H., Bridge, A., Poux, S., Redaschi, N., Aimo, L., Argoud-Puy, G., Auchincloss, A., Axelsen, K., Bansal, P., Baratin, D., Blatter, M., Bolleman, J., Boutet, E., Breuza, L., Casals-Casas, C., de Castro, E., Echioukh, K., Coudert, E., Cuche, B., Doche, M., Dornevil, D., Estreicher, A., Famiglietti, M., Feuermann, M., Gasteiger, E., Gehant, S., Gerritsen, V., Gos, A., Gruaz-Gumowski, N., Hinz, U., Hulo, C., Hyka-Nouspikel, N., Jungo, F., Keller, G., Kerhornou, A., Lara, V., Le Mercier, P., Lieberherr, D., Lombardot, T., Martin, X., Masson, P., Morgat, A., Neto, T., Paesano, S., Pedruzzi, I., Pilbout, S., Pourcel, L., Pozzato, M., Pruess, M., Rivoire, C., Sigrist, C., Sonesson, K., Stutz, A., Sundaram, S., Tognolli, M., Verbregue, L., Wu, C., Arighi, C., Arminski, L., Chen, C., Chen, Y., Garavelli, J., Huang, H., Laiho, K., McGarvey, P., Natale, D., Ross, K., Vinayaka, C., Wang, Q., Wang, Y., Yeh, L., Zhang, J., Ruch, P. &Teodoro, D. 2021. UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Research, 49(D1): D480–D489. DOI: https://doi.org/10.1093/nar/gkaa1100

Cho, S. J., Park, E., Baker, A. & Reid, A.Y. 2020. Age bias in zebrafish models of epilepsy : What can we learn from old fish? Frontiers in Cell and Developmental Biology, 8(573303): 1–8. DOI: https://doi.org/10.3389/fcell.2020.573303

Coughlin, C. R., Swanson, M. A., Spector, E., Meeks, N. J. L., Kronquist, K. E., Aslamy, M., Wempe, M.F., van Karnebeek, C.D.M., Gospe, S.M., Aziz, V.G., Tsai, B.P., Gao, H., Nagy, P.L., Hyland, K., van Dooren, S.J.M., Salomons, G.S. & Van Hove, J.L.K. 2019. The genotypic spectrum of ALDH7A1 mutations resulting in pyridoxine dependent epilepsy: A common epileptic encephalopathy. Journal of Inherited Metabolic Disease, 42(2): 353–361. DOI: https://doi.org/10.1002/jimd.12045

Cunliffe, V.T., Baines, R.A., Giachello, C.N.G., Lin, W.H., Morgan, A., Reuber, M., Russell, C., Walker, M.C. & Williams, R.S.B. 2015. Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms. Seizure, 24: 44–51. DOI: https://doi.org/10.1016/j.seizure.2014.09.018

de Castro, E., Sigrist, C.J.A., Gattiker, A., Bulliard, V., Langendijk-Genevaux, P.S., Gasteiger, E., Bairoch, A. & Hulo, N. 2006. ScanProsite: Detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins. Nucleic Acids Research, 34(WEB. SERV. ISS.): W362-5. DOI: https://doi.org/10.1093/nar/gkl124

Decui, L., Luisa, C., Garbinato, L., Ester, S., Cristina, S., Rodrigues, E., Pablo, G., Aguiar, S., Girardi, L., Oliveira, J.V., Maria, A., Garbinato, C. L. L., Schneider, S. E., Mazon, S. C., Almeida, E.R., Aguiar, G.P.S., Muller, L.G., Oliveira, J.V. & Siebel, A.M. 2020. Micronized resveratrol shows promising effects in a seizure model in zebrafish and signalizes an important advance in epilepsy treatment. Epilepsy Research, 159: 1–6. DOI: https://doi.org/10.1016/j.eplepsyres.2019.106243

Degrève, L., Fuzo, C.A. & Caliri, A. 2014. Extended secondary structures in proteins. Biochimica et Biophysica Acta - Proteins and Proteomics, 1844(2): 384–388. DOI: https://doi.org/10.1016/j.bbapap.2013.10.005

Ellis, C.A., Petrovski, S. & Berkovic, S.F. 2020. Epilepsy genetics: Clinical impacts and biological insights. The Lancet Neurology, 19(1): 93–100. DOI: https://doi.org/10.1016/S1474-4422(19)30269-8

Fogle, K.J., Smith, A.R., Satterfield, S.L., Gutierrez, A.C., Hertzler, J.I., McCardell, C.S., Shon, J.H., Barile, Z.J., Novak, M.O. & Palladino, M.J. 2019. Ketogenic and anaplerotic dietary modifications ameliorate seizure activity in Drosophila models of mitochondrial encephalomyopathy and glycolytic enzymopathy. Molecular Genetics and Metabolism, 126: 439–447. DOI: https://doi.org/10.1016/j.ymgme.2019.01.008

French, J.A. & Staley, B.A. 2012. AED treatment through different ages: As our brains change, should our drug choices also? Epilepsy Currents, 12(3): 22–27. DOI: https://doi.org/10.5698/1535-7511-12.4s.22

Garnier, J., Gibrat, J.F. & Robson, B. 1996. GOR method for predicting protein secondary structure from amino acid sequence. Methods in Enzymology, 266: 540–553. DOI: https://doi.org/10.1016/S0076-6879(96)66034-0

George, A.J., Hoffiz, Y.C., Charles, A.J., Zhu, Y. & Mabb, A.M. 2018. A comprehensive atlas of E3 ubiquitin ligase mutations in neurological disorders. Frontiers in Genetics, 9: 29. DOI: https://doi.org/10.3389/fgene.2018.00029

Grone, B.P. & Baraban, S.C. 2015. Animal models in epilepsy research : Legacies and new directions. Nature Neuroscience, 18(3): 339–343. DOI: https://doi.org/10.1038/nn.3934

Haimov, B. & Srebnik, S. 2016. A closer look into the alpha-helix basin. Scientific Reports, 6(1): 38341. DOI: https://doi.org/10.1038/srep38341

Hewapathirane, D.S., Dunfield, D., Yen, W., Chen, S., Haas, K., Dun, D., Yen, W., Chen, S., Haas, K., Dunfield, D., Yen, W., Chen, S. & Haas, K. 2008. In vivo imaging of seizure activity in a novel developmental seizure model. Experimental Neurology, 211(2): 480–488. DOI: https://doi.org/10.1016/j.expneurol.2008.02.012

Ikpeme, E.V., Udensi, O.U., Kooffreh, M.E., Etta, H.E., Ushie, B.B., Echea, E. & Ozoje, M. 2016. In silico analysis of BRCA1 gene and its phylogenetic relationship in some selected domestic animal species. Trends in Bioinformatics, 10(1): 1–10. DOI: https://doi.org/10.3923/tb.2017.1.10

Isenbarger, T.A., Carr, C.E., Johnson, S.S., Finney, M., Church, G.M., Gilbert, W., Zuber, M.T. & Ruvkun, G. 2008. The most conserved genome segments for life detection on Earth and other planets. Origins of Life and Evolution of Biospheres, 38(6): 517–533. DOI: https://doi.org/10.1007/s11084-008-9148-z

Johan Arief, M.F., Choo, B.K.M., Yap, J.L., Kumari, Y. & Shaikh, M.F. 2018. A systematic review on non-mammalian models in epilepsy research. Frontiers in Pharmacology, 9(655): 1–23. DOI: https://doi.org/10.3389/fphar.2018.00655

Katsumura, T., Oda, S., Mitani, H. & Oota, H. 2019. Medaka population genome structure and demographic history described via genotyping-by-sequencing. Genes, Genomes, Genetics, 9: 217–228. DOI: https://doi.org/10.1534/g3.118.200779

Kristan Jr., W.B., Calabrese, R.L., Friesen, W. O., Kristan, W.B., Calabrese, R.L., Friesen, W.O., Kristan Jr., W.B., Calabrese, R.L. & Friesen, W.O. 2005. Neuronal control of leech behavior. Progress in Neurobiology, 76(5): 279–327. DOI: https://doi.org/10.1016/j.pneurobio.2005.09.004

Kumar, S., Nei, M., Dudley, J. & Tamura, K. 2008. MEGA: A biologist-centric software for evolutionary analysis of DNA and protein sequences. Brief Bioinformatics, 9(4): 299–306. DOI: https://doi.org/10.1093/bib/bbn017

Kwon, C.S., Ripa, V., Al-Awar, O., Panov, F., Ghatan, S., Jetté, N. & Jette, N. 2018. Epilepsy and neuromodulation-randomized controlled trials. Brain Sciences, 8(4): 1–22. DOI: https://doi.org/10.3390/brainsci8040069

Locke, C.J., Williams, S.N., Schwarz, E. M., Caldwell, G.A. & Caldwell, K.A. 2006. Genetic interactions among cortical malformation genes that influence susceptibility to convulsions in C. elegans. Brain Research, 1120(1): 23–34. DOI: https://doi.org/10.1016/j.brainres.2006.08.067

Ma, Y., Liu, Y. & Cheng, J. 2018. Protein secondary structure prediction based on data partition and semi-random subspace method. Scientific Reports, 8(1): 9856. DOI: https://doi.org/10.1038/s41598-018-28084-8

Matsumoto, Y., Oota, H., Asaoka, Y., Nishina, H., Watanabe, K., Bujnicki, J.M., Oda, S., Kawamura, S. & Mitani, H. 2009. Medaka: A promising model animal for comparative population genomics. BMC Research Notes, 2(1): 88. DOI: https://doi.org/10.1186/1756-0500-2-88

McTague, A., Howell, K.B., Cross, J.H., Kurian, M.A. & Scheffer, I.E. 2016. The genetic landscape of the epileptic encephalopathies of infancy and childhood. The Lancet Neurology, 15(3): 304–316. DOI: https://doi.org/10.1016/S1474-4422(15)00250-1

Mulley, J.C., Scheffer, I.E., Petrou, S. & Berkovic, S.F. 2003. Channelopathies as a genetic cause of epilepsy. Current Opinion in Neurology, 16(2): 171–176. DOI: https://doi.org/10.1097/00019052-200304000-00009

Naruse, K., Chisada, S., Sasado, T. & Takehana, Y. 2016. Medaka as model animal and current status of medaka biological resources. Research & Knowledge, 2(1): 31–34.

Scheffer, I.E., Berkovic, S., Capovilla, G., Connolly, M.B., French, J., Guilhoto, L., Hirsch, E., Jain, S., Mathern, G.W., Moshé, S.L., Nordli, D.R., Perucca, E., Tomson, T., Wiebe, S., Zhang, Y. & Zuberi, S.M. 2017. ILAE classification ofthe epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 58(4): 512–521. DOI: https://doi.org/10.1111/epi.13709

Shortall, K., Djeghader, A., Magner, E. & Soulimane, T. 2021. Insights into aldehyde dehydrogenase enzymes: A structural perspective. Frontiers in Molecular Biosciences, 8: 659550. DOI: https://doi.org/10.3389/fmolb.2021.659550

Smith, L.J., Fiebig, K.M., Schwalbe, H. & Dobson, C.M. 1996. The concept of a random coil: Residual structure in peptides and denatured proteins. Folding and Design, 1(5): R95–R106. DOI: https://doi.org/10.1016/S1359-0278(96)00046-6

Tanner, R. 2018. The 3Rs: What are medical scientists doing about animal testing? Frontiers for Young Minds, 6(44): 1–8. DOI: https://doi.org/10.3389/frym.2018.00044

van der Staay, F.J., Arndt, S.S. & Nordquist, R.E. 2009. Evaluation of animal models of neurobehavioral disorders. Behavioral and Brain Functions, 5(1): 11. DOI: https://doi.org/10.1186/1744-9081-5-11

Wang, J., Lin, Z.-J., Liu, L., Xu, H.-Q., Shi, Y.-W., Yi, Y.-H., He, N. & Liao, W.-P. 2017. Epilepsy-associated genes. Seizure, 44: 11–20. DOI: https://doi.org/10.1016/j.seizure.2016.11.030

Weimbs, T., Low, S.H., Chapin, S.J., Mostov, K.E., Bucher, P. & Hofmann, K. 1997. A conserved domain is present in different families of vesicular fusion proteins: A new superfamily. Proceedings of the National Academy of Sciences, 94(7): 3046–3051. DOI: https://doi.org/10.1073/pnas.94.7.3046

West, S., Nevitt, S.J., Cotton, J., Gandhi, S., Weston, J., Sudan, A., Ramirez, R. & Newton, R. 2019. Surgery for epilepsy. Cochrane Database of Systematic Reviews, 6. DOI: https://doi.org/10.1002/14651858.CD010541.pub3

Wolking, S., May, P., Mei, D., Møller, R.S., Balestrini, S., Helbig, K.L., Altuzarra, C.D., Chatron, N., Kaiwar, C., Stöhr, K., Widdess-Walsh, P., Mendelsohn, B.A., Numis, A., Cilio, M.R., Van Paesschen, W., Svendsen, L.L., Oates, S., Hughes, E., Goyal, S., Brown, K., Sifuentes Saenz, M., Dorn, T., Muhle, H., Pagnamenta, A., Vavoulis, D., Knight, S., Taylor, J., Canevini, M., Darra, F., Gavrilova, R., Powis, Z., Tang, S., Marquetand, J., Armstrong, M., McHale, D., Klee, E., Kluger, G., Lowenstein, D., Weckhuysen, S., Pal, D., Helbig, I., Guerrini, R., Thomas, R., Rees, M., Lesca, G., Sisodiya, S., Weber, Y., Lal, D., Marini, C., Lerche, H., Schubert, J. 2019. Clinical spectrum of STX1B-related epileptic disorders. Neurology, 92(11): e1238–e1249. DOI: https://doi.org/10.1212/WNL.0000000000007089

World Health Organization. 2019. Epilepsy. WHO. URL https://www.who.int/news-room/fact-sheets/detail/epilepsy (accessed 11.8.20).



How to Cite

MOHAMED YUNUS, N., MAT YUSUF, U. N. ., AHMAD, L. W. Z. ., KAMBOL, R. ., ARIS, F. ., & ZAKARIA, N. A. . . (2022). Oryzias latipes (JAPANESE MEDAKA) AS GENETIC MODEL TO STUDY CAUSATIVE GENES OF EPILEPSY DISEASE: AN IN-SILICO APPROACH. Malaysian Applied Biology, 51(4), 75–86. https://doi.org/10.55230/mabjournal.v51i4.14

Most read articles by the same author(s)