Differential Expression Analysis on Schizophrenia Dataset Suggests Pseudogene RNU6-505P as under Selective Pressure

Emilio Mastriani; Alexey V Rakov; Shu-Lin Liu

doi:10.21467/ias.9.1.86-99

Authors

Emilio Mastriani Harbin Medical University
Alexey V Rakov Laboratory of Molecular Epidemiology and Ecology of Pathogenic Bacteria, Somov Institute of Epidemiology and Microbiology, Vladivostok, Russia
Shu-Lin Liu Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada

DOI:

https://doi.org/10.21467/ias.9.1.86-99

Abstract

Schizophrenia is one of the 15 leading causes of disability worldwide. About 1% of the global population has schizophrenia, with 10% of premature mortality chance. Schizophrenia is therefore associated with significant health, social and economic concerns. In this context, thalamus and striatum areas play important roles as much in schizophrenia as processing information before reaching the conscious thought: step happening soon in the creativity action. Creativity is defined by psychological scientists as the generation of ideas or products that are both original and valuable. Creativity relies on imagination and this fundamental human ability remains understudied in comparison to other important psychological phenomena. It is natural to ask whether the gene expression profiling of samples from schizophrenic patients could highlight the activity of some genes specific to humans. Microarray analysis of the dataset GSE25673 revealed that the pseudogene RNU6-505P is expressed differentially in schizophrenic samples and correlates to CYP26A1, ARHGAP18, TSPAN12, HEY2 and TMEM132A genes. Ontological analysis showed that the RNU6-505P pseudogene is involved in brain development and certain neurological pathologies. Evolutionary analysis showed that the AGA 3-nucleotide sequence of RNU6-505P has been under positive selective pressure. Finally, the 1-nucleotide mutation prediction test revealed that variations on the AGA nucleotides could be fatal to the RNA structure of the sequence. We conclude that differential expression of the RNU6-505P pseudogene can be valid to diagnose schizophrenia and the RNU6-505P pseudogene may have a relevant function in the cerebral development and in the divergent evolution of humans from apes.

Keywords:

Differential expression, Brain, Evolution, Microarray, Schizophrenia, Pseudo-gene, RNU6-505P, Secondary structure prediction

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References

O. de Manzano, S. Cervenka, A. Karabanov, L. Farde, and F. Ullen, "Thinking outside a less intact box: thalamic dopamine D2 receptor densities are negatively related to psychometric creativity in healthy individuals," PLoS One, vol. 5, no. 5, p. e10670, May 17 2010.

I. R. Reddy, J. Ukrani, V. Indla, and V. Ukrani, "Creativity and psychopathology: Two sides of the same coin?," Indian J Psychiatry, vol. 60, no. 2, pp. 168-174, Apr-Jun 2018.

J. Parnas, K. E. Sandsten, C. H. Vestergaard, and J. Nordgaard, "Schizophrenia and Bipolar Illness in the Relatives of University Scientists: An Epidemiological Report on the Creativity-Psychopathology Relationship," Front Psychiatry, vol. 10, p. 175, 2019.

C. Asanuma, W. T. Thach, and E. G. Jones, "Cytoarchitectonic delineation of the ventral lateral thalamic region in the monkey," Brain Res, vol. 286, no. 3, pp. 219-35, May 1983.

S. Sabunciyan, "Gene Expression Profiles Associated with Brain Aging are Altered in Schizophrenia," Sci Rep, vol. 9, no. 1, p. 5896, Apr 11 2019.

M. Li et al., "A powerful conditional gene-based association approach implicated functionally important genes for schizophrenia," Bioinformatics, vol. 35, no. 4, pp. 628-635, Feb 15 2019.

M. Manchia et al., "Pattern of gene expression in different stages of schizophrenia: Down-regulation of NPTX2 gene revealed by a meta-analysis of microarray datasets," Eur Neuropsychopharmacol, vol. 27, no. 10, pp. 1054-1063, Oct 2017.

O. Bergman, R. Karry, J. Milhem, and D. Ben-Shachar, "NDUFV2 pseudogene (NDUFV2P1) contributes to mitochondrial complex I deficits in schizophrenia," Mol Psychiatry, Dec 10 2018.

K. J. Brennand et al., "Modelling schizophrenia using human induced pluripotent stem cells," Nature, vol. 473, no. 7346, pp. 221-5, 2011.

B. S. Carvalho and R. A. Irizarry, "A framework for oligonucleotide microarray preprocessing," Bioinformatics, vol. 26, no. 19, pp. 2363-7, Oct 1 2010.

R. C. Gentleman et al., "Bioconductor: open software development for computational biology and bioinformatics," Genome Biol, vol. 5, no. 10, p. R80, 2004.

M. E. Ritchie et al., "limma powers differential expression analyses for RNA-sequencing and microarray studies," Nucleic Acids Res, vol. 43, no. 7, p. e47, Apr 20 2015.

L. Scrucca, M. Fop, T. B. Murphy, and A. E. Raftery, "mclust 5: Clustering, Classification and Density Estimation Using Gaussian Finite Mixture Models," R J, vol. 8, no. 1, pp. 289-317, Aug 2016.

U. K. Muppirala, V. G. Honavar, and D. Dobbs, "Predicting RNA-protein interactions using only sequence information," BMC Bioinformatics, vol. 12, p. 489, Dec 22 2011.

B. A. Lewis et al., "PRIDB: a Protein-RNA interface database," Nucleic Acids Res, vol. 39, no. Database issue, pp. D277-82, Jan 2011.

S. F. Altschul, W. Gish, W. Miller, E. W. Myers, and D. J. Lipman, "Basic local alignment search tool," J Mol Biol, vol. 215, no. 3, pp. 403-10, Oct 5 1990.

G. Feng, P. Shaw, S. T. Rosen, S. M. Lin, and W. A. Kibbe, "Using the bioconductor GeneAnswers package to interpret gene lists," Methods Mol Biol, vol. 802, pp. 101-12, 2012.

J. Paquette and T. Tokuyasu, "EGAN: exploratory gene association networks," Bioinformatics, vol. 26, no. 2, pp. 285-6, Jan 15 2010.

D. Maglott, J. Ostell, K. D. Pruitt, and T. Tatusova, "Entrez Gene: gene-centered information at NCBI," Nucleic Acids Res, vol. 39, no. Database issue, pp. D52-7, Jan 2011.

J. S. Amberger, C. A. Bocchini, F. Schiettecatte, A. F. Scott, and A. Hamosh, "OMIM.org: Online Mendelian Inheritance in Man (OMIM(R)), an online catalog of human genes and genetic disorders," Nucleic Acids Res, vol. 43, no. Database issue, pp. D789-98, Jan 2015.

S. Lindsay and A. J. Copp, "MRC-Wellcome Trust Human Developmental Biology Resource: enabling studies of human developmental gene expression," Trends Genet, vol. 21, no. 11, pp. 586-90, Nov 2005.

J. Huerta-Cepas, F. Serra, and P. Bork, "ETE 3: Reconstruction, Analysis, and Visualization of Phylogenomic Data," Mol Biol Evol, vol. 33, no. 6, pp. 1635-8, Jun 2016.

Z. Yang, "PAML 4: phylogenetic analysis by maximum likelihood," Mol Biol Evol, vol. 24, no. 8, pp. 1586-91, Aug 2007.

J. P. Bielawski and Z. Yang, "A maximum likelihood method for detecting functional divergence at individual codon sites, with application to gene family evolution," J Mol Evol, vol. 59, no. 1, pp. 121-32, Jul 2004.

Z. Yang and R. Nielsen, "Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages," Mol Biol Evol, vol. 19, no. 6, pp. 908-17, Jun 2002.

J. Zhang, R. Nielsen, and Z. Yang, "Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level," Mol Biol Evol, vol. 22, no. 12, pp. 2472-9, Dec 2005.

R. B. Denman, "Using RNAFOLD to predict the activity of small catalytic RNAs," Biotechniques, vol. 15, no. 6, pp. 1090-5, Dec 1993.

G. Stelzer et al., "The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses," Curr Protoc Bioinformatics, vol. 54, pp. 1 30 1-1 30 33, Jun 20 2016.

Q. Wang et al., "A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data," Nat Neurosci, vol. 22, no. 5, pp. 691-699, May 2019.

Q. Xie, W. Shen, Z. Li, A. Baranova, H. Cao, and Z. Li, "A core collection of pan-schizophrenia genes allows building cohort-specific signatures of affected brain," Sci Rep, vol. 9, no. 1, p. 12671, Sep 3 2019.

N. E. Clifton et al., "Dynamic expression of genes associated with schizophrenia and bipolar disorder across development," Transl Psychiatry, vol. 9, no. 1, p. 74, Feb 4 2019.

V. K. Ota et al., "Gene expression over the course of schizophrenia: from clinical high-risk for psychosis to chronic stages," NPJ Schizophr, vol. 5, no. 1, p. 5, Mar 28 2019.