论文信息 - MicroRNA in schizophrenia: Genetic and expression analysis of miR-130b (22q11)

MicroRNA in schizophrenia: Genetic and expression analysis of miR-130b (22q11)

MicroRNAs (miRNAs) are a class of small regulatory RNAs that control a level of expression of protein encoding genes. Their role in brain pathologies is unknown. We made a first attempt to carry out a genetic study coupled with gene expression analysis of microRNA in human neuropsychiatric pathology. Presumably, at least one third of known miRNA genes are expressed in the brain. Mutations disrupting MECP2 protein lead to abnormal development of the brain and resulting behavior. MiR-130b expressed in the brain and potentially targeting MECP2 is located in the susceptibility locus for schizophrenia (22q11). We performed a comparative analysis of the expression of miR-130b in 24 brain neocortex samples from schizophrenic and normal individuals. The stability and effective detection of mature microRNA in postmortem tissues using Real-time PCR have been shown. Screening for mutations has identified a population polymorphism in the 5′-upstream miR-130b gene region containing DNA elements for putative transcription factors. Genetic association analysis of 300 schizophrenia and 316 normal control individuals revealed no statistically significant association of any of the miR-130b allelic variants with schizophrenia. The data demonstrated feasibility and perspective of convergent genetic and expression analysis of human microRNA genes in testing their role in human diseases.

[1] Anton J. Enright,et al. Materials and Methods Figs. S1 to S4 Tables S1 to S5 References and Notes Micrornas Regulate Brain Morphogenesis in Zebrafish , 2022 .

[2] R. Shprintzen,et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[3] Joel S Parker,et al. microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder , 2007, Genome Biology.

[4] Oliver Hobert,et al. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans , 2003, Nature.

[5] M. Owen,et al. High rates of schizophrenia in adults with velo-cardio-facial syndrome (VCFS) , 1999, Schizophrenia Research.

[6] V. Ambros. microRNAs Tiny Regulators with Great Potential , 2001, Cell.

[7] R. Weksberg,et al. 22q11 deletion syndrome in adults with schizophrenia. , 1998, American journal of medical genetics.

[8] L. Abramova,et al. Polymorphism in the 5′-promoter region of serine racemase gene in schizophrenia , 2006, Molecular Psychiatry.

[9] D. Cohen,et al. MECP2 mutation in a boy with language disorder and schizophrenia. , 2002, The American journal of psychiatry.

[10] E. I. Rogaev,et al. Small RNAs in Human Brain Development and Disorders , 2005, Biochemistry (Moscow).

[11] C. Burge,et al. Prediction of Mammalian MicroRNA Targets , 2003, Cell.