S80NRG1 isoform expression from human derived precursor neuronal cells, astrocytes and neurons from subjects with the NRG1 p.V266l genetic variant
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| Autores: | , , , |
|---|---|
| Formato: | actas de congreso |
| Fecha de Publicación: | 2019 |
| Descripción: | Background: Neuregulin 1 (NRG1) is an important risk gene in schizophrenia. A previous study found that the variant p.V266L (rs74942016, risk allele: T), in the transmembrane domain of NRG1, is associated with schizophrenia in the Costa Rican population. However, knowledge about the expression of NRG1 isoforms at a cellular level in human central nervous system is still limited. For this reason, we studied the expression of NRG1 isoforms in three human derived neural cell types, to evaluate the effect of the p.V266L variant on neuregulin expression. Methods: We used induced pluripotent stem cells (iPSCs) from lymphoblastoid cell lines (using Episomal-iPSC Reprogramming Kit) of subjects with and without the variant to produce neuronal precursor cells (NPCs), astrocytes and neurons. The variant is heterozygous in five subjects, homozygous in two subjects, and is absent in six subjects. Gene expression of the isoforms was examined using RNAseq. Results: We detected expression of six types of NRG1 isoforms (I to IV) and three additional ARN transcripts that were not grouped in any of those. We found that the expression of NRG1 isoforms varies in different cell types but there were no statistically significant differences between cells of subjects carrying at least one T allele compared to cells of subjects homozygous for the G allele. The type III isoform showed a higher expression in neurons than in the other two cell types, which is agreement with previous reports in human brain tissue. Discussion: Our results suggest that the expression of type I and type III NRG1 isoforms depends on the cell type, therefore, these results are also in agreement with our hypothesis that the variant affects the protein structure (in each cell type), but not the gene expression. Although the difference in isoform expression between genotypes was not significant in the models for isoforms type I and type III, there are slight changes in the isoform expression when the T allele is present. In order to confirm that the presence of the risk allele is not generating a difference in the expression levels of the neuregulin isoforms, it is necessary to replicate the present study with a larger sample. If there is in fact an effect of the variant in the NRG1 gene on isoform expression, our data suggests that this effect could potentially vary in the different cell types. |
| País: | Kérwá |
| Institución: | Universidad de Costa Rica |
| Repositorio: | Kérwá |
| Lenguaje: | Inglés |
| OAI Identifier: | oai:kerwa.ucr.ac.cr:10669/100178 |
| Acceso en línea: | https://hdl.handle.net/10669/100178 https://doi.org/10.1016/j.euroneuro.2019.08.081 |
| Palabra clave: | NRG1 isoform expression NRG1 p.V266L |