Project 3

Assessing the role of Phophatidylinositol-4-phosphate-5-kinase gene (PIP5K2A) in schizophrenia through expression studies

Background

Schizophrenia is a devastating mental disorder affecting approximately 1% of the population worldwide. Evidence for participation of genetic factors has been obtained by family-, twin-, and adoption studies.

Our goal is the identification and characterization of genes conferring risk to schizophrenia.

Involvement of PIP5K2A in schizophrenia is based on previous association studies indicating that specific variants are associated with schizophrenia in at least one family sample.

Aims and experimental design

The aim of the project is to study alterations of gene expression of the PIP5K2A gene in cell cultures and post mortem brain tissue of schizophrenics.

RNA from lymphocyte cell lines and post mortem brain tissue from affected and unaffected individuals of the associated family sample will be used for cDNA preparation. These samples will be subjected to real time PCR using primers to generate products which bridge an intron in order to rule out amplification of genomic sequences. Since some of the associated DNA sequence variants may influence RNA splicing by creating new or abolishing existing recognition sites, it is planned to analyze several RNA preparations for differences in splice variants. Results for both approaches will be correlated with the DNA sequence variants in LD with schizophrenia.

Significance

We expect to gain insights into the pathophysiology of schizophrenia by studying gene expression of a gene where genetic variations have been found to be associated.

The intention of our research is to contribute to the identification of molecular causes for schizophrenia, and thus provide new targets for development of novel pharmacological treatment.