PIPK2A, a candidate gene for schizophrenia: impact of DNA polymorphisms on gene- and protein expression and -function

点击翻译按钮获取中文摘要

Schizophrenia is a devastating mental disorder with severe impact not only on the individual, but also on families and communities. Prevalence of the illness is worldwide about 0.5% for all populations. More than 200,000 Australians suffer from schizophrenia, costing the Australian community nearly $2 billion each year. The causes for schizophrenia are still unclear. There is now agreement that nature (genetic factors) and nurture (environmental influences) play a role in the development of the disorder. Evidence for genetic factors has been obtained and consistently confirmed by family-, twin-, and adoption studies. After many years of research, evidence for several genes, conferring susceptibility to schizophrenia, has been obtained by gene finding approaches applied to large family samples with multiple affected members. However, these genes have to be considered as candidates until more is known about their impact on brain function resulting in schizophrenic disorders. We have dissected a gene locus on chromosome 10p detected by linkage analysis by several groups including ourselves. We obtained statistical evidence for association of DNA sequence variants in the gene encoding the enzyme phosphatidyl-4-phosphate 5-kinase with schizophrenia. This enzyme is a critical component of the phosphoinositide pathways, which are involved in cell signalling. Our aim is to identify a possible dysfunction in the pathways. We will search for mutations involved in function or dysfunction of the enzyme. We will investigate gene- and protein expression and enzyme function in lymphoblast cell cultures and in post mortem brain tissue. Our ultimate goal is to characterise the possible impairment of intracellular cell signalling and thus identify molecular targets for development of novel and specific pharmacological treatments that have the potential to replace the currently available medication which is symptom-oriented and usually accompanied by severe adverse effects.