Investigation of putative candidate genes involved in the pathogenesis of Schizophrenia using a large Irish case-control sample

Abstract

This research thesis involved a candidate gene search for schizophrenia in the Irish population. It sought to identify candidate genes based on positional and functional information contained in previously published material. The pathogenesis of schizophrenia is currently unknown. However, two prominent theories are that of pathology during neurodevelopment and more recently the involvement of oxidative stress. Eight genes putatively involved in schizophrenia pathogenesis were investigated. Firstly, Dr. Aiden Corvin and I equally investigated the six genes in the Apolipoprotein-L (APOL) family. 1 looked at APOL-4, -5 and -6 while Dr. Corvin looked at APOL -1, -2 and -3. This family of genes were both functional and positional candidates as APOL-1, -2 and -4 were found to be significantly up- regulated in post-mortem schizophrenic brains (Mimmack et al 2002), located in a region previously identified in linkage studies and are located on chromosome 22q and some 15 Mb away from the Velo-cardio facial syndrome deletion region. Using public information from NCBI’s dbSNP database, 143 SNPs spanning the six genes were selected from 187 SNPs and initially genotyped in a DNA pool sample to confirm heterozygosity, of which 36% were. The 51 SNPs were genotyped in case and control DNA pools. Using a novel method for correcting pooled allele frequencies (McGhee et al 2005) 2 SNPs were identified for further analysis. After correction with true heterozygote frequencies, neither SNP showed association with schizophrenia.