Investigation of 7q36.1 (Chr7:150,150-150,355kb) region as a possible hot-spot susceptibility locus for schizophrenia by SNP genotyping and haplotype analysis.

The molecular genetic research of schizophrenia, a major psychosis that seems to be a complex disorder, has so far failed to reach a meaningful success. The present doctoral thesis study aims to elucidate, on the basis of an original hypothesis that we proposed following bioinformatic evaluation of findings disclosed by Huffaker et al [2009] and Atalar et al [2010] from our research group, whether the 7q36.1 (Chr7:150,150-150,355kb) region is a "hot-spot susceptibility locus" for schizophrenia, and which one(s) from four genes and one copy number variation (CNV) located on this region may be related with genetic susceptibility to schizophrenia. In this context, 24 single nucleotide polymorphisms (SNPs) systematically selected in 7q36.1 region were genotyped by quantitative real-time PCR (QRT-PCR) in 80 male patients with schizophrenia (case group) and in 80 male healthy individuals (control group). Following haplotyping and genotype (allele) and haplotype association analyses: (1) Statistically significant differences were determined between case and control groups in the distributions of allele frequencies of two consecutively located SNPs (rs4725379, rs12530905); (2) Statistically significant differences were determined between case and control groups in the distributions of haplotype frequencies in two consecutively located haplotype blocks (H2, H3) among the four haplotype blocks identified in 7q36.1 region. Thereby, (1) a genomic region including the entire HERG1 gene and a major part of the CNV_3711 and (2) a genomic region merely including a part of the CNV_3711 were disclosed to be two separate but consecutive susceptibility loci ("hot-spot susceptibility locus") associated with genetic susceptibility to schizophrenia in 7q36.1 region. In conclusion, the present doctoral thesis study has fully reached its goal and provided the answers of the targeted questions. Furthermore, the original findings revealed in the present study are well qualified to give rise to new interesting questions and thereby more advanced hypotheses. Key Words: schizophrenia, genotype, haplotype, 7q36.1, HERG1