Discovery and verification of single nucleotide polymorphisms in GABAA̳ receptor subunit genes and association analysis with schizophrenia in Chinese

Abstract

Single Nucleotide Polymorphisms (SNPs) became a popular research topic in the study of complex diseases such as cancer, diabetes, mental illness and cardiovascular disease after the Human Genome Project was finished. Schizophrenia is a complex disease which has about 1% population prevalence. However, the etiopathogenesis of schizophrenia has not been determined. From clinical studies, the human GABA_A receptor gene was found to be a susceptible gene in schizophrenia. In this project, the focus is on the association between SNPs in α₁, γ₂, and ε subunit genes in human GABA_A receptor and schizophrenia, among Chinese schizophrenic patients and normal controls.

Ten SNPs were identified by two methods - ESTs-guided DNA sequencing and de novo sequencing. ESTs-guided DNA sequencing is based on resources from public database for SNP identification followed by experimental sequencing for verification. De novo DNA sequencing is based on traditional sequencing which is more accurate for SNP identification but much more time-consuming. Among the ten SNPs identified, three of them were non-synonymous cSNP, three of them were synonymous cSNP and the other four were located in the intron region. Results from the association analysis suggest that there were no association between these SNPs and schizophrenia. However, the two non-synonymous SNPs found in the γ₂ and ε subunits may be related to schizophrenia.

Date of Award	2002
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology