| Abstract It is concluded that genetic factors contribute to schizophrenia after a large number of epidemiology studies for long term. Inheritance models involve oligogene inheritance with middle effect or multigene inheritance with very small effect. After linkage analysis failed to locate susceptible genes of complex diseases like schizophrenia, it is a better way to process whole-genome association studies. Hypotheses of dysfunction in serotonin and dopamine's systems are becoming more attractive with more and more supports from physiology and pharmacology studies. Association study (candidate gene approach) is one of the best strategies in finding functional polymorphisms of schizophrenia susceptible genes now, especially from those polymorphisms in serotonin and dopamine's receptor,transporter and metabolism enzyme genes. Single nucleotide polymorphism (SNP) is a new kind of genetic marker developed by recent years. And it become one of the most powerful tools in association study of complex diseases now, as the result of the advantages of high density,large number,well stability and easy to be detected.In this thesis we did an association study between psychiatric disorders and SERT gene, and found a VNTR polymorphism in the SERT gene showing association with schizophrenia and unipolar depression, but not with bipolar disorder in Chinese population. We also investigated the SNP profile of the SERT gene by re-sequencing the SERT gene in 204 individuals consisted of Chinese Han, Scottish Caucasian and other 9 minorities in China. A low degree of nucleotide diversity and a low level of linkage disequilibrium were observed from the SNP profile. The diversity of LD level and haplotypes distribution were demonstrated among different populations. An independent case-control study using several identified SNPs confirmed the association between SERT gene and schizophrenia, which added more evidence supporting the role of this gene played in psychiatric disorders. |
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