精神分裂症的分子遗传学研究进展

Progress in the studies on the molecular genetics of schizophrenia

群体遗传学研究表明 ,精神分裂症具有肯定的遗传倾向。现代分子生物学技术的发展使进一步寻找该病的易感基因成为可能。本文就国际近年来关于精神分裂症遗传研究的一些结果进行综述 :(1)该病遗传度约为 6 0 %～ 80 % ,标准化诊断及症状量表为主要的表型界定工具 ;(2 )基因组扫描及候选基因筛查为目前主要的研究手段 ,受累同胞对分析法 (affected sib- pair,ASP)及传递不平衡检验 (transmissiondisequilibrium test,TDT)为目前较理想的统计分析方法 ;(3)目前研究发现具有独立重复的阳性区域主要集中在 6 p、2 2 q和 8p,候选基因的阳性结果主要涉及 5 - HT2 A受体、DRD3及 NT- 3等。进一步研究途径包括 :更准确的表型界定、引入可靠的生物学标记、扩大样本量。

Although population genetic studies have long confirmed the genetic vulnerability of schizophrenia,ongoing advances in molecular genetic technology and biostatistic analysis are only now making it possible to search for the susceptibility gene of the disease. This article reviewed some of the recent findings in this area: (1) The heritability of schizophrenia is estimated around 60% 80%. The phenotype differentiation is based on standard diagnostic scales and symptom rating scales. (2) The two main approaches to finding the genes that influence the disorder are now genomic scan and candidate gene detection. Affected sib pair (ASP) method and transmission disequilibrium test(TDT) are considered promising analyses. (3) The positive candidate regions with some independent replicable reports concentrated on 6p, 22q and 8p. Positive findings of candidate gene research involved 5 HT2A receptor, DRD3, NT 3, etc. Further directions to identify the susceptibility genes include : Applying more precise instruments to define clinical phenotype of the disease. Application of proper biological markers such as electrophysiologic parameters and brain imaging will be a prospective approach.Using larger sample to increase statistic power and developing more powerful statistic analysis, and performing advanced molecular genetic technique such as DNA pooling, DNA chips, genomic mismatch scanning (GMS), representational difference analysis(RDA), comparative genomic hybridization(CGH) and two dimensional DNA typing methods will also facilitate this research area to greater perspective.