Kennedy James L, Farrer Lindsay A, Andreasen Nancy C, Mayeux Richard, St George-Hyslop Peter
Departments of Psychiatry and Medicine, Centre for Addiction and Mental Health, Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H9, Canada.
Science. 2003 Oct 31;302(5646):822-6. doi: 10.1126/science.1092132.
Genetic factors play a major role in the etiology of adult-onset neurodegenerative and neuropsychiatric disorders. Several highly penetrant genes have been cloned for rare, autosomal-dominant, early-onset forms of neurodegenerative diseases. These genes have provided important insights into the mechanisms of these diseases (often altering neuronal protein processing). However, the genes associated with inherited susceptibility to late-onset neurodegenerative diseases, schizophrenia, and bipolar disorder appear to have smaller effects and are likely to interact with each other (and with nongenetic factors) to modulate susceptibility and/or disease phenotype. Several strategies have recently been applied to address this complexity, leading to the identification of a number of candidate susceptibility loci/genes.
遗传因素在成人期神经退行性疾病和神经精神疾病的病因中起主要作用。已经克隆出了几个高外显率基因，用于研究罕见的、常染色体显性、早发型神经退行性疾病。这些基因已经为这些疾病的发病机制提供了重要见解（通常改变神经元蛋白质加工过程）。然而，与晚发型神经退行性疾病、精神分裂症和双相情感障碍的遗传易感性相关的基因，其作用似乎较小，并且可能相互作用（以及与非遗传因素相互作用）来调节易感性和/或疾病表型。最近已经应用了几种策略来应对这种复杂性，从而鉴定出了许多候选易感基因座/基因。
