Modern molecular genetic approaches to complex traits: implications for psychiatric disorders.
Modern molecular genetic approaches to complex traits: implications for psychiatric disorders.
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现代分子遗传学方法处理复杂性状：对精神疾病的影响。
作者：
M. Owen;N. Craddock
大多数常见的精神疾病给遗传学家带来了问题，因为它们的遗传方式复杂且非孟德尔式。早期的精神疾病基因图谱的尝试到目前为止在很大程度上忽略了这一点，并使用连锁分析的lod评分方法在多重家庭中寻找主要影响基因。然而，似乎主基因最多也只是普通精神障碍的罕见原因，大多数病例可能反映了几个甚至许多影响相对较小的基因的相互作用。有两套互补的策略可以识别这些基因。第一种方法是根据患病亲属的等位基因共享情况进行连锁分析。二是对无关个体样本进行关联研究。这些方法及其适用性精神疾病的描述。精神病遗传学传统上集中在分类表型，但如果有效的连续措施可以开发，强大的数量性状基因座（QTL）的方法也可能成为可行的。另一个重要的领域可能是研究啮齿动物等动物的相关模型，其中遗传研究具有许多优势。最后，我们不应该忽视这样一种可能性，即对不规则的传播模式有分子解释，如线粒体遗传、基因组印记和动态突变。
The majority of common psychiatric disorders pose problems for geneticists because of their complex and non-Mendelian modes of inheritance. Early attempts to map genes for mental illness have so far largely overlooked this and sought genes of major effect in multiplex families using the lod score method of linkage analysis. However it seems that major genes are likely to be at best rare causes of common mental disorders, and the majority of cases probably reflect the interaction of several and perhaps many genes of comparatively small effect. There are two complementary sets of strategies that allow such genes to be identified. The first is to perform linkage analysis based on allele sharing in pairs of affected relatives. The second is to carry out association studies on samples of unrelated individuals. These methods and their applicability to psychiatric disorders are described. Psychiatric genetics has traditionally focussed on categorical phenotypes, but if valid continuous measures can be developed, powerful quantitative trait loci (QTL) approaches may also become feasible. Another important area is likely to be the study of relevant models in animals such as rodents in which genetic studies have many advantages. Finally we should not overlook the possibility that there are molecular explanations for irregular patterns of transmission such as mitochondrial inheritance, genomic imprinting and dynamic mutations.