Hatten Mary E, Heintz Nathaniel
Laboratory of Developmental Neurobiology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Annu Rev Neurosci. 2005;28:89-108. doi: 10.1146/annurev.neuro.26.041002.131436.
Over the past two decades, molecular genetic studies have enabled a common conceptual framework for the development and basic function of the nervous system. These studies, and the pioneering efforts of mouse geneticists and neuroscientists to identify and clone genes for spontaneous mouse mutants, have provided a paradigm for understanding complex processes of the vertebrate brain. Gene cloning for human brain malformations and degenerative disorders identified other important central nervous system (CNS) genes. However, because many debilitating human disorders are genetically complex, phenotypic screens are difficult to design. This difficulty has led to large-scale, genomic approaches to discover genes that are uniquely expressed in brain circuits and regions that control complex behaviors. In this review, we summarize current phenotype- and genotype-driven approaches to discover novel CNS-expressed genes, as well as current approaches to carry out large-scale, gene-expression screens in the CNS.
在过去二十年中，分子遗传学研究为神经系统的发育和基本功能建立了一个通用的概念框架。这些研究，以及小鼠遗传学家和神经科学家为鉴定和克隆自发小鼠突变体的基因所做的开创性工作，为理解脊椎动物大脑的复杂过程提供了一个范例。针对人类脑畸形和退行性疾病的基因克隆鉴定出了其他重要的中枢神经系统（CNS）基因。然而，由于许多使人衰弱的人类疾病在遗传上很复杂，因此难以设计表型筛选。这一困难导致了大规模的基因组方法来发现那些在控制复杂行为的脑回路和区域中特异性表达的基因。在这篇综述中，我们总结了当前基于表型和基因型驱动的发现新的中枢神经系统表达基因的方法，以及目前在中枢神经系统中进行大规模基因表达筛选的方法。
