Kim Namshin, Lee Christopher
Molecular Biology Institute, Institute for Genomics and Proteomics, Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.
Methods Mol Biol. 2008;452:179-97. doi: 10.1007/978-1-60327-159-2_9.
In recent years, genome-wide detection of alternative splicing based on Expressed Sequence Tag (EST) sequence alignments with mRNA and genomic sequences has dramatically expanded our understanding of the role of alternative splicing in functional regulation. This chapter reviews the data, methodology, and technical challenges of these genome-wide analyses of alternative splicing, and briefly surveys some of the uses to which such alternative splicing databases have been put. For example, with proper alternative splicing database schema design, it is possible to query genome-wide for alternative splicing patterns that are specific to particular tissues, disease states (e.g., cancer), gender, or developmental stages. EST alignments can be used to estimate exon inclusion or exclusion level of alternatively spliced exons and evolutionary changes for various species can be inferred from exon inclusion level. Such databases can also help automate design of probes for RT-PCR and microarrays, enabling high throughput experimental measurement of alternative splicing.
近年来，基于表达序列标签（EST）与mRNA和基因组序列的比对进行的全基因组可变剪接检测，极大地拓展了我们对可变剪接在功能调控中作用的理解。本章回顾了这些全基因组可变剪接分析的数据、方法和技术挑战，并简要概述了此类可变剪接数据库的一些应用。例如，通过适当的可变剪接数据库模式设计，可以在全基因组范围内查询特定于特定组织、疾病状态（如癌症）、性别或发育阶段的可变剪接模式。EST比对可用于估计可变剪接外显子的外显子包含或排除水平，并且可以从外显子包含水平推断各种物种的进化变化。此类数据库还可以帮助自动设计用于RT-PCR和微阵列的探针，从而实现对可变剪接的高通量实验测量。
