Montgomery Stephen
Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
Methods Mol Biol. 2009;569:89-114. doi: 10.1007/978-1-59745-524-4_5.
Discovery of DNA sequence variants responsible for human phenotypic variation is key to advances in molecular diagnostics and medicines. Historically, variants that alter the protein-coding sequence of genes have been targeted when attempting to identify a trait's etiology; this is done because the rules governing these regions are generally well-understood and candidate variants can be easily selected. However, the effects of variants on gene regulation are increasingly regarded as being as important as protein-coding variation in uncovering the nature of phenotypic variation. I discuss resources and methodology that have recently been developed to computationally prioritize variants that may alter gene expression.
发现导致人类表型变异的DNA序列变体是分子诊断和医学进步的关键。从历史上看，在试图确定某一性状的病因时，会将改变基因蛋白质编码序列的变体作为目标；这样做是因为这些区域的调控规则通常已被充分理解，候选变体也很容易被挑选出来。然而，在揭示表型变异的本质方面，变体对基因调控的影响越来越被认为与蛋白质编码变异同样重要。我将讨论最近开发的资源和方法，这些资源和方法用于通过计算对可能改变基因表达的变体进行优先级排序。
