Most disease-associated variants, although located in putatively regulatory regions, do not have detectable effects on gene expression. One explanation could be that we have not examined gene expression in the cell types or conditions that are most relevant for disease. Even large-scale efforts to study gene expression across tissues are limited to human samples obtained opportunistically or postmortem, mostly from adults. In this review we evaluate recent findings and suggest an alternative strategy, drawing on the dynamic and highly context-specific nature of gene regulation. We discuss new technologies that can extend the standard regulatory mapping framework to more diverse, disease-relevant cell types and states.

大多数与疾病相关的变异，虽然位于假定的调节区域，但对基因表达没有可检测的影响。一种解释可能是我们没有检查与疾病最相关的细胞类型或条件中的基因表达。即使是研究跨组织基因表达的大规模努力也仅限于机会主义或死后获得的人类样本，主要来自成年人。在这篇综述中，我们评估了最近的发现并提出了一种替代策略，利用基因调控的动态和高度特定于背景的性质。我们讨论了可以将标准监管映射框架扩展到更多样化、与疾病相关的细胞类型和状态的新技术。