Population-scale sequencing efforts have catalogued substantial genetic variation in humans such that variant discovery dramatically outpaces interpretation. We discuss how single-cell sequencing is poised to reveal genetic mechanisms at a rate that may soon approach that of variant discovery. The functional genomics toolkit is sufficiently modular to systematically profile almost any type of variation within increasingly diverse contexts and with molecularly comprehensive and unbiased readouts. As a result, we can construct deep phenotypic atlases of variant effects that span the entire regulatory cascade. The same conceptual approach to interpreting genetic variation should be applied to engineering therapeutic cell states. In this way, variant mechanism discovery and cell state engineering will become reciprocating and iterative processes towards genomic medicine.

群体规模的测序工作已经对人类的大量遗传变异进行了分类，因此变异的发现速度远远超过了解释速度。我们讨论单细胞测序如何以可能很快接近变异发现的速度揭示遗传机制。功能基因组学工具包足够模块化，可以在日益多样化的背景下系统地分析几乎任何类型的变异，并具有分子全面和公正的读数。因此，我们可以构建跨越整个调控级联的变异效应的深层表型图谱。解释遗传变异的相同概念方法应该应用于工程治疗性细胞状态。这样，变异机制发现和细胞状态工程将成为基因组医学的往复和迭代过程。