Our genomes influence nearly every aspect of human biology—from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development of new diagnostic tools and therapeutic agents. Yet, understanding how genomic variation alters genome function to influence phenotype has proved challenging. To unlock these insights, we need a systematic and comprehensive catalogue of genome function and the molecular and cellular effects of genomic variants. Towards this goal, the Impact of Genomic Variation on Function (IGVF) Consortium will combine approaches in single-cell mapping, genomic perturbations and predictive modelling to investigate the relationships among genomic variation, genome function and phenotypes. IGVF will create maps across hundreds of cell types and states describing how coding variants alter protein activity, how noncoding variants change the regulation of gene expression, and how such effects connect through gene-regulatory and protein-interaction networks. These experimental data, computational predictions and accompanying standards and pipelines will be integrated into an open resource that will catalyse community efforts to explore how our genomes influence biology and disease across populations.

我们的基因组几乎影响着人类生物学的方方面面——从分子和细胞功能到健康和疾病的表型。研究个体之间 DNA 序列的差异（基因组变异）可以揭示以前未知的人类生物学机制，揭示疾病遗传易感性的基础，并指导新诊断工具和治疗剂的开发。然而，了解基因组变异如何改变基因组功能以影响表型已被证明具有挑战性。为了解锁这些见解，我们需要一个系统而全面的基因组功能目录以及基因组变异的分子和细胞效应。为了实现这一目标，基因组变异对功能的影响 （IGVF） 联盟将结合单细胞作图、基因组扰动和预测建模等方法，以研究基因组变异、基因组功能和表型之间的关系。IGVF 将创建数百种细胞类型和状态的图谱，描述编码变异如何改变蛋白质活性，非编码变异如何改变基因表达的调节，以及这些效应如何通过基因调控和蛋白质相互作用网络连接起来。这些实验数据、计算预测以及随附的标准和管道将被整合到一个开放资源中，该资源将促进社区努力探索我们的基因组如何影响不同人群的生物学和疾病。