Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Genome Biol. 2023 Jul 3;24(1):147. doi: 10.1186/s13059-023-02986-x.
Sequencing has revealed hundreds of millions of human genetic variants, and continued efforts will only add to this variant avalanche. Insufficient information exists to interpret the effects of most variants, limiting opportunities for precision medicine and comprehension of genome function. A solution lies in experimental assessment of the functional effect of variants, which can reveal their biological and clinical impact. However, variant effect assays have generally been undertaken reactively for individual variants only after and, in most cases long after, their first observation. Now, multiplexed assays of variant effect can characterise massive numbers of variants simultaneously, yielding variant effect maps that reveal the function of every possible single nucleotide change in a gene or regulatory element. Generating maps for every protein encoding gene and regulatory element in the human genome would create an 'Atlas' of variant effect maps and transform our understanding of genetics and usher in a new era of nucleotide-resolution functional knowledge of the genome. An Atlas would reveal the fundamental biology of the human genome, inform human evolution, empower the development and use of therapeutics and maximize the utility of genomics for diagnosing and treating disease. The Atlas of Variant Effects Alliance is an international collaborative group comprising hundreds of researchers, technologists and clinicians dedicated to realising an Atlas of Variant Effects to help deliver on the promise of genomics.
测序已经揭示了数亿个人类遗传变异，而且这一变异狂潮还在继续。由于大多数变异的影响信息不足，限制了精准医学的机会和对基因组功能的理解。解决方法在于对变异的功能效应进行实验评估，这可以揭示它们的生物学和临床影响。然而，变异效应检测通常是在个体变异被首次观察到之后，并且在大多数情况下是在很久之后才进行的，这是一种被动的方法。现在，大规模变异效应的多重检测可以同时对大量变异进行特征分析，生成变异效应图谱，揭示基因或调控元件中每个可能的单核苷酸变化的功能。生成人类基因组中每个蛋白质编码基因和调控元件的图谱，将创建一个变异效应图谱的“图谱集”，从而改变我们对遗传学的理解，开创基因组核苷酸分辨率功能知识的新时代。图谱集将揭示人类基因组的基本生物学，为人类进化提供信息，为治疗药物的开发和使用提供动力，并使基因组学在诊断和治疗疾病方面的应用最大化。变异效应图谱联盟是一个由数百名研究人员、技术专家和临床医生组成的国际合作组织，致力于实现变异效应图谱集，以帮助实现基因组学的承诺。
