Tabet Daniel, Parikh Victoria, Mali Prashant, Roth Frederick P, Claussnitzer Melina
Donnelly Centre, Department of Molecular Genetics, and Department of Computer Science, University of Toronto, Toronto, Ontario, Canada; email:
Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.
Annu Rev Genet. 2022 Nov 30;56:441-465. doi: 10.1146/annurev-genet-072920-032107. Epub 2022 Sep 2.
Scalable sequence-function studies have enabled the systematic analysis and cataloging of hundreds of thousands of coding and noncoding genetic variants in the human genome. This has improved clinical variant interpretation and provided insights into the molecular, biophysical, and cellular effects of genetic variants at an astonishing scale and resolution across the spectrum of allele frequencies. In this review, we explore current applications and prospects for the field and outline the principles underlying scalable functional assay design, with a focus on the study of single-nucleotide coding and noncoding variants.
可扩展的序列-功能研究已能够对人类基因组中数十万种编码和非编码基因变异进行系统分析和编目。这改进了临床变异解读，并在从低频到高频的等位基因频率范围内，以前所未有的规模和分辨率提供了关于基因变异的分子、生物物理和细胞效应的见解。在本综述中，我们探讨了该领域的当前应用和前景，并概述了可扩展功能测定设计的基本原则，重点是单核苷酸编码和非编码变异的研究。
