Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, USA.
Bio-Techne, Minneapolis, Minnesota, USA.
Genome Biol. 2023 Feb 24;24(1):36. doi: 10.1186/s13059-023-02880-6.
Insertions and deletions (indels) enable evolution and cause disease. Due to technical challenges, indels are left out of most mutational scans, limiting our understanding of them in disease, biology, and evolution. We develop a low cost and bias method, DIMPLE, for systematically generating deletions, insertions, and missense mutations in genes, which we test on a range of targets, including Kir2.1. We use DIMPLE to study how indels impact potassium channel structure, disease, and evolution. We find deletions are most disruptive overall, beta sheets are most sensitive to indels, and flexible loops are sensitive to deletions yet tolerate insertions.
插入和缺失（indels）使进化成为可能，并导致疾病。由于技术挑战，indels 在大多数突变扫描中被忽略，限制了我们对其在疾病、生物学和进化中的理解。我们开发了一种低成本和无偏的方法 DIMPLE，用于系统地在基因中产生缺失、插入和错义突变，我们在一系列目标上进行了测试，包括 Kir2.1。我们使用 DIMPLE 研究 indels 如何影响钾通道结构、疾病和进化。我们发现总的来说缺失是最具破坏性的，β 片层对 indels 最敏感，柔性环对缺失敏感但能耐受插入。
