School of Graduate and Interdisciplinary Studies, University of Louisville, Louisville, KY 40292, USA.
Department of Neuroscience Training, University of Louisville, Louisville, KY 40292, USA.
Genes (Basel). 2023 Nov 25;14(12):2125. doi: 10.3390/genes14122125.
While the role of G quadruplex (G4) structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on the alteration of the G4 secondary structure. A total of 37,515 G4 SNVs in the COSMIC database and 2378 in CLINVAR were identified. Of those, 7236 COSMIC (19.3%) and 457 (19%) of the CLINVAR variants result in G4 loss, while 2728 (COSMIC) and 129 (CLINVAR) SNVs gain a G4 structure. The remaining variants potentially affect the folding energy without affecting the presence of a G4. Analysis of mutational patterns in the G4 structure shows a higher selective pressure (3-fold) in the coding region on the template strand compared to the reverse strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter, and enhancer regions across strands.
虽然 G 四链体 (G4) 结构在癌症和代谢紊乱中发挥了作用，但单核苷酸变异 (SNV) 及其在疾病环境中对 G4 的影响尚未得到广泛研究。使用 COSMIC 和 CLINVAR 数据库来检测 G4 中存在的 SNV，以识别序列水平的变化及其对 G4 二级结构改变的影响。在 COSMIC 数据库中总共发现了 37515 个 G4 SNV，CLINVAR 中发现了 2378 个。其中，7236 个 COSMIC (19.3%) 和 457 个 CLINVAR (19%)的变体导致 G4 丢失，而 2728 个 (COSMIC) 和 129 个 (CLINVAR) 的 SNV 获得了 G4 结构。其余变体可能会影响折叠能而不影响 G4 的存在。对 G4 结构中的突变模式进行分析表明，模板链上的编码区域比反向链上的选择性压力高 3 倍。同时，在两条链上的内含子、启动子和增强子区域中观察到相同比例的 SNV。
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