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Abstract：
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.
摘要：
虽然已经确定了G四链体（G4）结构在癌症和代谢紊乱中的作用，单核苷酸变异（SNV）及其在疾病背景下对G4s的影响尚未得到广泛研究。COSMIC和CLINVAR数据库用于检测G4s中存在的SNV，以鉴定序列水平变化及其对G4二级结构改变的影响。在COSMIC数据库中总共确定了37,515G4SNV，在CLINVAR中确定了2378。其中,7236COSMIC（19.3％）和457（19％）的CLINVAR变体导致G4损失，而2728(COSMIC)和129(CLINVAR)SNV获得G4结构。其余的变体潜在地影响折叠能量而不影响G4的存在。G4结构中的突变模式的分析显示,与反向链相比,模板链上的编码区具有更高的选择压力(3倍)。同时,在内含子中观察到相等比例的SNV，启动子,和跨链的增强子区域。
