Yoganarasimha Bharath, Chandramohan Vivek, Krishna Murthy Thirupathihalli P, Gangadharappa Bhavya S, Siddaiah Gowrishankar B, Hanumanthappa Makari
Department of Biotechnology, M. S. Ramaiah Institute of Technology, Bengaluru, Karnataka, India.
Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, Karnataka, India.
J Taibah Univ Med Sci. 2016 Sep 27;12(3):221-228. doi: 10.1016/j.jtumed.2016.07.009. eCollection 2017 Jun.
The gene expresses a protein, G1/S-specific cyclin, that regulates the G1/S transition in the cell cycle and also inhibits retinoblastoma (RB) proteins. Overexpression or rearrangements of this gene can result in various tumours. This study aimed to identify possible deleterious non-synonymous single nucleotide polymorphisms (SNP's) of using computational methods.
SNPs in the human gene were retrieved from dbSNP. These SNPs were screened by the Sorting Intolerant From Tolerant (SIFT) algorithm and the PredictSNP classification. Mutants with deleterious SNPs were built using Discovery Studio 3.5, and dynamics studies were performed on native and mutant varieties.
In , 1194 SNPs were found, of which 94 were missense and 2 were nonsense SNPs. Three SNPs were found to be deleterious. Molecular dynamics and trajectory analysis showed that there was a significant deviation of the root mean square deviation (RMSD) values in the N216K mutant from the values of the native protein.
Based on this study, we propose that the SNP with SNP ID rs112525097 (NM_053056.2:c.648C>G) might cause aberrations in , which might lead to a change in the function of the G1/S-specific cyclin protein. This, in turn, may lead to the development of acute myeloid leukaemia (AML).
该基因表达一种蛋白质，即G1/S特异性细胞周期蛋白，它调节细胞周期中的G1/S转换，还抑制视网膜母细胞瘤（RB）蛋白。该基因的过表达或重排可导致各种肿瘤。本研究旨在使用计算方法鉴定可能有害的非同义单核苷酸多态性（SNP）。
从dbSNP中检索人类该基因中的SNP。这些SNP通过从耐受中筛选不耐受（SIFT）算法和PredictSNP分类进行筛选。使用Discovery Studio 3.5构建具有有害SNP的突变体，并对天然和突变变体进行动力学研究。
在该基因中发现了1194个SNP，其中94个是错义突变，2个是无义SNP。发现3个SNP是有害的。分子动力学和轨迹分析表明，N216K突变体的均方根偏差（RMSD）值与天然蛋白质的值存在显著偏差。
基于本研究，我们提出SNP ID为rs112525097（NM_053056.2:c.648C>G）的SNP可能导致该基因出现异常，这可能导致G1/S特异性细胞周期蛋白的功能发生变化。进而可能导致急性髓系白血病（AML）的发生。
