男性不育是一个重要的生殖问题,影响着全世界相当多的夫妇。虽然男性不育的原因有很多,遗传因素在其发展中起着至关重要的作用。我们专注于识别和分析DNAH1和DNAH17基因中的高风险nsSNPs,编码与精子运动有关的蛋白质。使用包括SIFT在内的各种生物信息学工具分析了DNAH1的20nsSNPs和DNAH17的10nsSNPs。PolyPhen-2,CADD,博士-SNPg,VEST-4和MutPred2。因此,V1287G,L2071R,R2356W,R3169C,R3229C,E3284K,R4096L,R4133C,DNAH1基因中的A4174T和C1803Y,C1829Y,R1903C,DNAH17基因中的L3595P被鉴定为高风险nsSNP。预测这些nsSNP会降低蛋白质稳定性,几乎所有的氨基酸都被发现在高度保守的氨基酸位置。此外,观察到4个nsSNP改变翻译后修饰状态。此外,相互作用网络分析显示DNAH1和DNAH17与DNAH2,DNAH3,DNAH5,DNAH7,DNAH8,DNAI2,DNAAL1,CFAP70,DNAI3,DNAI4,ODAD1和DNAI7相互作用,证明了DNAH1和DNAH17蛋白在精子运动机制整体功能中的重要性.一起来看,这些发现揭示了已鉴定的高危nsSNPs对蛋白质结构和功能的不利影响,并强调了它们与男性不育的潜在相关性.需要进一步的研究来验证这些发现并阐明潜在的机制。
Male infertility is a significant reproductive issue affecting a considerable number of couples worldwide. While there are various causes of male infertility, genetic factors play a crucial role in its development. We focused on identifying and analyzing the high-risk
nsSNPs in DNAH1 and DNAH17 genes, which encode proteins involved in sperm motility. A total of 20
nsSNPs for DNAH1 and 10
nsSNPs for DNAH17 were analyzed using various bioinformatics tools including SIFT, PolyPhen-2, CADD, PhD-SNPg, VEST-4, and MutPred2. As a result, V1287G, L2071R, R2356W, R3169C, R3229C, E3284K, R4096L, R4133C, and A4174T in DNAH1 gene and C1803Y, C1829Y, R1903C, and L3595P in DNAH17 gene were identified as high-risk nsSNPs. These
nsSNPs were predicted to decrease protein stability, and almost all were found in highly conserved amino acid positions. Additionally, 4
nsSNPs were observed to alter post-translational modification status. Furthermore, the interaction network analysis revealed that DNAH1 and DNAH17 interact with DNAH2, DNAH3, DNAH5, DNAH7, DNAH8, DNAI2, DNAL1, CFAP70, DNAI3, DNAI4, ODAD1, and DNAI7, demonstrating the importance of DNAH1 and DNAH17 proteins in the overall functioning of the sperm motility machinery. Taken together, these findings revealed the detrimental effects of identified high-risk
nsSNPs on protein structure and function and highlighted their potential relevance to male infertility. Further studies are warranted to validate these findings and to elucidate the underlying mechanisms.