Identification of high-risk non-synonymous SNPs (nsSNPs) in DNAH1 and DNAH17 genes associated with male infertility: a bioinformatics analysis.

Abstract

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.