Computational Analysis of High-Risk SNPs in Human DBY Gene Responsible for Male Infertility: A Functional and...

DEAD-box helicase 3, Y-linked (DBY) is a candidate gene of the AZF region which is involved in spermatogenesis process. Mutations in the DBY gene may disrupt the spermatogenesis and lead to infertility in men. Identification of functionally neutral mutation from the disease-causing mutation is the biggest challenge in human genetic variation analysis. Owing to the importance of DBY in male infertility, functional analysis was carried out to reveal the association between genetic mutation and phenotypic variation through various in silico approaches.

The present study analyzed the functional consequences of the nsSNPs in human DBY gene using SIFT, PolyPhen 2, PROVEAN, SNAP2, PMut, nsSNPAnalyzer, PhD-SNP and SNPs&GO along with stability analysis through I-Mutant2.0, MuPro and iPTREE-STAB. The conservational analysis of amino acid residues, biophysical properties and conserved domains of the DBY protein was analyzed using various computational tools. The 3D structure of the protein was generated using SPARKS-X and validated using RAMPAGE.

Out of 1130 SNPs reported in dbSNP, only one nsSNP (G300D) was found to have a functional effect on stability as well as the function of the DBY protein. The results showed the presence of G300 in the putative structure of DBY domain.

To the best of our knowledge, this is the first study to detect pathologically significant nsSNPs (G300D) through a computational approach in the DBY which can be useful for development in potent drug discovery studies.