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

Interdisciplinary Sciences: Computational Life Sciences volume 11, pages 412–427 (2019)Cite this article

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Abbreviations

DBY :

DEAD-box helicase 3, Y-linked

SNPs:

Single nucleotide polymorphisms

nsSNPs:

Non-synonymous SNPs

dbSNP:

Database of SNP

3′UTR:

Three prime untranslated region

5′UTR:

Five prime untranslated region

OMIM:

Online Mendelian Inheritance in Man

NCBI:

National Center for Biotechnology Information

SIFT:

Sorting intolerant from tolerant

PolyPhen-2:

Polymorphism phenotyping v2

PROVEAN:

Protein Variation Effect ANalyzer

PDB:

Protein Data Bank

SNPs&GO:

Single nucleotide polymorphisms and gene ontology

PhD-SNP:

Predictor of human deleterious single nucleotide polymorphisms

TI:

Tolerance index

STRING:

Search tool for the retrieval of interacting genes/proteins

SVM:

Support vector machine

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Acknowledgements

The authors express appreciation to Charutar Vidya Mandal (CVM) and SICART, Vallabh Vidyanagar, Gujarat, for providing research work platform. We acknowledge Director, Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), New Vallabh Vidynagar for all the facilities and constant encouragements to carry out this work. This work was supported by INSPIRE division of the Department of Science and Technology in the form of research fellowship to Ms. Mili Nailwal.

Funding

This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

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  1. P.G. Department of Genetics, Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), New Vallabh Vidyanagar, Dist-Anand, Gujarat, 388121, India

    Mili Nailwal & Jenabhai B. Chauhan

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  1. Mili Nailwal
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Correspondence to Jenabhai B. Chauhan.

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Mili Nailwal is the first author.

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Nailwal, M., Chauhan, J.B. Computational Analysis of High-Risk SNPs in Human DBY Gene Responsible for Male Infertility: A Functional and Structural Impact. Interdiscip Sci Comput Life Sci 11, 412–427 (2019). https://doi.org/10.1007/s12539-018-0290-7

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Keywords

  • Male infertility
  • DBY
  • Computational analysis
  • Non-synonymous SNPs
  • Single nucleotide polymorphism