Background: Single nucleotide polymorphisms (SNPs) play a critical role in
influencing a person's susceptibility to diseases and in
determining how an
individual reacts to various treatment options. It is
crucial to differentiate and
characterize damaging SNPs from neutral ones and the aim of
this study was to
predict the deleterious SNPs of the lysozyme C (LYZ C) gene
via an in silico
analysis. LYZ C is an important antimicrobial peptide
capable of damaging the
peptidoglycan layer of bacteria leading to osmotic shock and
cell death.
Methods: The missense nonsynonymous SNPs (nsSNPs) of
the LYZ C gene were
subjected to different computational tools- SIFT, PolyPhen
v2, SNAP, PROVEAN,
PhD-SNP, and SNPs & GO. Deleterious SNPs as predicted by
these tools were
examined by I-Mutant 3.0 and ConSurf. GeneMANIA and STRING
tools were used
to study the interaction network of the LYZ C gene. The
impact of variations on the
structural characteristics of the protein was studied by
HOPE analysis. The
structures of variants and wild types were predicted by the
SWISS-MODEL web
server and the TM-align tool was used to predict the root
mean square deviation
(RMSD) and template modeling (TM) scores.
Results: Eight missense nsSNPs (T88N, I74T, F75I,
D67H, W82R, D85H, R80C,
and R116S) of the LYZ C gene were found to be potentially
deleterious. I-mutant
3.0 determined the variants that decreased the stability of
the protein. ConSurf
predicted rs121913547, rs121913549, and rs387906536 nsSNPs
to be conserved.
Interaction network tools showed that LYZ C protein
interacted with lactoferrin
(LTF). HOPE tool analyzed differences in physicochemical
properties between
wild type and variants. TM-align tool predicted the
alignment score and the protein
folding was found to be identical. PYMOL was used to
visualize the
superimposition of variants over wild types.
Conclusion: The present study ascertained the
deleterious missense nsSNPs of
the LYZ C gene and could be used in further experimental
analysis. These high
risk nsSNPs could be used as molecular targets for
diagnostic and therapeutic
interventions.
Author(s) Details
Harini Venkata Subbiah
Human Genetics Research Centre, Sree Balaji Dental College
and Hospital, Bharath Institute of Higher
Education and Research, Chennai, Tamil Nadu, 600100, India.
Dr. Usha Subbiah
Human Genetics Research Centre, Sree Balaji Dental College
and Hospital, Bharath Institute of Higher
Education and Research, Chennai, Tamil Nadu, 600100, India.
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