International Journal of Genetic Engineering 2020, 8(1): 1-6
DOI: 10.5923/j.ijge.20200801.01
Computational Analysis of Single Nucleotide
Polymorphism (SNPs) in Human MYOC Gene
Amged Mohammed Ibrahim, Afra M. Albakry, Nuha Widat Alla, Mona A. M. Khaeir, Hind. A. Elnasri
*
Department of Molecular Biology and Bioinformatics, College of Veterinary Medicine, University of Bahri, Khartoum, Sudan
Abstract Glaucoma is a disease that damages the eye’s optic nerve. It usually occurs when fluid builds up in the front part
of the eye thus increasing the pressure within the eye and damaging the optic nerve. Among the causes of glaucoma is genetic
polymorphisms of MYOC gene which can alter the myocilin protein and thus disrupting the regulation of the intraocular
pressure which may lead to the disease. This study aimed to analyze nsSNPS in the Myocilin (MYOC) gene and the effect
they may have on the protein function and structure. SNPs were obtained from the NCBI dbSNP database. The nsSNPs were
further analyzed using 8 prediction tools namely GeneMANIA, SIFT, Polyphen-2, PROVEAN, SNPs & GO, PHD SNP,
I-Mutant 3.0 and Project Hope. GeneMANIA results showed the association of MYOC gene with 20 other genes and mainly
genes sharing the same protein domain. A total of 16 SNPs were predicted to be disease-associated using all software. Three
SNPs were found to increase protein stability while 13 SNPs decreased the stability of the protein. In the current study, some
SNPs that were previously reported to be associated with glaucoma were also found to be disease related using different
software, while other new SNPs were predicted for the first time. In the future, these SNPs can clinically be tested to
investigate their association with the disease.
Keywords In silico analysis, MYOC gene, Glaucoma, Bioinformatics
1. Introduction
Glaucoma is a complex, heterogeneous ocular disorder
with multi factorial etiology characterized by structural
damage to the optic nerve, and commonly associated with
relatively high intraocular pressure (IOP) [1-2]. It is a
leading cause of irreversible blindness worldwide with ~20%
of cases occurring secondary to other ocular or systemic
diseases [2-4].
Based on anatomical changes in the anterior chamber
angle, primary glaucoma may be classified as primary angle
closure glaucoma (PACG) or primary open-angle glaucoma
(POAG), which may be further subdivided into juvenile
open-angle glaucoma (JOAG) and adult onset POAG [1,5].
Glaucoma is a treatable disease if detected early; however,
many patients are diagnosed during routine examinations
or only following advanced field loss, as glaucoma is
typically asymptomatic in the early stages. Therefore,
the development of an accurate test for the detection of
presymptomatic carriers at risk is important for the
management of glaucoma.
* Corresponding author:
hindnasri2017@gmail.com (Hind. A. Elnasri)
Published online at http://journal.sapub.org/ijge
Copyright © 2020 The Author(s). Published by Scientific & Academic Publishing
This work is licensed under the Creative Commons Attribution International
License (CC BY). http://creativecommons.org/licenses/by/4.0/
A family history of glaucoma is a well-known risk factor
and hence genetic background is considered an important
factor for the development of the disease [6-8].
Several genes have been reported to be associated with
primary glaucoma including myocilin (MYOC), WD repeat
domain, neurotrophin 1, cytochrome P450 family 1 subtype
[9-10]. To date, mutations in these genes account for only
~5% of patients with POAG, and the influence of mutations
in these genes on patients with PACG remain controversial
[11-12].
The MYOC gene, is located on chromosome 1q24.3-q25.2.
Mutations in the gene are commonly found in juvenile or
early adult patients with high IOP although mutation
frequencies vary between ethnic groups [13].
Bioinformatics is now playing a key role in different
scientific areas. It involves computer sciences, mathematics,
and statistics in order to analyze biological data that is being
produced through the different sequencing techniques. Bio
computing plays a key role in understanding the implication
of genomic variations, especially single-nucleotide
polymorphisms (SNPs), which represent the most frequent
genetic variations in the human genome [14].
SNPs are the single base change in coding or non-coding
DNA sequence and are present in every 200-300 bp in
human genome [15]. The nonsynonymous SNPs (nsSNPs)
are the single nucleotide variations that affect the coding
region of the protein and modify the mutated site-encoded
amino acid, which may lead to a structural modification of