See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/330016204

S Single Nucleotide Polymorphism (SNP)

Chapter · December 2018

DOI: 10.1007/978-3-319-47829-6_2049-1

CITATION READS

1 685

3 authors, including:

Runjhun Mathur Abhimanyu Kumar Jha

Institute of Applied Medicines & Research Sharda University
25 PUBLICATIONS   12 CITATIONS    95 PUBLICATIONS   357 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Epigenetics View project

Alzheimer's Disease View project

All content following this page was uploaded by Abhimanyu Kumar Jha on 31 December 2018.

The user has requested enhancement of the downloaded file.

S

Single Nucleotide place of guanine (G) in a stretch of DNA. SNPs, if

Polymorphism (SNP) falling under coding region of genes, do not alter
the amino acid sequence and, in turn, the sequence
Runjhun Mathur1, Bhisham Singh Rana1 and of protein produced. They are classified into two
Abhimanyu Kumar Jha1,2 parts: synonymous, i.e., genes that do not bring
1
Department of Biotechnology, IMS Engineering any change in protein, and nonsynonymous, i.e.,
College, Ghaziabad, UP, India genes that bring change in amino acid sequence,
2
Department of Biotechnology, Institute of which may be a missense (resulting in incorrect
Applied Medicine & Research, Ghaziabad, UP, amino acid) or nonsense (not coding for any
India amino acid).
SNP density of existence can be predicted by
the sequence known as microsatellites. The most
Synonyms common predictor of density is “AT” micro-
satellites. SNPs are also classified on the basis of
Point mutation their regions, i.e., noncoding and coding regions.
Coding regions can be further classified as mis-
sense and nonsense regions. SNPs represent 90%
Definition of the total variations, which means that the
genetic variation occurring on a daily basis is
SNPs are single nucleotide changes in genomic caused by small change in nucleotide.
DNA at which different nucleotides occur in dif-
ferent individuals of a population. Each nucleo-
tide at such a position denotes an allele of the SNP. Identification

Single base variants in cDNA are considered as

Introduction SNPs, as are single base insertions and deletions
in the genome. Several different methods have
Single nucleotide polymorphisms (SNPs), pro- been developed to discover SNPs. A simple pro-
nounced as “Snips,” is the common type of vari- cedure is to analyze the sequence data stored in the
ation found in DNA between genes (Genetics major databases and identify the SNPs. DNA
Home Reference). Each SNP differs by a single chips/microarray has been developed for SNPs
DNA block represented as nucleotide. For exam- identification. When the complete base sequence
ple, a SNP may be replaced by adenine (A) in of a segment of DNA is considered, one can
# Springer International Publishing AG, part of Springer Nature 2018
J. Vonk, T. K. Shackelford (eds.), Encyclopedia of Animal Cognition and Behavior,
https://doi.org/10.1007/978-3-319-47829-6_2049-1
2 Single Nucleotide Polymorphism (SNP)
identify four alleles represented by A, T, G, and
C at each SNP locus in the segment.
It is estimated that approximately 90% of
sequence variation in human is due to SNPs. Our
genome is estimated to contain 3–17 million
SNPs. Of these, 5% of SNPs are expected to
occur in genes. Thus, SNPs provide a molecular
marker that occurs in genome at a very high den-
sity and can therefore be used to map genes
involved in human diseases.
Efforts are being made to use SNPs to map
hundreds or thousands of genes that have an effect
on the safety and efficacy of various drug treat-
ments. These SNPs can be placed on gene chips
that can be used to genotype individuals for those
genes involved in response to specific drugs.
Based on this data, more efficacious and safe
treatment can be selected for these individuals.
For example, variants in the gene encoding apoli-
poprotein E were found to be correlated with
variation in response to a drug used for treatment.
Gene apoE is involved in susceptibility to
Alzheimer’s disease, and a cholinesterase inhibi-
tor is used to mitigate the disease symptoms
(Wilkinson et al. 2004).
Diseases
SNPs can be treated as a biomarker for different
diseases like sickle cell anemia, b-thalassemia,
and cystic fibrosis. Heart disease, diabetes, and
cancer can also be correlated with SNPs. They
work in coordination with other SNPs to produce
a disease condition like in osteoporosis (Singh
et al. 2010). Higher risk of cancer is associated
with SNPs in noncoding regions, and mRNA
structure and disease susceptibility may be
affected. Such synonymous substitutions do not
result in a change of amino acid in the protein but
can still affect its function in other ways. For
example, multidrug resistance gene 1 (MDR1)
can cause the mutant pump to be less functional
(Kimchi et al. 2007).
Nonsynonymous substitutions include mis-
sense in which single change in the base results
in a change in an amino acid of protein and its
malfunction leads to disease (e.g., c.1580G>T
SNP in LMNA gene mandibuloacral dysplasia
and progeria syndrome, Al-Haggar et al. 2012)
and nonsense, which includes a premature stop
codon or a nonsense codon in the transcribed
mRNA. A usually nonfunctional protein product
is obtained if point mutation occurs in a sequence
of DNA (e.g., cystic fibrosis caused by the muta-
tion of G542X in the cystic fibrosis transmem-
brane conductance regulator gene, Cordovado
et al. 2012).
Importance of SNPs
Human genetic variation occurs primarily by
SNPs occurring in protein coding regions, which
contribute to different phenotypic variations. SNP
(rs2596542C/T) in major compatibility genes can
be used as a good potential biomarker in assess-
ment of liver disease (Mohamed et al. 2017).
SNPs are critical in predicting prostate cancer
risk. Studies suggest that there is strong dose-
dependent association. SNPs provide the way for
therapeutic targets. SNPs are also found to be very
useful biomarkers in plant breeding and genome
analysis. Eleven SNPs are found to be reported at
nine loci for gastric cancer risk.
Examples Are as Follows
(a) Serotonin 5-HT2A receptor gene rs6311 and
rs6313 are SNPs on human chromosome
13 (Giegling et al. 2006).
(b) Leiden thrombophilia was caused by Factor
V in the F5 gene in SNPs (Kujovich 2011).
(c) CRP gene on human chromosome
1 rs3091244 is an example of a triallelic
SNP (Morita et al. 2007).
(d) DNA mismatch repair gene PMS2
(rs1059060, Ser775Asn) is an intronic SNP
and is associated with increased sperm DNA
damage and risk of male infertility
(Ji et al. 2012).
Single Nucleotide Polymorphism (SNP)
Databases
SNP database named dbSNP is from the National
Center for Biotechnology Information (NCBI).
Till 8 June 2015, dbSNP identified 149,735,377
SNPs in humans. Kaviar is an anthology of SNPs
from multiple data sources including dbSNP
(Glusman et al. 2011). OMIM database (diseases
are represented in text form) dbSAP – single
amino-acid polymorphism database – is used
(Cao et al. 2016).
Programs for Prediction of SNPs
A change in amino acids with almost similar size
and physicochemical properties (e.g., substitution
from glycine to alanine) has a mild effect. SNP
can disrupt secondary structure elements (e.g.,
substitution to proline in an alpha helix region),
and such mutation usually may affect the whole
protein structure and function. Therefore, a group
of programs for the prediction of SNP effect was
developed which includes SIFT, SNAP2, SuS-
Pect, PolyPhen-2, Predict SNP, Mutation Taster:
official website, and Variant Effect Predictor from
the Ensembl Project (Wei et al. 2010).
Evolutionary Relationship
Variations occurring in a human population in the
SNP allele, common to one geographical area,
will rarely be found in another. Therefore, for a
population, SNPs can have a minor allele fre-
quency, and the lowest allele frequency at a
locus can be observed in a particular population.
Therefore, SNPs can be used in an investigation or
study of any migration patterns.
Conclusion
SNPs occurring in different populations help in
better understanding the metabolism of lipids and
thus reducing the cardiac risk. Polymorphism
associated with LDL correlated with lipid metab-
olism is associated with reduction in rate of
3
myocardial infarction. The clinical setting and
evaluation of polymorphism in different
populations will play a role in the future for cor-
onary artery disease. SNPs can be used as genetic
biomarkers for the family Brassicaceae. The spe-
cies named B. rapa was used to successfully
genotype the Brassicaceae, and many more
markers are genotyped. SNPs are acting as a key
to unlock the mystery. With advancement in fields
like biotechnology, many of the so-called myster-
ies have been resolved, which help in prevention
and treatment of various diseases and will ulti-
mately lead to the discovery of new drugs, which
can increase the average life span of human
beings. Living conditions and human lifestyles
are improving day by day; therefore, with the
advancement in biotechnology, safer anticancer
drugs will come.
Cross-References
▶ Allele
▶ Base Pair
▶ Targeted Mutation
References
Al-Haggar, M., Madej-Pilarczyk, A., Kozlowski, L.,
Bujnicki, J. M., Yahia, S., Abdel-Hadi, D., Shams, A.,
Ahmad, N., Hamed, S., & Puzianowska-Kuznicka,
M. (2012). A homozygous p.Arg527Leu LMNA muta-
tion in the two unrelated Egyptian families causes over-
lapping mandibuloacral dysplasia and progeria
syndrome. European Journal of Human Genetics, 20,
1134–1140.
Cao, R., Shi, Y., Chen, S., Ma, Y., Chen, J., Yang, J., Chen,
G., & Shi, T. (2016). dbSAP: Single amino-acid poly-
morphism database for protein variation detection.
Nucleic Acids Research, 45, 827–832.
Cordovado, S. K., Hendrix, M., Greene, C. N., Mochal, S.,
Earley, M. C., Farrell, P. M., Kharrazi, M., Hannon,
W. H., & Mueller, P. W. (2012). CFTR mutation anal-
ysis and haplotype associations in CF patients. Molec-
ular Genetics and Metabolism, 105, 249–254.
Giegling, I., Hartmann, A. M., Möller, H. J., & Rujescu,
D. (2006). Anger- and aggression-related traits are
associated with polymorphisms in the 5-HT-2A gene.
Journal of Affective Disorders, 96, 75–81.
4 Single Nucleotide Polymorphism (SNP)
Glusman, G., Caballero, J., Mauldin, D. E., Hood, L., &
Roach, J. C. (2011). Kaviar: An accessible system for
testing SNV novelty. Bioinformatics, 27, 3216–3217.
Ji, G., Long, Y., Zhou, Y., Huang, C., Gu, A., & Wang,
X. (2012). Common variants in mismatch repair genes
are associated with increased risk of sperm DNA dam-
age and male infertility. BMC Medicine, 10, 49.
Kimchi, S. C., Oh, J. M., Kim, I. W., Sauna, Z. E.,
Calcagno, A. M., Ambudkar, S. V., & Gottesman,
M. M. (2007). A silent polymorphism in the MDR1
gene changes substrate specificity. Science, 315,
525–528.
Kujovich, J. L. (2011). Factor V Leiden thrombophilia.
Genetics in Medicine, 13, 1–16.
Mohamed, A. A., Elsaid, O. M., Amer, E. A., Gerges, S. S.,
Saleh, M. A., El Abd, Y. S., Elosaily, H. H., Sleem,
M. I., & El Shimy, A. (2017). Clinical significance of
SNP (rs2596542) in histocompatibility complex class
I-related gene A promoter region among hepatitis
View publication stats
C virus related hepatocellular carcinoma cases. Journal
of Advanced Research, 8, 343–349.
Morita, A., Nakayama, T., Doba, N., Hinohara, S.,
Mizutani, T., & Soma, M. (2007). Genotyping of tri-
allelic SNPs using TaqMan PCR. Molecular and Cel-
lular Probes, 21, 171–176.
Singh, M., Singh, P., Juneja, P. K., Singh, S., & Kaur,
T. (2010). SNP–SNP interactions within APOE genes,
influencing the plasma lipids in postmenopausal osteo-
porosis. Rheumatology International, 31, 421–423.
Wei, Q., Wang, L., Wang, Q., Kruger, W. D., & Dunbrack,
R. L., Jr. (2010). Testing computational prediction of
missense mutation phenotypes: functional characteri-
zation of 204 mutations of human cystathionine beta
synthase. Proteins, 78, 2058–2074.
Wilkinson, D. G., Francis, P. T., Schwam, E., & Payne-
Parrish, J. (2004). Cholinesterase inhibitors used in the
treatment of alzheimer’s disease: the relationship
between pharmacological effects and clinical efficacy.
Drugs & Aging, 21, 453–478.