Question 4 A user wishes to find all the single nucleotide polymorphisms that lie between two sequence-tagged sites. Do any of these single nucleotide polymorphisms fall within the coding region of a gene? Where can any additional information about the function of these genes be found?

AbstractCDKN1A also known as p21CIP1 /p21WAF1, a cyclin dependent kinase 1, interacts with proliferating cell nuclear antigen (PCNA) resulting in cell cycle inhibition in human. Non-synonymous single nucleotide polymorphisms (nsSNPs), which reside in the coding region of a gene, might distort the normal function of the corresponding protein. In silico analysis in this study followed many different algorithms. Following the final screening of 118 nsSNPs from dbSNP (NCBI), 12 missense SNPs (R19C (C→T), G23D (A→G), V25G (G→T), V25L (C→G), Q29P (A→C→G), F51L (C→T), E56K (A→G), T57I (C→T), G61R (C→G), G61D (A→G), Y151C (A→G) and R156W (C→G→T) were predicted to have deleterious effect by all the algorithms. Of them, R19C, G23D, F51L, Y151C and R156W occurred at the highly conserved site. G23D, F51L variants also occurred at the CDI domain. Homology structures of the protein predicted decrease of energy in mutant models. GV-GD scores predicted only two variants as neutral (V25L, F51L).

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In Silico Analysis of Nonsynonumus Single Nucleotide Polymorphisms(nsSNPs) in Human GAAGene

10.51527/v2i2.09 ◽

2021 ◽

pp. 78-92

Keyword(s):

Single Nucleotide Polymorphisms ◽

Pompe Disease ◽

Smooth Muscles ◽

Biological Information ◽

Nucleotide Polymorphisms ◽

Coding Region ◽

Single Nucleotide ◽

The Stability ◽

Alpha Glucosidase ◽

Gaa Gene

Background: Pompe disease an autosomal recessive lysosomal disorder caused by deficiency of acid alpha-glucosidase (GAA) gene, leading to a progressive accumulation of glycogen in lysosomes in skeletal, cardiac, and smooth muscles. GAA gene provides instructions for producing an enzyme called acid alpha-glucosidase. This enzyme is active in lysosomes, which are structures that serve as recycling centers within cells. Acid alpha-glucosidase normally breaks down glycogen into a simpler glucose. Glucose is the main energy source for most cells. Material and Methods: Information regarding GAA SNPs was obtained from National Center for Biological Information (NCBI) SNPs database, November 2020.The SNPs and the related ensembles proteins (ESNP) were obtained from the SNPs database and UniprotKB database. Analysis of Functional Consequences of coding nonsynonoumus single nucleotide polymorphisms (nsSNPs) by Sequence Homology Based Method wee done using SIFTS, Provean and Polyphen-2 software. Protein stability was predicted using I-Mutant and Mupro software. The pathogenicity and relation of the mutation to disease association was predicted by SNP&GO and PHD software. For the effect of the mutation on the protein structure and function, ProjectHope, Chimera and Raptor X were used. For the association, co-expression and shared domains of the gene to other genes GeneMANIA software was used. Results: GAA gene had254 SNPS WITH 179 SNPS IN CODING REGION AND 75 IN NON CODINGregion, nsSNPs were analyzed by SIFT software, and only 64 nsSNPs were predicted to be deleterious while 11 were tolerated. Using Provean software 53nsSNPs were deleterious and 11nsSNPs were neutral. These deleterious SNPs were analyzed using polyphen_2 software to predict the damaging SNPs, the damaging SNPs were 53 nsSNPs. Using I-mutant software for evaluation of the degree of stability due to mutation. The present study predicted 43 nsSNPsto decrease the stability of the protein, while only 10 SNPs had increased in the stability of the protein. For Mupro software52 nsSNPs decrease the stability of protein and only one SNP increase the stability of protein. For more confirmation for the mutation the study used PHD software in which 46nsSNPs were reported as a disease related, while 7SNPs were reported as neutral. SNP &GO software was also used, it predicted 37 SNPs as disease related, while 16 SNPs were reported as neutral. For ProjectHope the 20 damaging nsSNPs from previous software gave effect on the function and structure of the protein, Conclusion: The study concluded that there were 20 nsSNPs predicted to be damaging to the protein (rs1800307 rs18003122 rs28937909 rs61736895 rs121907937 rs121907938 rs121907945 rs139009731 rs142752477 rs144016984 rs147327209 rs148842275 rs202095215 rs369098202 rs372486238 rs372604133 rs374143224 rs374470794 rs374687883 rs377544304 ).These results may provide useful information needed to help researchers to use thesensSNPs as biomarkers for Pompe disease .

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