Prediction and evaluation of Deleterious Non-Synonymous SNPs (nsSNPs) in human IL17A Gene

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Research Paper 01/07/2021
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Prediction and evaluation of Deleterious Non-Synonymous SNPs (nsSNPs) in human IL17A Gene

Awad Ahmed Algarni
Int. J. Biosci.19( 1), 85-96, July 2021.
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Abstract

Single nucleotide polymorphisms in the IL17A gene are associated with many types of cancer. Therefore, the identification of functional and structural polymorphisms in IL17A is important to study and determine therapeutic targets and their potential impact. In this study, several computational methods have been used to identify non-synonymous SNPs that are deleterious in the IL17A gene, including SIFT, PolyPhen2, PROVEAN, SNAP. PhD-SNP, SNP&GO and Pmut were used to predict disease-associated nsSNPs. I-mutant and Mupro were used to predict protein stability. ConSurf was used to predict conserved residues and functional regions of the protein. Finally, SOPMA followed by Project Hope software was used to predict the effect of these mutations on protein structure and function. Our study concludes that ten nsSNPs (R69Q, A92S, C94S, R95C, C99F, D107G, V121I, V142M, T145I and P149L) were shown to be potentially deleterious in IL17A. The present study represents a comprehensive in silico analysis of the IL17A gene and will be a useful tool for future studies.

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Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. 2010. A method and server for predicting damaging missense mutations. Nature methods 7(4), 248-249. https://doi.org/10.1038/nmeth0410-248

Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, Fujita H, Nakamura M, Yoshioka D, Arima Y, Okubo M. 2008. The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. Journal of clinical immunology 28(1), 44-49. https://doi.org/10.1007/s10875-007-9125-8

Ashkenazy H, Erez E, Martz E, Pupko T, Ben-Tal N. 2010. ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic acids research 38, W529-W533. https://doi.org/10.1093/nar/gkq399

Barnes MR. 2010. Genetic variation analysis for biomedical researchers: a primer. Genetic Variation 1-20. https://doi.org/10.1007/978-1-60327-367-1_1

Bromberg Y, Overton J, Vaisse C, Leibel RL, Rost B. 2009. In silico mutagenesis: a case study of the melanocortin 4 receptor. The FASEB Journal 23(9), 3059-3069. https://doi.org/10.1096/fj.08-127530

Calabrese R, Capriotti E, Fariselli P, Martelli PL, Casadio R. 2009. Functional annotations improve the predictive score of human disease‐related mutations in proteins. Human mutation 30(8), 1237-1244. https://doi.org/10.1002/humu.21047

Capriotti E, Calabrese R, Casadio R. 2006. Predicting the insurgence of human genetic diseases associated to single point protein mutations with support vector machines and evolutionary information. Bioinformatics 22(22), 2729-2734. https://doi.org/10.1093/bioinformatics/btl423

Cheng S, Shao Z, Liu X, Guo L, Zhang X, Na Q, Chen X, Ma Y, Zheng J, Song B, Liu J. 2015. Interleukin 17A polymorphism elevates gene expression and is associated with increased risk of nonsmall cell lung cancer. DNA and cell biology 34(1), 63-68. https://doi.org/10.1089/dna.2014.2628

Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. 2012. Predicting the functional effect of amino acid substitutions and indels. PLoS One 7, e46688. https://doi.org/10.1371/journal.pone.0046688

Doniger SW, Kim HS, Swain D, Corcuera D, Williams M, Yang SP, Fay JC. 2008. A catalog of neutral and deleterious polymorphism in yeast. PLoS genetics 4(8), p.e1000183. https://doi.org/10.1371/journal.pgen.1000183

Duan Y, Shi JN, Pan C, Chen HL, Zhang SZ. 2014. Association between the interleukin-17A-197G> A (rs2275913) polymorphism and risk of digestive cancer. Asian Pacific Journal of Cancer Prevention 15(21), 9295-9300. https://doi.org/10.1007/s13277-014-1890-4

Ferrer-Costa C, Gelpí JL, Zamakola L, Parraga I, De La Cruz X, Orozco M. 2005. PMUT: a web-based tool for the annotation of pathological mutations on proteins. Bioinformatics 21(14), 3176-3178.  https://doi.org/10.1093/bioinformatics/bti486

Kim SW, Kim ES, Moon CM, Park JJ, Kim TI, Kim WH, Cheon JH. 2011. Genetic polymorphisms of IL-23R and IL-17A and novel insights into their associations with inflammatory bowel disease. Gut 60(11),1527-1536. https://doi.org/10.1136/gut.2011.238477

Kolls JK, Lindén A. 2004. Interleukin-17 family members and inflammation. Immunity 21(14), 467-476. https://doi.org/10.1016/j.immuni.2004.08.018

Kumar A. 2009. An overview of nested genes in eukaryotic genomes. Eukaryotic Cell 8(9), 1321-1329. https://doi.org/10.1128/EC.00143-09

Lv Q, Zhu D, Zhang J, Yi Y, Yang S, Zhang W. 2015. Association between six genetic variants of IL-17A and IL-17F and cervical cancer risk: a case–control study. Tumor Biology 36(5), 3979-3984. https://doi.org/10.1007/s13277-015-3041-y

Meng XY, Zhou CH, Ma J, Jiang C, Ji P. 2012. Expression of interleukin-17 and its clinical significance in gastric cancer patients. Medical oncology 29(5), 3024-3028. https://doi.org/10.1007/s12032-012-0273-1

Ng PC, Henikoff S. 2003. SIFT: Predicting amino acid changes that affect protein function. Nucleic acids research 31(13), 3812-3814. https://doi.org/10.1093/nar/gkg509

Nordang GB, Viken MK, Hollis-Moffatt JE, Merriman TR, Førre ØT, Helgetveit K, Kvien TK, Lie BA. 2009. Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patients from Norway and New Zealand. Rheumatology 48(4), 367-370. https://doi.org/10.1093/rheumatology/ken512

Omrane I, Marrakchi R, Baroudi O, Mezlini A, Ayari H, Medimegh I, Stambouli N, Kourda N, Bouzaienne H, Uhrhammer N, Bougatef K. 2014. Significant association between interleukin-17A polymorphism and colorectal cancer. Tumor Biology 35(7), 6627-6632. https://doi.org/10.1007/s13277-014-1890-4

Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. 2001. dbSNP: the NCBI database of genetic variation. Nucleic acids research 29(1), 308-311. https://doi.org/10.1093/nar/29.1.308

Sirisena ND, Samaranayake N, Dissanayake VH. 2019. Genotype data for single nucleotide polymorphism markers in sporadic breast cancer related genes in a Sri Lankan case–control cohort of postmenopausal women. BMC research notes 12(1), 1-3. https://doi.org/10.1186/s13104-019-4472-0

Thusberg J, Olatubosun A, Vihinen M. 2011. Performance of mutation pathogenicity prediction methods on missense variants. Human mutation 32(4), 358-368. https://doi.org/10.1002/humu.21445

Venselaar H, Te Beek TA, Kuipers RK, Hekkelman ML, Vriend G. 2010. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. BMC bioinformatics 11(1), 1-10. https://doi.org/10.1186/1471-2105-11-548

Wang L, Jiang Y, Zhang Y, Wang Y, Huang S, Wang Z, Tian B, Yang Y, Jiang W, Pang D. 2012. Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer. PloS one 7(3), p. e34400. https://doi.org/10.1371/journal.pone.0034400

Whiffin N, Ware JS, O’Donnell-Luria A. 2019. Improving the understanding of genetic variants in rare disease with large-scale reference populations. JAMA 322(13), 1305-1306. https://doi.org/10.1001/jama.2019.12891

Zhang X, Yu P, Wang Y, Jiang W, Shen F, Wang Y, Tu H, Yang X, Shi R, Zhang H. 2013. Genetic polymorphisms of interleukin 17A and interleukin 17F and their association with inflammatory bowel disease in a Chinese Han population. Inflammation Research 62(8), 743-750.  https://doi.org/10.1007/s00011-013-0629-9

Zhou B, Zhang P, Wang Y, Shi S, Zhang K, Liao H, Zhang L. 2013. Interleukin‐17 gene polymorphisms are associated with bladder cancer in a chinese han population. Molecular carcinogenesis 52(11), 871-878. https://doi.org/10.1002/mc.21928