Volume 12, Issue 5 (Sep-Oct 2018)                   mljgoums 2018, 12(5): 29-33 | Back to browse issues page

XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Kheiri S, Safarzad M, Shariati M, Sohrabi H. Prioritization of Deleterious Variations in the Human Hypoxanthine-Guanine Phosphoribosyltransferase Gene. mljgoums. 2018; 12 (5) :29-33
URL: http://goums.ac.ir/mljgoums/article-1-1117-en.html
1- Department of Biotechnology, Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran, Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
2- Department of Biochemistry, Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran, Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
3- Department of Microbiology, Laboratory of Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
4- Department of Medical Biotechnology, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran , hsohrabi65@yahoo.com
Abstract:   (200 Views)
ABSTRACT
            Background and Objectives: Non-synonymous single nucleotide polymorphisms are typical genetic variations that may potentially affect the structure or function of expressed proteins, and therefore could be involved in complex disorders. A computational-based analysis has been done to evaluate the phenotypic effect of non-synonymous single nucleotide polymorphisms in the gene encoding the human hypoxanthine-guanine phosphoribosyltransferase (HGPRT-1). HGPRT-1 is an enzyme involved in purine recycling pathway and its deficiency is associated with several human genetic disorders.
            Methods: We provide a list of all amino acid replacements in the human HGPRT-1 from the dbSNP, Uniprot and dbEST databases. Sorting intolerant from tolerant (SIFT) and PolyPhen softwares were also used in our study.
            Results: Of 94 amino acid substitutions, rs 267606863 was predicted to be the most deleterious. Substitutions of S110L and S104A in flexible loop and D194N, D201Y, H204R, Y195C, F199V and H204D in hood domain were predicted as functionally damaging.
            Conclusion: It could be concluded that these intolerant changes may lie within a functional region of the protein and may affect the stability and folding of HGPRT-1. These variants could be used for future functional and molecular epidemiology studies of HGPRT-1-related disorders.
            Keywords: Polymorphism, Single Nucleotide, Amino acid substitution, Hypoxanthine Phosphoribosyltransferase.
Full-Text [PDF 536 kb]   (96 Downloads)    
Type of Study: Original Paper | Subject: Special
Received: 2018/08/13 | Accepted: 2018/08/13 | Published: 2018/08/13

References
1. Hladnik U, Nyhan WL, Bertelli M. Variable expression of HPRT deficiency in 5 members of a family with the same mutation. Archives of neurology. 2008; 65(9): 1240-3. doi: 10.1001/archneur.65.9.1240. [DOI:10.1001/archneur.65.9.1240]
2. Chandekar P, Madke B, Kar S, Yadav N. Lesch-nyhan syndrome in an Indian child. Indian journal of dermatology. 2015; 60(3): 298-300. doi: 10.4103/0019-5154.156392. [DOI:10.4103/0019-5154.156392]
3. Torres RJ, Puig JG. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet journal of rare diseases. 2007; 2 (1): 48. doi.org/10.1186/1750-1172-2-48 [DOI:10.1186/1750-1172-2-48]
4. Engle SJ, Womer DE, Davies PM, Boivin G, Sahota A, Simmonds HA, et al. HPRT-APRT-deficient mice are not a model for Lesch-Nyhan syndrome. Human molecular genetics. 1996; 5(10): 1607-10. [DOI:10.1093/hmg/5.10.1607]
5. Torres RJ, Prior C, Puig JG. Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency. Metabolism. 2007; 56(9): 1179-86. [DOI:10.1016/j.metabol.2007.04.013]
6. Wang L-L, Li Y, Zhou S-F. Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity. Toxicology letters. 2009; 187(2): 99-114. doi: 10.1016/j.toxlet.2009.02.007. [DOI:10.1016/j.toxlet.2009.02.007]
7. Bao L, Cui Y. Functional impacts of non-synonymous single nucleotide polymorphisms: Selective constraint and structural environments. FEBS letters. 2006; 580(5): 1231-4. DOI:10.1016/j.febslet.2006.01.035. [DOI:10.1016/j.febslet.2006.01.035]
8. Chasman D, Adams RM. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. Journal of molecular biology. 2001;307(2):683-706. DOI:10.1006/jmbi.2001.4510. [DOI:10.1006/jmbi.2001.4510]
9. Jordan DM, Ramensky VE, Sunyaev SR. Human allelic variation: perspective from protein function, structure, and evolution. Current opinion in structural biology. 2010; 20(3): 342-50. doi: 10.1016/j.sbi.2010.03.006. [DOI:10.1016/j.sbi.2010.03.006]
10. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. Journal of molecular biology. 1990; 215(3): 403-10. DOI:10.1016/S0022-2836(05)80360-2. [DOI:10.1016/S0022-2836(05)80360-2]
11. Gish W, States DJ. Identification of protein coding regions by database similarity search. Nature genetics. 1993; 3(3): 266-72. [DOI:10.1038/ng0393-266]
12. Boguski MS, Lowe TM, Tolstoshev CM. dbEST—database for "expressed sequence tags". Nature genetics. 1993; 4(4): 332-3. [DOI:10.1038/ng0893-332]
13. Ng PC, Henikoff S. SIFT: Predicting amino acid changes that affect protein function. Nucleic acids research. 2003; 31(13): 3812-4. [DOI:10.1093/nar/gkg509]
14. Ramensky V, Bork P, Sunyaev S. Human non‐synonymous SNPs: server and survey. Nucleic acids research. 2002; 30(17): 3894-900. [DOI:10.1093/nar/gkf493]
15. Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, et al. Genotype–phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain. 2014;137(5):1282-303. doi: 10.1093/brain/awt202. [DOI:10.1093/brain/awt202]
16. Monzani PS, Trapani S, Thiemann OH, Oliva G. Crystal structure of Leishmania tarentolae hypoxanthine-guanine phosphoribosyltransferase. BMC structural biology. 2007;7(1): 59. [DOI:10.1186/1472-6807-7-59]
17. Baba S, Saito T, Yamada Y, Takeshita E, Nomura N, Yamada K, et al. Novel mutation in HPRT1 causing a splicing error with multiple variations. Nucleosides, Nucleotides and Nucleic Acids. 2017; 36(1): 1-6. doi: 10.1080/15257770.2016.1163381. [DOI:10.1080/15257770.2016.1163381]
18. Thumfart J, Weschke B, Ringe H, Weinhold N, Müller D. Acute renal failure unmasking Lesch-Nyhan disease in a patient with tuberous sclerosis complex. European Journal of Paediatric Neurology. 2016; 20(4): 649-51. doi: 10.1016/j.ejpn.2016.04.014. [DOI:10.1016/j.ejpn.2016.04.014]
19. Keebaugh AC, Sullivan RT, Thomas JW, Program NCS. Gene duplication and inactivation in the HPRT gene family. Genomics. 2007; 89(1): 134-42. DOI:10.1016/j.ygeno.2006.07.003. [DOI:10.1016/j.ygeno.2006.07.003]
20. Flier JS, Moore MJ, Wilson JM, Young AB, Kelley WN. Hypoxanthine-guanine phosphoribosyltransferase deficiency: The molecular basis of the clinical syndromes. New England Journal of Medicine. 1983; 309(15): 900-10. [DOI:10.1056/NEJM198310133091507]
21. Duan J, Nilsson L, Lambert B. Structural and functional analysis of mutations at the human hypoxanthine phosphoribosyl transferase (HPRT1) locus. Human mutation. 2004; 23(6): 599-611. [DOI:10.1002/humu.20047]
22. Balendiran GK, Molina J, Xu Y, Torres‐Martinez J, Stevens R, Focia PJ, et al. Ternary complex structure of human HGPRTase, PRPP, Mg2+, and the inhibitor HPP reveals the involvement of the flexible loop in substrate binding. Protein Science. 1999; 8(5): 1023-31. DOI:10.1110/ps.8.5.1023. [DOI:10.1110/ps.8.5.1023]
23. Naderi M, Gharaei R, Soleymani-Nejadian E, Samadian E. In Silico survey of functional coding variants in human AEG-1 gene. Egyptian Journal of Medical Human Genetics. 2013;14(4):419-22. [DOI:10.1016/j.ejmhg.2013.08.002]

Add your comments about this article : Your username or Email:
CAPTCHA code

Send email to the article author


© 2007 All Rights Reserved | Medical Laboratory Journal