Volume 17, Issue 2 (Pajouhan Scientific Journal, Winter 2019)                   psj 2019, 17(2): 37-44 | Back to browse issues page


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Naddaf H, Sattari A, Mirzaahmadi S. Next Generation Sequencing a Method for Identifying Genetic Mutations Associated with Spina Bifida Disorder . psj. 2019; 17 (2) :37-44
URL: http://psj.umsha.ac.ir/article-1-467-en.html
1- Master of Genetic, College of Basic Science, Islamic Azad University, Zanjan Unit, Zanjan, Iran , haniehnaddaf@gmail.com
2- Post Doc of Medical Genetic, Assistant Professor, College of Basic Science, Islamic Azad University, Gorgan Unit, Gorgan, Iran
3- PhD of Molecular Genetic, Assistant Professor, College of Basic Science, Islamic Azad University, Zanjan unit, Zanjan, Iran
Abstract:   (1759 Views)
Background and Objective: Spina Bifida (SB) is a congenital malformation and is a result of the failure of the closure and failure of the neural tube. The causes and mechanisms of genetic involvement involved in the onset of SB are still ambiguous. The present study addresses the genetic variation in SB disease using Next Generation Sequencing (NGS) as a powerful molecular tool for comprehensive genetic disorders studies.
Materials and Methods: Three complete blood samples from people with spina bifida were investigated after DNA extraction using NGS-whole exome sequencing (NGS-WES) method and after comparing the obtained data with the control sample. The results were analyzed using Alignment software (bwa), variant calling (gatk4) and Annotation (wannovar) with the version of the Hg19 genome.
Results: Out of 559087 mutations, there are 1205 mutations of the type INDELs and 557882 mutations associated with SNPs. This number of mutations was compared with control samples and patients with SB. Further studies ultimately identified the genes of PAX3, CUBN, MTHFR and PDGFRA as more effective genes in the disease.
Conclusion: The NGS is a powerful method for the genetic evaluation of patients with SB that can help detect genetic disorders in these patients. Gene mutations found have all occurred in genes that are associated with evolution in the nervous system during the fetal period. These mutations should be confirmed by valid molecular methods.
Full-Text [PDF 233 kb]   (448 Downloads)    
Type of Study: Research Article | Subject: Basic Sciences
Received: 2018/10/16 | Accepted: 2018/12/15

References
1. Au KS, Ashley-Koch A, Northrup H. Epidemiologic and genetic aspects of spina bifida and other neural tube defects. Dev Disabil Res Rev. 2010; 16(1): 6-15. [DOI]
2. Lei Y, Finnell RH. New Techniques for the Study of Neural Tube Defects. Adv Tech Biol Med. 2016; 4(1).
3. DeJong PM, Adams NS, Mann RJ, Polley JW, Girotto JA. Management of Lumbosacral Myelomeningocele. Eplasty. 2016; 16: ic51.
4. Detrait ER, George TM, Etchevers HC, Gilbert JR, Vekemans M, Speer MC. Human neural tube defects: developmental biology, epidemiology, and genetics. Neurotoxicol Teratol. 2005; 27(3): 515-524. [DOI]
5. Copp AJ, Adzick NS, Chitty LS, Fletcher JM, Holmbeck GN, Shaw GM. Spina bifida. Nat Rev Dis Primers. 2015;1: 15007.
6. Fletcher JM, Brei TJ. Introduction: Spina bifida--a multidisciplinary perspective. Dev Disabil Res Rev. 2010; 16(1):1-5. [DOI]
7. Waller DK, Shaw GM, Rasmussen SA, Hobbs CA, Canfield MA, Siega-Riz AM, Gallaway MS, Correa A. Prepregnancy obesity as a risk factor for structural birth defects. Arch Pediatr Adolesc Med. 2007; 161(8): 745-750.
8. Vieira AR, Castillo Taucher S. Maternal age and neural tube defects: evidence for a greater effect in spina bifida than in anencephaly. Rev Med Chil. 2005; 133(1): 62-70.
9. Kirke PN, Molloy AM, Daly LE, Burke H, Weir DG, Scott JM. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med. 1993; 86(11): 703-708.
10. Molloy AM, Kirke PN, Troendle JF, Burke H, Sutton M, Brody LC, Scott JM, Mills JL. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic Acid fortification. Pediatrics. 2009; 123(3):917-923. [DOI]
11. Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LY. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. 2001; 285(23):2981-2986.
12. Lumley J, Watson L, Watson M, Bower C. Withdrawn: Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database Syst Rev. 2011(4): CD001056.
13. Scott JM, Weir DG, Molloy A, McPartlin J, Daly L, Kirke P. Folic acid metabolism and mechanisms of neural tube defects. Ciba Found Symp. 1994; 181: 180-187; discussion 187-191.
14. Harris MJ, Juriloff DM. An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure. Birth Defects Res A Clin Mol Teratol. 2010; 88(8):653-669. [DOI]
15. Kennedy D, Chitayat D, Winsor EJ, Silver M, Toi A. Prenatally diagnosed neural tube defects: ultrasound, chromosome, and autopsy or postnatal findings in 212 cases. Am J Med Genet. 1998; 77(4): 317-321.
16. Goetzinger KR, Stamilio DM, Dicke JM, Macones GA, Odibo AO. Evaluating the incidence and likelihood ratios for chromosomal abnormalities in fetuses with common central nervous system malformations. Am J Obstet Gynecol. 2008; 199(3):285 e1-6. [DOI]
17. Adzick NS. Prenatal diagnosis and treatment of spina bifida. Preface. Fetal Diagn Ther. 2015; 37(3):165.
18. Bevilacqua NS, Pedreira DA. Fetoscopy for meningo-myelocele repair: past, present and future. Einstein (Sao Paulo). 2015; 13(2):283-9. [DOI]
19. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010; 42(1):30-35. [DOI]
20. Warr A, Robert C, Hume D, Archibald A, Deeb N, Watson M. Exome Sequencing: Current and Future Perspectives. G3 (Bethesda). 2015; 5(8):1543-1550. [DOI]
21. Lohmann K, Klein C. Next generation sequencing and the future of genetic diagnosis. Neurotherapeutics. 2014; 11(4):699-707. [DOI]
22. Boudjadi S, Chatterjee B, Sun W, Vemu P, Barr FG. The expression and function of PAX3 in development and disease. Gene. 2018; 666:145-157. [DOI]
23. Stuart ET, Kioussi C, Gruss P. Mammalian Pax genes. Annu Rev Genet. 1994; 28:219-236.
24. Scholl FA, Kamarashev J, Murmann OV, Geertsen R, Dummer R, Schafer BW.PAX3 is expressed in human melanomas and contributes to tumor cell survival. Cancer Res. 2001; 61(3):823-6.
25. Christensen EI, Nielsen R, Birn H. From bowel to kidneys: the role of cubilin in physiology and disease. Nephrol Dial Transplant. 2013; 28(2):274-281. [DOI]
26. Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, de la Chapelle A, Moestrup SK, Ray R, Gliemann J, Willnow TE, Christensen EI. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). Proc Natl Acad Sci U S A. 200;. 98(24):13895-13900.
27. Fodinger M, Horl WH, Sunder-Plassmann G. Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol. 2000; 13(1):20-33.
28. Trimmer EE. Methylenetetrahydrofolate reductase: biochemical characterization and medical significance. Curr Pharm Des. 2013; 19(14):2574-2593.
29. Dean L. Methylenetetrahydrofolate Reductase Deficiency, in Medical Genetics Summarie. Pratt V, McLeod H, Rubinstein W, Dean L, Kattman B, Malheiro A ,Editors. 2012; Bethesda (MD).
30. Toepoel M, Steegers-Theunissen RP, Ouborg NJ, Franke B, Gonzalez-Zuloeta Ladd AM, Joosten PH, van Zoelen EJ. Interaction of PDGFRA promoter haplotypes and maternal environmental exposures in the risk of spina bifida. Birth Defects Res A Clin Mol Teratol. 2009; 85(7):629-236.
31. Qian C, Wong CWY, Wu Z, He Q, Xia H, Tam PKH, Wong KKY, Lui VCH. Stage specific requirement of platelet-derived growth factor receptor-alpha in embryonic development. PLoS One. 2017; 12(9):e0184473. [DOI]
32. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003; 299(5607):708-710.
33. Lu W, Zhu H, Wen S, Laurent C, Shaw GM, Lammer EJ, Finnell RH. Screening for novel PAX3 polymorphisms and risks of spina bifida. Birth Defects Res A Clin Mol Teratol. 2007; 79(1):45-49.
34. Agopian AJ, Bhalla AD, Boerwinkle E, Finnell RH, Grove ML, Hixson JE, Shimmin LC, Sewda A, Stuart C, Zhong Y, Zhu H ,Mitchell LE. Exon sequencing of PAX3 and T (brachyury) in cases with spina bifida. Birth Defects Res A Clin Mol Teratol. 2013; 97(9):597-601. [DOI]
35. Shaw GM, Lu W, Zhu H, Yang W, Briggs FB, Carmichael SL, Barcellos LF, Lammer EJ, Finnell RH. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects. BMC Med Genet. 2009; 10: 49. [DOI]
36. Greene ND, Stanier P, Copp AJ. Genetics of human neural tube defects. Hum Mol Genet. 2009; 18(R2):R113-29. [DOI]
37. Bassuk AG, Muthuswamy LB, Boland R, Smith TL, Hulstrand AM, Northrup H, Hakeman M, Dierdorff JM, Yung CK, Long A, Brouillette RB, Au KS, Gurnett C, Houston DW, Cornell RA, Manak JR. Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene. Hum Mol Genet. 2013; 22(6):1097-1111. [DOI]

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