Identificación de nuevos polimorfismos del Síndrome de Marfan, un estudio de caso
datacite.rights | http://purl.org/coar/access_right/c_16ec | spa |
dc.contributor.author | Rondón Payares, Karin Patricia | |
dc.date.accessioned | 2021-02-19T20:51:13Z | |
dc.date.available | 2021-02-19T20:51:13Z | |
dc.date.issued | 2020 | |
dc.description.abstract | Antecedentes: El síndrome de Marfan (SMF) es un trastorno autosómico dominante, causado por mutaciones del gen que codifica la fibrilina‐1, es un componente de glucoproteína de las fibras elásticas que tiene importantes funciones estructurales y reguladoras en la matriz extracelular, lo que lleva a una desregulación de la señalización del factor de crecimiento ‐ beta transformante (TGF‐β), que afecta los sistemas esquelético, ocular y cardiovascular, del tejido conectivo. Estos pacientes afectados llevan una esperanza de vida reducida, en gran medida dependiente de complicaciones cardiovasculares. Su buen pronóstico dependerá de un eficiente diagnóstico, tratamiento y el conocimiento del paciente de su enfermedad. Objetivos: Identificar los polimorfismos que influyen en la expresión del fenotipo y calidad de vida de un individuo con Síndrome de Marfan. Materiales y Métodos: Para ello tomamos el resultado del estudio molecular realizado por el paciente, mediante el método de secuenciación Sanger, el cual fue procesado y sus características de rendimiento fueron determinadas por el Laboratorio de Diagnóstico Cardiovascular Jhon Welsh (Baylor College of Medicine (BCM) Houston, Texas). Este laboratorio está certificado bajo las enmiendas de mejora del laboratorio clínico de 1988 (CLIA-88), que permitió conseguir las secuencias del resultado del estudio. A los resultados de la secuenciación se les realizó un análisis bioinformático para relacionar los polimorfismos encontrados en el paciente con el Síndrome de Marfan, por medio de herramientas como: El modelamiento por homología que consiste en alinear la secuencia de aminoácidos de la proteína con secuencias de proteínas de las cuales ya se conoce su estructura, partiendo de observaciones donde proteínas con funciones similares tienen estructuras similares (proteínas homologas), se usan estas proteínas de las cuales ya se conoce su estructura para plegar la proteína problema, las proteínas usadas como plantillas son obtenidas de la base de datos públicas como PDB. En algunos casos la proteína problema presenta mutaciones que son de nuestro interés y precisan ser estudiadas y analizadas, para ello se realizaron pasos adicionales en el modelamiento de la proteína para añadirle estas mutaciones y así verificar como estas afecta a la proteína en sí. Estas mutaciones previamente identificadas con técnicas como secuenciación y alineamiento fueron luego reproducidas en nuestra estructura tridimensional. | spa |
dc.description.abstract | Background: Marfan syndrome (MFS) is an autosomal dominant disorder, caused by mutations in the gene encoding fibrillin-1, it is a glycoprotein component of elastic fibers that has important structural and regulatory functions in the extracellular matrix, which leads to dysregulation of transforming growth factor-beta (TGF-β) signaling, which affects the skeletal, ocular, and cardiovascular systems of connective tissue. These affected patients have a shortened life expectancy, largely dependent on cardiovascular complications. Its good prognosis will depend on an efficient diagnosis, treatment and the knowledge of the patient of his disease. Objectives: To identify the polymorphisms that influence the expression of the phenotype and quality of life of an individual with Marfan Syndrome. Materials and Methods: For this we take the result of the molecular study carried out by the patient, using the Sanger sequencing method, which was processed and its performance characteristics were determined by the Jhon Welsh Cardiovascular Diagnostic Laboratory (Baylor College of Medicine (BCM) Houston Texas). This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), which allowed the sequences of the study result to be achieved. The results of the sequencing were subjected to a bioinformatic analysis to relate the polymorphisms found in the patient with Marfan Syndrome, using tools such as: Homology modeling, which consists of aligning the amino acid sequence of the protein with sequences of proteins whose structure is already known, based on observations where proteins with similar functions have similar structures (homologous proteins), these proteins are used whose structure is already known to fold the problem protein, the proteins used as templates are Obtained from the public database as PDB. In some cases, the problem protein presents mutations that are of our interest and need to be studied and analyzed, for this, additional steps were carried out in the modeling of the protein to add these mutations and thus verify how they affect the protein itself. These mutations previously identified with techniques such as sequencing and alignment were then reproduced in our three-dimensional structure. | eng |
dc.format.mimetype | spa | |
dc.identifier.uri | https://hdl.handle.net/20.500.12442/7096 | |
dc.language.iso | spa | spa |
dc.publisher | Ediciones Universidad Simón Bolívar | spa |
dc.publisher | Facultad de Ciencias Básicas y Biomédicas | spa |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | eng |
dc.rights.accessrights | info:eu-repo/semantics/restrictedAccess | spa |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Codón de parada | spa |
dc.subject | Fibrilina | spa |
dc.subject | Nosología de Ghent | spa |
dc.subject | Síndrome de Marfan | spa |
dc.subject | Análisis bioinformático | spa |
dc.subject | Stop codon | eng |
dc.subject | Fibrillin | eng |
dc.subject | Ghent nosology | eng |
dc.subject | Marfan syndrome | eng |
dc.subject | Bioinformatic analysis | eng |
dc.title | Identificación de nuevos polimorfismos del Síndrome de Marfan, un estudio de caso | spa |
dc.type.driver | info:eu-repo/semantics/masterThesis | spa |
dc.type.spa | Trabajo de grado máster | spa |
dcterms.references | Haine E, Salles JP, Khau Van Kien P, Conte-Auriol F, Gennero I, Plancke A, et al. Muscle and Bone Impairment in Children with Marfan Syndrome: Correlation with Age and FBN1 Genotype. J Bone Miner Res. 2015;30(8):1369–76. | eng |
dcterms.references | Jondeau G, Michel JB, Boileau C. The translational science of Marfan syndrome. Heart. 2011;97(15):1206–14. | eng |
dcterms.references | Verstraeten A, Alaerts M, Van Laer L, Loeys B. Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery. Hum Mutat. 2016;37(6):524–31. | eng |
dcterms.references | Loja Oropeza D, Vilca M, Avilés R, Necochea Y, Manrique M, Postigo R. Síndrome de Marfan. A Propósito de un Caso. An la Fac Med. 2014;62(1):56. | spa |
dcterms.references | Silverman DI, Burton KJ, Gray J, Bosner MS, Kouchoukos NT, Roman MJ, et al. Life expectancy in the Marfan syndrome. Am J Cardiol. 1995;75(2):157–60. | eng |
dcterms.references | Dietz H. Marfan Syndrome Summary. Adam MP, Ardinger HH, Pagon RA, al, Ed GeneReviews®. 2001;1–22. | eng |
dcterms.references | Nollen GJ, Mulder BJM. What is new in the Marfan syndrome? Int J Cardiol. 2004;97(SUPPL. 1):103–8. | eng |
dcterms.references | Barriales-Villa R, García-Giustiniani D, Monserrat L. Genética del síndrome de Marfan. Cardiocore. 2011;46(3):101–4. | spa |
dcterms.references | Dean JCS, Loeys B. Marfan syndrome and related disorders. Cardiovasc Genet Genomics Princ Clin Pract. 2018;589. | eng |
dcterms.references | Kayhan G, Ergun MA, Ergun SG, Kula S, Percin FE. Identification of Three Novel FBN1 Mutations and Their Phenotypic Relationship of Marfan Syndrome. Genet Test Mol Biomarkers. 2018;22(8):474–80. | eng |
dcterms.references | Kodolitsch Y Von, De Backer J, Schüler H, Bannas P, Behzadi C, Bernhardt AM, et al. Perspectives on the revised ghent criteria for the diagnosis of marfan syndrome. Appl Clin Genet. 2015;8:137–55. | eng |
dcterms.references | Cook JR, Ramirez F. Clinical, Diagnostic, and Therapeutic Aspects of the Marfan Syndrome. 2014;77–94. | eng |
dcterms.references | Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476–85. | eng |
dcterms.references | von Kodolitsch Y, Demolder A, Girdauskas E, Kaemmerer H, Kornhuber K, Muino Mosquera L, et al. Features of Marfan syndrome not listed in the Ghent nosology–the dark side of the disease. Expert Rev Cardiovasc Ther [Internet]. 2019;17(12):883–915. Available from: https://doi.org/10.1080/14779072.2019.1704625 | eng |
dcterms.references | Hofman KJ, Bernhardt BA, Pyeritz RE. Marfan syndrome: Neuropsychological aspects. Am J Med Genet. 1988;31(2):331–8. | eng |
dcterms.references | Achelrod D, Blankart CR, Linder R, Von Kodolitsch Y, Stargardt T. The economic impact of Marfan syndrome: A non-experimental, retrospective, population-based matched cohort study. Vol. 9, Orphanet Journal of Rare Diseases. 2014. | eng |
dcterms.references | Loeys B, Nuytinck L, Delvaux I, De Bie S, De Paepe A. Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome. Arch Intern Med. 2001;161(20):2447–54. | eng |
dcterms.references | Peters KF, Apse KA, Blackford A, McHugh B, Michalic D, Biesecker BB. Living with Marfan syndrome: Coping with stigma. Clin Genet. 2005;68(1):6–14. | eng |
dcterms.references | Dean JCS. Marfan syndrome: Clinical diagnosis and management. Eur J Hum Genet. 2007;15(7):724–33. | eng |
dcterms.references | Peters KF, Kong F, Hanslo M, Biesecker BB. Living with Marfan syndrome III. Quality of life and reproductive planning. Clin Genet. 2002;62(2):110–20. | eng |
dcterms.references | De Bie S, De Paepe A, Delvaux I, Davies S, Hennekam RCM. Marfan syndrome in Europe: A questionnaire study on patient perceptions. Community Genet. 2005;7(4):216–25. | eng |
dcterms.references | Fierro JAA, Aviña DAH. Síndrome con hábitos marfanoides. Rev Mex Pediatr. 2011;78(6):236–41. | spa |
dcterms.references | Giarelli E, Bernhardt BA, Pyeritz RE. Attitudes antecedent to transition to self-management of a chronic genetic disorder. Clin Genet. 2008;74(4):325–37. | eng |
dcterms.references | Lugo LE, Garcia HI, Gomez C. Confiabilidad del cuestionario de calidad de vida en salud SF-36 en Medellin, Colombia. Rev Fac Nac Salud Pública. 2006;24(2):37–50. | spa |
dcterms.references | Li X, Li Z, Zhou H, Gaynor SM, Liu Y, Chen H, et al. Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale. Nat Genet. 2020;52(9):969–83. | eng |
dcterms.references | Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: Methods for virtual ligand screening and profiling. Br J Pharmacol. 2007;152(1):9–20. | eng |
dcterms.references | Salmaso V, Moro S. Bridging molecular docking to molecular dynamics in exploring ligand-protein recognition process: An overview. Front Pharmacol. 2018;9(AUG):1–16. | eng |
dcterms.references | Hollingsworth SA, Dror RO. Molecular Dynamics Simulation for All. Neuron [Internet]. 2018;99(6):1129–43. Available from: https://doi.org/10.1016/j.neuron.2018.08.011 | eng |
dcterms.references | Bazzazi H, Isenberg JS, Popel AS. Inhibition of VEGFR2 activation and its downstream signaling to ERK1/2 and calcium by thrombospondin-1 (TSP1): In silico investigation. Front Physiol. 2017;8(FEB):1–12. | eng |
dcterms.references | Speed TJ, Mathur VA, Hand M, Christensen B, Sponseller PD, Williams KA, et al. Characterization of pain, disability, and psychological burden in Marfan syndrome. Am J Med Genet Part A. 2017;173(2):315–23. | eng |
dcterms.references | Sakai LY, Keene DR, Renard M, De Backer J. FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders. Gene [Internet]. 2016;592(1):279–91. Available from: http://dx.doi.org/10.1016/j.gene.2016.07.033 | eng |
dcterms.references | Arslan-Kirchner M, Arbustini E, Boileau C, Child A, Collod-Beroud G, De Paepe A, et al. Clinical utility gene card for: Marfan syndrome type 1 and related phenotypes [FBN1]. Vol. 18, European Journal of Human Genetics. 2010. p. 1070. | eng |
dcterms.references | Hubmacher D, Apte SS. ADAMTS proteins as modulators of microfibril formation and function. Matrix Biol [Internet]. 2015;47:34–43. Available from: http://dx.doi.org/10.1016/j.matbio.2015.05.004 | eng |
dcterms.references | Por DE. HUÉRFANAS-RARAS. | spa |
dcterms.references | Sneha P, Priya Doss CG. Molecular Dynamics: New Frontier in Personalized Medicine [Internet]. 1st ed. Vol. 102, Advances in Protein Chemistry and Structural Biology. Elsevier Inc.; 2016. 181–224 p. Available from: http://dx.doi.org/10.1016/bs.apcsb.2015.09.004 | eng |
dcterms.references | Reyes RV, Tirado Y, Valdiris V. Estudio y análisis comparativo de interacciones entre la proteina integrina con fragmentos de la proteína fibrilina-1 y fragmentos mutados de esta utilizando la metodología de docking molecular. Salud Uninorte. 2016;32(3):369–83. | spa |
dcterms.references | Floudas CA, Fung HK, McAllister SR, Mönnigmann M, Rajgaria R. Advances in protein structure prediction and de novo protein design: A review. Chem Eng Sci. 2006;61(3):966–88. | eng |
dcterms.references | Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics. 2008;9:1–8. | eng |
dcterms.references | Coelho SG, Almeida AG. Marfan syndrome revisited: From genetics to the clinic. Rev Port Cardiol [Internet]. 2020;39(4):215–26. Available from: https://doi.org/10.1016/j.repc.2019.09.008 | eng |
dcterms.references | Muñoz Sandoval J, Saldarriaga-Gil W, De Lourido CI. Síndrome de marfan, mutaciones nuevas y modificadoras del gen FBN1. Iatreia. 2014;27(2):206–15. | spa |
dcterms.references | Cãadas V, Vilacosta I, Bruna I, Fuster V. Marfan syndrome. Part 1: Pathophysiology and diagnosis. Nat Rev Cardiol [Internet]. 2010;7(5):256–65. Available from: http://dx.doi.org/10.1038/nrcardio.2010.30 | eng |
dcterms.references | Robinson PN, Godfrey M. The molecular genetics of Marfan syndrome and related microfibrillopathies. J Med Genet. 2000;37(1):9–25. | eng |
dcterms.references | Collod-Béroud G, Le Bourdelles S, Ades L, Ala-Kokko L, Booms P, Boxer M, et al. Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database. Hum Mutat. 2003;22(3):199–208. | eng |
dcterms.references | Hutchinson S, Furger A, Halliday D, Judge DP, Jefferson A, Dietz HC, et al. Allelic variation in normal human FBN1 expression in a family with Marfan syndrome: A potential modifier of phenotype? Hum Mol Genet. 2003;12(18):2269–76. | eng |
dcterms.references | Robertson IB, Dias HF, Osuch IH, Lowe ED, Jensen SA, Redfield C, et al. The N-Terminal Region of Fibrillin-1 Mediates a Bipartite Interaction with LTBP1. Structure [Internet]. 2017;25(8):1208-1221.e5. Available from: http://dx.doi.org/10.1016/j.str.2017.06.003 | eng |
dcterms.references | Thomson J, Singh M, Eckersley A, Cain SA, Sherratt MJ, Baldock C. Fibrillin microfibrils and elastic fibre proteins: Functional interactions and extracellular regulation of growth factors. Semin Cell Dev Biol [Internet]. 2019;89:109–17. Available from: https://doi.org/10.1016/j.semcdb.2018.07.016 | eng |
dcterms.references | Jensen SA, Robertson IB, Handford PA. Dissecting the fibrillin microfibril: Structural insights into organization and function. Structure [Internet]. 2012;20(2):215–25. Available from: http://dx.doi.org/10.1016/j.str.2011.12.008 | eng |
dcterms.references | Robinson PN, Godfrey M. The molecular genetics of Marfan syndrome and related microfibrillopathies. Vol. 37, Journal of Medical Genetics. 2000. p. 9–25. | eng |
dcterms.references | De Cario R, Sticchi E, Lucarini L, Attanasio M, Nistri S, Marcucci R, et al. Role of TGFBR1 and TGFBR2 genetic variants in Marfan syndrome. J Vasc Surg [Internet]. 2018;68(1):225-233.e5. Available from: https://doi.org/10.1016/j.jvs.2017.04.071 | eng |
dcterms.references | Loeys B, De Backer J, Van Acker P, Wettinck K, Pals G, Nuytinck L, et al. Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome. Hum Mutat. 2004;24(2):140–6. | eng |
dcterms.references | Pepe G, Giusti B, Evangelisti L, Mc P, Brunelli T, Giurlani L. in Marfan patients : genotype – phenotype correlation. 2001;1:444–50. | eng |
dcterms.references | Shih HY, Liu WS, Chen TJ. Neonatal Marfan syndrome - A case report. Acta Cardiol Sin. 2004;20(3):171–5. | eng |
dcterms.references | Dawson WM, Rhys GG, Woolfson DN. Towards functional de novo designed proteins. Curr Opin Chem Biol [Internet]. 2019;52:102–11. Available from: https://doi.org/10.1016/j.cbpa.2019.06.011 | eng |
dcterms.references | Morrison DA, Morgan MJ, Kelchner SA. Molecular homology and multiple-sequence alignment: An analysis of concepts and practice. Aust Syst Bot. 2015;28(1):46–62. | eng |
dcterms.references | Wells JN, Bergendahl LT, Marsh JA. Computational modelling of protein complex structure and assembly. Methods Mol Biol. 2018;1764:347–56. | eng |
dcterms.references | Singh P, Sharma P, Bisetty K, Perez JJ. Molecular dynamics simulations of Ac-3Aib-Cage-3Aib-NHMe. Mol Simul. 2010;36(13):1035–44. | eng |
dcterms.references | Chen J, Siu SWI. Machine learning approaches for quality assessment of protein structures. Biomolecules. 2020;10(4). | eng |
dcterms.references | Roy A, Kucukural A, Zhang Y. I-TASSER: A unified platform for automated protein structure and function prediction. Nat Protoc. 2010;5(4):725–38. | eng |
dcterms.references | Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y. The I-TASSER suite: Protein structure and function prediction. Nat Methods [Internet]. 2014;12(1):7–8. Available from: http://dx.doi.org/10.1038/nmeth.3213 | eng |
dcterms.references | Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res. 2018;46(W1):W296–303. | eng |
dcterms.references | Šali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. Vol. 234, Journal of Molecular Biology. 1993. p. 779–815. | eng |
dcterms.references | Song Y, Dimaio F, Wang RYR, Kim D, Miles C, Brunette T, et al. High-resolution comparative modeling with RosettaCM. Structure [Internet]. 2013;21(10):1735–42. Available from: http://dx.doi.org/10.1016/j.str.2013.08.005 | eng |
dcterms.references | Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera - A visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12. | eng |
dcterms.references | Damm KL, Carlson HA. Gaussian-weighted RMSD superposition of proteins: A structural comparison for flexible proteins and predicted protein structures. Biophys J [Internet]. 2006;90(12):4558–73. Available from: http://dx.doi.org/10.1529/biophysj.105.066654 | eng |
dcterms.references | Sneha P, Priya Doss CG. Molecular Dynamics: New Frontier in Personalized Medicine. Adv Protein Chem Struct Biol. 2016;102:181–224. | eng |
dcterms.references | Soto ME, Cano R, Criales CS, Avendaño L, Espínola N, García C. Pectus excavatum y carinatum en el síndrome de Marfan y síndromes similares: prevalencia e impacto clínico pulmonar y cardiovascular. Gac Med Mex. 2018;154(Suppl 2):S67–78. | spa |
dcterms.references | Enciclopedia Orphanet de la Discapacidad. El síndrome de Marfan. 2016;1–4. Available from: www.orpha.net/data/patho/Han/Int/es/Marfan_Es_es_HAN_ORPHA109.pdf | spa |
dcterms.references | Arn PH, Scherer LR, Haller JA, Pyeritiz RE. Outcome of pectus excavatum in patients with Marfan syndrome and in the general population. J Pediatr. 1989;115(6):954–8. | eng |
dcterms.references | Thacoor A. Mitral valve prolapse and Marfan syndrome. Congenit Heart Dis. 2017;12(4):430–4. | eng |
dcterms.references | Becerra-Muñoz VM, Gómez-Doblas JJ, Porras-Martín C, Such-Martínez M, Crespo-Leiro MG, Barriales-Villa R, et al. The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome. Orphanet J Rare Dis. 2018;13(1):1–9. | eng |
dcterms.references | Clínico C, Case C. SÍNDROME DE MARFÁN. 2016;34(1):65–75. | spa |
dcterms.references | Sheikhzadeh S, Kade C, Keyser B, Stuhrmann M, Arslan-Kirchner M, Rybczynski M, et al. Analysis of phenotype and genotype information for the diagnosis of Marfan syndrome. Clin Genet. 2012;82(3):240–7. | eng |
dcterms.references | Jensen SA, Handford PA. New insights into the structure, assembly and biological roles of 10-12 nm connective tissue microfibrils from fibrillin-1 studies. Biochem J. 2016;473(7):827–38. | eng |
dcterms.references | Case DA, Walker RC, Cheatham TE, Simmerling C, Roitberg A, Merz KM, et al. Amber 2018. Univ California, San Fr 2018 [Internet]. 2018;1–923. Available from: http://ambermd.org/doc12/Amber18.pdf | spa |
dcterms.references | Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser K, Simmerling C, et al. Subscriber access provided by UNIV OF MISSISSIPPI ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. Just Accept Manuscr • Publ Date [Internet]. 2015;7. Available from: http://pubs.acs.org | eng |
dcterms.references | Moon JR, Cho YA, Huh J, Kang IS, Kim DK. Structural equation modeling of the quality of life for patients with marfan syndrome. Health Qual Life Outcomes [Internet]. 2016;14(1):1–9. Available from: http://dx.doi.org/10.1186/s12955-016-0488-5 | eng |
dcterms.references | Rand-Hendriksen S, Johansen H, Semb SO, Geiran O, Stanghelle JK, Finset A. Health-related quality of life in Marfan syndrome: A cross-sectional study of Short Form 36 in 84 adults with a verified diagnosis. Genet Med. 2010;12(8):517–24. | eng |
dcterms.references | Moons P, De Volder E, Budts W, De Geest S, Elen J, Waeytens K, et al. What do adult patients with congenital heart disease know about their disease, treatment, and prevention of complications? A call for structured patient education. Heart. 2001;86(1):74–80. | eng |
dcterms.references | Vanegas-Flórez LM, Botero-Giraldo MÁ, Medina-Calero M, Carvajal-Tello N. Efectos del ejercicio físico en pacientes con síndrome de Marfán (revisión documental 2000-2016). Vol. 15, Duazary. 2018. p. 325. | spa |
oaire.version | info:eu-repo/semantics/acceptedVersion | spa |
sb.programa | Maestría en Genética | spa |
sb.sede | Sede Barranquilla | spa |