Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación
Las diferentes condiciones que experimenta Caretta caretta durante su ciclo de vida, dada su longevidad y capacidad de migrar grandes distancias, se refleja en cambios cualitativos y cuantitativos en la expresión de genes en las diferentes etapas de vida de la especie que pueden revelarse a través d...
- Autores:
- Tipo de recurso:
- Tesis
- Fecha de publicación:
- 2023
- Institución:
- Universidad de Bogotá Jorge Tadeo Lozano
- Repositorio:
- Expeditio: repositorio UTadeo
- Idioma:
- spa
- OAI Identifier:
- oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/31047
- Acceso en línea:
- http://hdl.handle.net/20.500.12010/31047
http://expeditio.utadeo.edu.co
- Palabra clave:
- Tortugas marinas -- Sangre -- Análisis -- Santa Marta (Magdalena, Colombia)
Tortugas marinas -- Especies -- Santa Marta (Magdalena, Colombia)
Caretta caretta -- Análisis
Caretta caretta -- Tesis y disertaciones académicas
Tortugas marinas -- Especies -- Tesis y disertaciones académicas
Marine turtles -- Reproductive aspects
Marine turtles -- Research
- Rights
- License
- Acceso restringido
| id |
UTADEO2_dbf63f8e6664672190c4ef941fb6d80a |
|---|---|
| oai_identifier_str |
oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/31047 |
| network_acronym_str |
UTADEO2 |
| network_name_str |
Expeditio: repositorio UTadeo |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación |
| dc.title.alternative.none.fl_str_mv |
In silico analysis and identification of genes expressed differentially between juveniles and adults of the loggerhead turtle (caretta caretta) related to hypoxia and inmune system: first approach |
| title |
Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación |
| spellingShingle |
Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación Tortugas marinas -- Sangre -- Análisis -- Santa Marta (Magdalena, Colombia) Tortugas marinas -- Especies -- Santa Marta (Magdalena, Colombia) Caretta caretta -- Análisis Caretta caretta -- Tesis y disertaciones académicas Tortugas marinas -- Especies -- Tesis y disertaciones académicas Marine turtles -- Reproductive aspects Marine turtles -- Research |
| title_short |
Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación |
| title_full |
Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación |
| title_fullStr |
Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación |
| title_full_unstemmed |
Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación |
| title_sort |
Análisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximación |
| dc.contributor.advisor.none.fl_str_mv |
Hernández Fernández, Javier Adolfo |
| dc.subject.spa.fl_str_mv |
Tortugas marinas -- Sangre -- Análisis -- Santa Marta (Magdalena, Colombia) Tortugas marinas -- Especies -- Santa Marta (Magdalena, Colombia) Caretta caretta -- Análisis |
| topic |
Tortugas marinas -- Sangre -- Análisis -- Santa Marta (Magdalena, Colombia) Tortugas marinas -- Especies -- Santa Marta (Magdalena, Colombia) Caretta caretta -- Análisis Caretta caretta -- Tesis y disertaciones académicas Tortugas marinas -- Especies -- Tesis y disertaciones académicas Marine turtles -- Reproductive aspects Marine turtles -- Research |
| dc.subject.lemb.spa.fl_str_mv |
Caretta caretta -- Tesis y disertaciones académicas Tortugas marinas -- Especies -- Tesis y disertaciones académicas |
| dc.subject.keyword.spa.fl_str_mv |
Marine turtles -- Reproductive aspects Marine turtles -- Research |
| description |
Las diferentes condiciones que experimenta Caretta caretta durante su ciclo de vida, dada su longevidad y capacidad de migrar grandes distancias, se refleja en cambios cualitativos y cuantitativos en la expresión de genes en las diferentes etapas de vida de la especie que pueden revelarse a través del análisis del transcriptoma. En este estudio se realizó un análisis de expresión diferencial de genes, comparando transcriptomas de tortugas adultas (Adul) y tortugas juveniles (Juv), y se relacionaron con hipoxia y respuesta inmune. Las secuencias usadas corresponden a tortugas en cautiverio anidantes del Caribe colombiano, disponibles en GenBank, las cuales se filtraron (Trimmomatic), alinearon, mapearon (HISAT2) y ensamblaron (StringTie) contra un transcriptoma de referencia. El nivel de expresión de las lecturas de cada transcriptoma se cuantificó (featureCounts) para el análisis de expresión diferencial (DESeq2) y los genes se anotaron funcionalmente (Blast2GO-OmicsBox). Se mapearon correctamente el 84 % de las lecturas, y de la comparación Adul versus Juv, se identificaron 1401 genes expresados diferencialmente (DEG) (p-aj < 0,05), 507 regulados al alza y 894 a la baja (log₂ fold-change). Se logró anotar funcionalmente el 40 % de los DEG, identificando 8252 términos GO y 583 rutas de referencia de la ontología KEGG, en dónde sobresale la respuesta inmunológica, la respuesta al estrés oxidativo, y el metabolismo de carbohidratos. Se proponen posibles mecanismos y rutas metabólicas implicadas con la expresión de estos genes, según su función y el nivel de expresión en cada estadío. Lo planteado en las hipótesis sugeridas debe ser sometido a investigación desde enfoques más específicos que consideren la medición de variables no evaluadas en la presente investigación. |
| publishDate |
2023 |
| dc.date.accessioned.none.fl_str_mv |
2023-03-08T20:23:05Z |
| dc.date.available.none.fl_str_mv |
2023-03-08T20:23:05Z |
| dc.date.created.none.fl_str_mv |
2023 |
| dc.type.local.spa.fl_str_mv |
Trabajo de grado de pregrado |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_46ec |
| format |
http://purl.org/coar/resource_type/c_46ec |
| dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/20.500.12010/31047 |
| dc.identifier.repourl.spa.fl_str_mv |
http://expeditio.utadeo.edu.co |
| url |
http://hdl.handle.net/20.500.12010/31047 http://expeditio.utadeo.edu.co |
| dc.language.iso.spa.fl_str_mv |
spa |
| language |
spa |
| dc.relation.references.spa.fl_str_mv |
Afgan, E., D. Baker, B. Batut, M. van den Beek, D. Bouvier, M. Čech, J. Chilton, D. Clements, N. Coraor, B. Grüning, A. Guerler, J. Hillman-Jackson, V. Jalili, H. Rasche, N. Soranzo, J. Goecks, J. Taylor, A. Nekrutenko and D. Blankenberg. 2018. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses. Nucleic Acids Research. 46(1,2): 537-544 p Agarwal A, D. Koppstein, J. Rozowsky, A. Sboner, L. Habegger, L.W. Hillier, R. Sasidharan, V. Reinke, R.H. Waterston and M. Gerstein. 2010. Comparison and calibration of transcriptome data from RNA-Seq and tiling arrays. BMC genomics. 11(1):1 p Alvarez, M., A.W. Schrey and C.L. Richards. 2015. Ten years of transcriptomics in wild populations: what have we learned about their ecology and evolution?. Mol Ecol. 24(4):710–25 p. Andrews, S. 2018. FastQC A Quality control tool for high throughput sequence data. Babraham. Bioinfo. http://www.bioinformatics.babraham.ac.uk/projects/fastqc. 7/04/2022. Banerjee, S.M., J.A. Stoll, C.D. Allen, J.M. Lynch, H.S. Harris, L. Kenyon, R.E. Connon, E.J. Sterling, E. Naro-Maciel, K. McFadden, M.M. Lamont, J. Benge, N.B. Fernandez, J.A. Seminoff, S.R. Benson, R.L. Lewison, T. Eguchi, T.M. Summers, J.R. Hapdei, M.R. Rice, S. Martin, T. Todd, P.H. Dutton, G.H. Balazs and L.M. Komoroske. 2021. Species and population specific gene expression in blood transcriptomes of marine turtles. BMC Genomics. 22: 346 p. Bentley, B.P., B.J. Haas, J.N. Tedeschi and O. Berry. 2017. Loggerhead Sea turtle embryos (Caretta caretta) regulate expression of stress response and developmental genes when exposed to a biologically realistic heat stress. Molecular ecology. 26(11): 2978-2992 p. Block, B.A., I.D. Jonsen, S.J. Jorgensen, A.J. Winship, S.A. Shaffer and S.J. Bograd. 2011. Tracking apex marine predator movements in a dynamic ocean. Nature. 475: 86–90 p. Bolger, A.M., M. Lohse and B. Usadel. 2014. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics. PubMed. 30: 2114–2120 p. Cásale, P. and A.D. Tucker. 2017. Caretta caretta (amended version of 2015 assessment). The IUCN Red List of Threatened Species 2017: e.T3897A119333622. https://dx.doi.org/10.2305/IUC N.UK.2017-2.RLTS.T3897A119333622.en. 21/12/2021. Canada's Genomic Enterprise. 2022. Loggerhead Sea Turtle (Caretta caretta) genome sequencing and assembly (Canada's Genomic Enterprise), rCarCar2. https://www.ncbi.nlm.ni h.gov/data-hub/genome/GCF_023653815.1/. 25/10/2022. Chamorro, C. 2019. Análisis de datos de RNA-Seq empleando diferentes paquetes desarrollados dentro del proyecto Bioconductor para estudios de expresión génica diferencial. Creative Commons. 74 p. Cocci, P., M. Capriotti, G. Mosconi and F.A. Palermo. 2017. Effects of endocrine disrupting chemicals on estrogen receptor alpha and heat shock protein 60 gene expression in primary cultures of loggerhead sea turtle (Caretta caretta) erythrocytes. Environmental Research. 158: 616-624 p Cocci, P., G. Mosconi, L. Bracchetti, J.M. Nalocca, E. Frapiccini, M. Marini, G. Caprioli, G. Sagratini and F.A. Palermo. 2018. Investigating the potential impact of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) on gene biomarker expression and global DNA methylation in loggerhead sea turtles (Caretta caretta) from the Adriatic Sea. Science of The Total Environment. 619–620: 49-57 p. Cocci, P., G. Mosconi and F.A. Palermo. 2022. Organic UV Filters Induce Toll-like-Receptors and Related Signaling Pathways in Peripheral Blood Mononuclear Cells of Juvenile Loggerhead Sea Turtles (Caretta caretta). Animals. 12(5): 594 p. Chow, J.C., N. Kyritsis, M. Mills, M.H. Godfrey, C.A. Harms, P.E. Anderson and A.M. Shedlock. 2021. Tissue and Temperature-Specific RNA-Seq Analysis Reveals Genomic Versatility and Adaptive Potential in Wild Sea Turtle Hatchlings (Caretta caretta). Animals. 11: 3013 p Chegwidden, WR. and N.D. Carter. 2000. Introduction to the carbonic anhydrases. EXS. 90: 13-28 p. Conesa, A., S. Götz, J.M. García-Gómez, J. Terol, M. Talón and M. Robles. 2005. Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research. Bioinformatics. 21(18): 3674-3676 p. Denley, A., E.R. Bonython, G.W. Booker, L.J. Cosgrove, B.E. Forbes, C.W. Ward and J.C. Wallace. 2004. Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. Molecular Endocrinology. 18(10): 2502– 2512 p. Dolmán, A.J. 1990. “The Potential Contribution of Marine Resources to Sustainable Development in Small-Island Developing Countries”, in Beller, W., P. D'Ayala and P. Hein, (Eds), Sustainable Development and Environmental Management of Small Islands. Man and the Biosphere Series. Volume 5. UNESCO, Paris, and Parthenon Publishing Carnforth. Eckert, K.L., K.A. Bjorndal, F.A. Abreu-Grobois y M. Donnelly. 2000. Técnicas de Investigación y Manejo para la Conservación de las Tortugas Marinas. Grupo especialista en Tortugas Marinas. Unión Internacional para la Conservación de la Naturaleza y Comisión de Supervivencia de Especies. 4: 270 p. Frasca, D., A.M. Landin, R.L. Riley and B.B. Blomberg. 2008. Mechanisms for decreased function of B cells in aged mice and humans. J. Immunol. 180: 2741–2746 p. Gardner, S.C., M.D. Pier, R. Wesselman and J.A. Juarez. 2003. Organochlorine contaminants in sea turtles from the eastern Pacific. Marine Pollution Bulletin. 46: 1082-1089 p. Grings, M., M. Wajner and G. Leipnitz. 2020. Mitochondrial dysfunction and redox homeostasis impairment as pathomechanisms of brain damage in ethylmalonic encephalopathy: insights from animal and human studies. Cellular and Molecular Neurobiology. 42: 1-11 p. Guillemot, F., A. Billault, O. Pourquie, G. Behar, A.M. Chaussé, R. Zoorob, G. Kreibich and C. Auffray. 1988. A molecular map of the chicken major histocompatibility complex: the class II beta genes are closely linked to the class I genes and the nucleolar organizer. The EMBO journal. 7(9): 2775- 2785 p. Gu, Y.Z., J.B. Hogenesch and C.A. Bradfield. 2000. The PAS Superfamily: Sensors of Environmental and Developmental Signals. Annu Rev Pharmacol. 40: 519–561 p. Harman, D. 1956. Aging: A theory based on free radical and radiation chemistry. Journal of Gerontology 11: 298–300 p Hawkes, L.A., A.C. Broderick, M.S. Coyne, M.H. Godfrey and B.J. Godley. 2007. Only some like it hot - quantifying the environmental niche of the loggerhead sea turtle. Divers. Distrib. 13: 447- 457 Heikkilä, M., A. Pasanen, K.I. Kivirikko and J. Myllyharju. 2011. Roles of the human hypoxia inducible factor (HIF)-3α variants in the hypoxia response. Life Sciences. 68(23): 3885–3901 Hernández-Fernández, J., A. Pinzón, L. and Mariño-Ramírez. 2017. De novo transcriptome assembly of loggerhead sea turtle nesting of the Colombian Caribbean. Genomics Data. 13: 18-20 p. Hernández-Fernández, J., A.M. Pinzón-Velasco, E.A. López-Barrera, M. Rodríguez-Becerra, J.L. Villanueva-Cañas, M. Alba, L. Mariño-Ramírez. 2021. De novo assembly and functional annotation of blood transcriptome of loggerhead turtle, and in silico characterization of peroxiredoxins and thioredoxins. PeerJ. 9: 32 p. Hochscheid, S., F. Bentivegna, M.N. Bradai and G.C. Hays. 2007a. Overwintering behaviour in sea turtles: dormancy is optional. Mar. Ecol. Prog. Ser. 340: 287-298 p. Hochscheid, S., C.R. McMahon, C.J.A. Bradshaw, F. Maffucci, F. Bentivegna and G.C. Hays. 2007b. Allometric scaling of lung volume and its consequences for marine turtle diving performance. Comp Biochem Physiol A. 148: 360–367 p. Hoekstra, L.A., T.S. Schwartz, A.M. Sparkman, D.A.W. Miller and A.M. Bronikowski. 2020. The untapped potential of reptile biodiversity for understanding how and why animals age. Funct Ecol. 34: 38– 54 p. Iverson, A.R., I. Fujisaki, M.M. Lamont and K.M. Hart. 2019. Loggerhead Sea turtle (Caretta caretta) diving changes with productivity, behavioral mode, and sea surface temperature. PloS one. 14(8): 19 p. Kamei, H. 2020. Oxygen and embryonic growth: the role of insulin-like growth factor signaling. General and Comparative Endocrinology. 294: 113473 p Keller, J.M., J.R. Kucklick, M.A. Stamper, C.A. Harms and P.D. McClellan-Green. 2004. Associations between organochlorine contaminant concentrations and clinical health parameters in loggerhead sea turtles from North Carolina, USA. Environ. Health Persp. 112: 1074-1079 p. Keller, J.M., P.D. McClellan-Green, A.M. Lee, M.D. Arendt, P.P. Maier, A.L. Segars, J.D. Whitaker, D.E. Keil and M.M. Peden-Adams. 2005. Mitogen-induced lymphocyte proliferation in loggerhead sea turtles: comparison of methods and effects of gender, plasma testosterone concentration, and body condition on immunity. Vet. Immunol. Immunopathol. 103: 269-281 p. Keller, J.M., P.D. McClellan-Green, J.R. Kucklick, D.E. Keil and M.M. Peden-Adams. 2006. Effects of organochlorine contaminants on loggerhead sea turtle immunity: comparison of a correlative field study and in vitro exposure experiments. Environ. Health. Persp. 114: 70-76 p. Kim, G. and R. Levine. 2005. Molecular determinants of S-glutathionylation of carbonic anhydrase 3. Antioxidants and Redox Signalling. 7: 849-854 p Kim, D., B. Langmead and S.L. Salzberg. 2015. HISAT: a fast spliced aligner with low memory requirements. Nature Methods. 12(4): 357-360 p. Krivoruchko, A. and K.B. Storey. 2015. Turtle anoxia tolerance: biochemistry and gene regulation. Biochimica et Biophysica Acta (BBA)-General Subjects. 1850(6): 1188-1196 p. Kovaka, S., A.V. Zimin, G.M. Pertea, R. Razaghi, S.L. Salzberg and M. Pertea. 2019. Transcriptome assembly from long-read RNA-seq alignments with StringTie2. Genome Biology. 20(1): 1-14 p. Ku, H.H., U.T. Brunk and R.S. Sohal. 1993. Relationship between mitochondrial superoxide and hydrogen‐peroxide production and longevity of mammalian‐species. Free Radical Biology and Medicine. 15: 621–627 p. Lambert, A.J., H.M. Boysen, J.A. Buckingham, T. Yang, A. Podlutsky, S.N. Austad and M.D. Marca. 2007. Low rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms. Aging Cell. 6: 607–618 p. Lapennas, G.N. and P.L. Lutz. 1982. Oxygen affinity of sea turtle blood. Respiration physiology. 48(1): 59-74 p. Lee, J.S., W.O. Ward, D.C. Wolf, J.W. Allen, C. Mills, M.J. DeVito and J.C. Corton. 2008. Coordinated Changes in Xenobiotic Metabolizing Enzyme Gene Expression in Aging Male Rats. Toxicological Sciences. 106(1): 263-283 p. Lin, K., J.B. Dorman, A. Rodan and C. Kenyon. 1997. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science. 278(5341): 1319- 1322 p. Li, G.X., Y. Hirabayashi, B.I. Yoon, Y. Kawasaki, I. Tsuboi, Y. Kodama, Y. Kurokawa, J. Yodoi, J. Kanno and T. Inoue. 2006. Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Exp Hematol. 34(12): 1687-1697 p. Li, C., L. Song, J. Zhao, L. Zhu, H. Zou, H. Zhang, H. Wang and Z. Cai. 2007. Preliminary study on a potential antibacterial peptide derived from histone H2A in hemocytes of scallop Chlamys farreri. Fish & Shellfish Immunology. 22(6): 663-672 p. Li, H., B. Handsaker, A. Wysoker, T. Fennell, J. Ruan, N. Homer, G. Marth, G. Abecasis and R. Durbin. 2009. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 25(16): 2078- 2079 p. Liao, Y., G.K. Smyth and W. Shi. 2014. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 30(7): 923-930 p. Love, M.I., W. Huber and S. Anderson. 2014. Moderated estimation of fold changes and dispersion of RNA-Seq data with DESeq. Genome Biol. 15(12): 550 p. Lutz, P.L. and T.B. Bentley. 1985. Respiratory Physiology of Diving in the Sea Turtle. Copeia. 1985(3): 671–679 p Lutcavage, M.E., P.G. Bushnell and D.R. Jones. 1990. Oxygen transport in the leatherback sea turtle Dermochelys coriacea. Physiol. Zool. 63: 1012-1024 p. Lukacs, M.F., H. Harstad, U. Grimholt, M. Beetz-Sargent, G.A. Cooper, L. Reid, H.G. Bakke, R.B. Phillips, K.M. Miller, W.S. Davidson and B.F. Koop. 2007. Genomic organization of duplicated major histocompatibility complex class I regions in Atlantic salmon (Salmo salar). BMC genomics. 8(1): 1-16 p. Marco, A., C. Carreras y E. Abella. 2008. Tortuga boba – Caretta caretta. En: Enciclopedia Virtual de los Vertebrados Españoles. Carrascal, L. M., Salvador, A. (Eds.). Museo Nacional de Ciencias Naturales, Madrid. http://www.vertebradosibericos.org/. Marzio, R., J. Mauël and S. Betz-Corradin. 1999. CD69 and Regulation of the Immune Function. Immunopharmacology and Immunotoxicology. 21(3): 565-582 p. Mayne, B., A.D. Tucker, O. Berry y S. Jarman. 2020. Lifespan estimation in marine turtles using genomic promoter CpG density. Plos one. 15(7): 1-8 p. McDermaid, A., B. Monier, J. Zhao, B. Liu and Q. Ma. 2019. Interpretation of differential gene expression results of RNA-seq data: review and integration. Briefings in bioinformatics. 20: 2044–2054 p. Metzker, M.L. 2010. Sequencing technologies - the next generation. Nature reviews Genetics. 11(1): 31-46 p. Milton, S.L. 1994. The physiology of hypoxia and anoxia tolerance in three species of turtle: the loggerhead sea turtle (Caretta caretta), green sea turtle (Chelonia mydas), and freshwater Trachemys scripta. University of Miami. 175 p. Mu, Y., W. Li, Z. Wei, L. He, W. Zhang and X. Chen. 2020. Transcriptome analysis reveals molecular strategies in gills and heart of large yellow croaker (Larimichthys crocea) under hypoxia stress. Fish & shellfish immunology. 104: 304-313 p. Nath, A.K., J. Ma, Z.Z. Chen, Z. Li, M.D.C. Vitery, M.L. Kelley, R.T. Peterson, R.E. Gerszten and J.J. Yeh. 2020. Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish. The FASEB Journal. 34(1): 1546-1557 p. Niu, N., D.J. Schaid, R.P Abo, K. Kalari, B.L. Fridley, Q. Feng, G. Jenkins, A. Batzler, A.G. Brisbin, J.M. Cunningham, L. Li, Z. Sun, P. Yang and L. Wang. 2012. Genetic association with overall survival of taxane-treated lung cancer patients -a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study. BMC cancer. 12(1): 1-13 p. Ogg, S., S. Paradis, S. Gottlieb, G.I. Patterson, L. Lee, H.A. Tissenbaum, and G. Ruvkun. 1997. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 389: 994-999 p Olson, K.R., J.A. Donald, R.A. Dombkowski and S.F. Perry. 2012. Evolutionary and comparative aspects of nitric oxide, carbon monoxide and hydrogen sulfide. Respiratory physiology & neurobiology. 184(2): 117-129 p. Ozsolak, F. and P.M. Milos. 2011. RNA sequencing: advances, challenges, and opportunities. Nature Rev. Genet. 12: 87–98 p. Pappworth, I.Y., C. Hayes, J. Dimmick, B.P. Morgan, V.M. Holers and K.J. Marchbank. 2012. Mice expressing human CR1/CD35 have an enhanced humoral immune response to T-dependent antigens but fail to correct the effect of premature human CR2 expression. Immunobiology. 217(2): 147-157 p. Potter, C. and A.L. Harris. 2004. Hypoxia inducible carbonic anhydrase IX, marker of tumor: hypoxia, survival pathway and therapy target. Cell cycle. 3(2): 159-162 p. Quesada, V., S. Freitas-Rodríguez, J. Miller, J.G. Pérez-Silva, Z.F. Jiang, W. Tapia and C. López-Otín. 2019. Giant tortoise genomes provide insights into longevity and age-related disease. Nature ecology & evolution. 3(1): 87-95 p. Raymond, W., N.A. Vo and A. Kiyoshi. 2012. Transformations for the compression of FASTQ quality scores of next-generation sequencing data. Bioinformatics. 28(5): 628–635 p. Ritchie, M.E., B. Phipson, D. Wu, Y. Hu, C.W Law y W. Shi. 2015. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic acids research. 43(7): 47 p. Robinson, M.D., D.J. McCarthy and G.K. Smith. 2010. EdgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 26(1): 40-139 p. Rousselet, E., M. Levin, E. Gebhard, B.M. Higgins, S. DeGuise and C.A. Godard-Codding. 2013. Evaluation of immune functions in captive immature loggerhead sea turtles (Caretta caretta). Veterinary Immunology and Immunopathology. 156(1-2): 43-53 p. Robin, J.D., A.T. Ludlow, R. LaRanger, W.E. Wright and J.W. Shay. 2016. Comparison of DNA quantification methods for next generation sequencing. Scientific reports. 6(1): 1-10 p. Sancho, D., M. Gómez and F. Sánchez-Madrid. 2005. CD69 is an immunoregulatory molecule induced following activation. Trends in immunology. 26(3): 136-140 p. Schmidt, E. and H. Knackmuss. 1980. Chemical structure and biodegradability of halogenated aromatic compounds. Conversion of chlorinated muconic acids into maleoylacetic acid. Biochemical Journal. 192(1): 339-347 p. Schwartz, T.S. and A.M. Bronikowski. 2016. Evolution and function of the insulin and insulin like signaling network in ectothermic reptiles: some answers and more questions. Integrative and Comparative Biology. 56(2): 171-184 p. Seim, I., X. Fang, Z. Xiong, A.V. Lobanov, Z. Huang, S. Ma and V.N. Gladyshev. 2013. Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii. Nature communications. 4(1): 1-8 p. Shiina, T., H. Inoko and J.K. Kulski. 2004. An update of the HLA genomic region, locus information and disease associations. Tissue Antigens. 64: 631-649 p. Silagi, E.S., P. Batista, I.M. Shapiro and M.V. Risbud. 2018. Expression of carbonic anhydrase III, a nucleus pulposus phenotypic marker, is hypoxia-responsive and confers protection from oxidative stress-induced cell death. Scientific Reports. 8(1): 1-13 p. Sparkman, A.M., T.S. Schwartz, J.A. Madden, S.E. Boyken, N.B. Ford, J.M. Serb and A.M. Bronikowski. 2012. Rates of molecular evolution vary in vertebrates for insulin-like growth factor-1 (IGF-1), a pleiotropic locus that regulates life history traits. General and comparative endocrinology. 178(1): 164-173 p. Speakman, J.R., J.D. Blount, A.M. Bronikowski, R. Buffenstein, C. Isaksson, T.B.L. Kirkwood and C. Selman. 2015. Oxidative stress and life histories: Unresolved issues and current needs. Ecology and Evolution. 5: S745–S757 p. Steinmann, G.G. 1986 Changes in the human thymus during aging. Curr. Top.. Pathol. 75: 43-Storey, K.B. 2007. Anoxia tolerance in turtles: Metabolic regulation and gene expression. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. 147(2): 263- 276 p. Stutte, S., T. Quast, N. Gerbitzki, T. Savinko, N. Novak, J. Reifenberger, B. Homey, W. Kolanus, H. Alenius and I. Forster. 2010. Requirement of CCL17 for CCR7- and CXCR4-dependent migration of cutaneous dendritic cells. Proceedings of the National Academy of Sciences. 107(19): 8736-8741 p. Supuran, C.T. 2016. Structure and function of carbonic anhydrases. Biochem. J. 473: 2023– 2032 p. Su, S., C.W. Law, C. Ah-Cann, M.L. Asselin-Labat, M.E. Blewitt and M.E. Ritchie. 2017. Glimma: interactive graphics for gene expression analysis. Bioinformatics. 33(13): 2050-2052 p. Thankaswamy-Kosalai, S., P. Sen and I. Nookaew. 2017. Evaluation and assessment of read mapping by multiple next-generation sequencing aligners based on genome-wide characteristics. Genomics. 109(3-4): 186-191 p. Tenney, S.M., D. Bartlett, J.P Farber and J.E. Remmers. 1974. Mechanics of the respiratory cycle in the green turtle (Chelonia mydas). Respiration physiology. 22(3): 361-368 p Teelucksingh, S., S. Eckert and P. Nunes. 2010. Marine turtles, ecosystem services and human welfare in the marine ecosystems of the Caribbean Sea: a discussion of key methodologies. Études caribéennes. 15: 2–14 p. Ujvari, B. and T. Madsen. 2011. Do natural antibodies compensate for humoral immunosenescence in tropical pythons?. Funct. Ecol. 25: 813–817 p. van Dam R.P. and C.E. Diez. 1997. Diving behavior of immature hawksbills (Eretmochelys imbricata) in a Caribbean reef habitat. Coral Reefs. 16:133–138 p. Wang, Z., M. Gerstein and M. Snyder. 2009. RNA-seq: a revolutionary tool for transcriptomics. Nature Rev. Genet. 10: 57–63 p. Wu, D. and S.N. Meydani. 2008. Age‐associated changes in immune and inflammatory responses: impact of vitamin E intervention. Journal of leukocyte biology. 84(4): 900-914 p. Wykoff, C.C., N.J. Beasley, P.H. Watson, K.J. Turner, J. Pastorek, A. Sibtain, G.D. Wilson, H. Turley, K.L. Talks, P.H. Maxwell, C.W. Pugh, P.J. Ratcliffe and AL. Harris. 2000. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res. 60:7075–7083 p. Yu, Y., J.C. Fuscoe, C. Zhao, C. Guo, M. Jia, T. Qing, D.I. Bannon, L. Lancashire, W. Bao, T. Du, H. Luo, Z. Su, W.D. Jones, C.L. Moland, W.S. Branham, F. Qian, B. Ning, Y. Li, H. Hong, L. Guo, N. Mei, T. Shi, K.Y. Wang, R.D. Wolfinger and C. Wang. 2014. A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nature communications. 5(1): 1-11 p. Zhang, G., J. Zhang, X. Wen, C. Zhao, H. Zhang, X. Li and S. Yin. 2017. Comparative iTRAQ‐ Based Quantitative Proteomic Analysis of Pelteobagrus vachelli Liver under Acute Hypoxia: Implications in Metabolic Responses. Proteomics. 17: 17-18 p. Zimmerman, L.M., G.S. Clairardin, R.T. Paitz, J.W. Hicke, K.A. LaMagdeleine, L.A. Vogel and R.M. Bowden. 2013. Humoral immune responses are maintained with age in a long-lived ectotherm, the red-eared slider turtle. Journal of Experimental Biology. 216(4): 633-640 p Zmienko, A., P. Jackowiak and M. Figlerowicz. 2011. Transcriptome sequencing: next generation approach to RNA functional analysis. BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology. 92(4): 311-319 p |
| dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_f1cf |
| dc.rights.local.spa.fl_str_mv |
Acceso restringido |
| rights_invalid_str_mv |
Acceso restringido http://purl.org/coar/access_right/c_f1cf |
| dc.format.extent.spa.fl_str_mv |
31 páginas |
| dc.format.mimetype.spa.fl_str_mv |
application/pdf |
| dc.format.rda.spa.fl_str_mv |
1 recurso en línea (archivo de texto) |
| dc.coverage.spatial.spa.fl_str_mv |
Colombia |
| dc.publisher.spa.fl_str_mv |
Universidad de Bogotá Jorge Tadeo Lozano |
| dc.publisher.program.spa.fl_str_mv |
Biología marina |
| dc.publisher.faculty.spa.fl_str_mv |
Facultad de Ciencias Naturales e Ingeniería |
| dc.source.spa.fl_str_mv |
Universidad de Bogotá Jorge Tadeo Lozano Expeditio Repositorio Institucional UJTL |
| institution |
Universidad de Bogotá Jorge Tadeo Lozano |
| bitstream.url.fl_str_mv |
https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/31047/6/Rivera-Forero%20Catalina%20Tesis_2023.pdf.jpg https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/31047/2/license.txt https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/31047/4/Permiso%20de%20publicaci%c3%b3n%20tesis.pdf https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/31047/7/Rivera-Forero%20Catalina%20Tesis_2023.pdf |
| bitstream.checksum.fl_str_mv |
521bcfe28949358f545edb9133bbbdc7 baba314677a6b940f072575a13bb6906 634efe5537aa3296497da87b3b00e62f 41c6743359c96c37efc0d2c7f4921879 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio Institucional - Universidad Jorge Tadeo Lozano |
| repository.mail.fl_str_mv |
expeditiorepositorio@utadeo.edu.co |
| _version_ |
1814213789999955968 |
| spelling |
EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DE BOGOTA JORGE TADEO LOZANO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DE BOGOTÁ JORGE TADEO LOZANO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. Para el correcto ejercicio de mi derecho de habeas data cuento con la cuenta de correo protecciondatos@utadeo.edu.co, donde previa identificación podré solicitar la consulta, corrección y supresión de mis datosAcceso restringidohttp://purl.org/coar/access_right/c_f1cfHernández Fernández, Javier AdolfoRivera Forero, CatalinaBiólogo(s) marinoColombia2023-03-08T20:23:05Z2023-03-08T20:23:05Z2023http://hdl.handle.net/20.500.12010/31047http://expeditio.utadeo.edu.coLas diferentes condiciones que experimenta Caretta caretta durante su ciclo de vida, dada su longevidad y capacidad de migrar grandes distancias, se refleja en cambios cualitativos y cuantitativos en la expresión de genes en las diferentes etapas de vida de la especie que pueden revelarse a través del análisis del transcriptoma. En este estudio se realizó un análisis de expresión diferencial de genes, comparando transcriptomas de tortugas adultas (Adul) y tortugas juveniles (Juv), y se relacionaron con hipoxia y respuesta inmune. Las secuencias usadas corresponden a tortugas en cautiverio anidantes del Caribe colombiano, disponibles en GenBank, las cuales se filtraron (Trimmomatic), alinearon, mapearon (HISAT2) y ensamblaron (StringTie) contra un transcriptoma de referencia. El nivel de expresión de las lecturas de cada transcriptoma se cuantificó (featureCounts) para el análisis de expresión diferencial (DESeq2) y los genes se anotaron funcionalmente (Blast2GO-OmicsBox). Se mapearon correctamente el 84 % de las lecturas, y de la comparación Adul versus Juv, se identificaron 1401 genes expresados diferencialmente (DEG) (p-aj < 0,05), 507 regulados al alza y 894 a la baja (log₂ fold-change). Se logró anotar funcionalmente el 40 % de los DEG, identificando 8252 términos GO y 583 rutas de referencia de la ontología KEGG, en dónde sobresale la respuesta inmunológica, la respuesta al estrés oxidativo, y el metabolismo de carbohidratos. Se proponen posibles mecanismos y rutas metabólicas implicadas con la expresión de estos genes, según su función y el nivel de expresión en cada estadío. Lo planteado en las hipótesis sugeridas debe ser sometido a investigación desde enfoques más específicos que consideren la medición de variables no evaluadas en la presente investigación.#BiologíaMarinaRequerimientos de sistema: Adobe Acrobat ReaderThe different conditions experienced by Caretta caretta during their life cycle, due to its longevity and the ability to migrate long distances, are reflected in qualitative and quantitative changes in gene expression at different life stages of the species that can be revealed through transcriptome analysis. In this study, a differential gene expression analysis was performed, comparing transcriptomes of adult turtles (Adul) and juvenile turtles (Juv), and related to hypoxia and immune response. The sequences used correspond to captive nesting turtles from the Colombian Caribbean, available in GenBank, these sequences were filtered (Trimmomatic), aligned, mapped (HISAT2) and assembled (StringTie) against a reference transcriptome. The expression level of reads from each transcriptome were quantified (featureCounts) for differential expression analysis (DESeq2) and genes were functionally annotated (Blast2GO-OmicsBox). 84% of reads were correctly mapped, and from the Adul versus Juv comparison, 1401 differentially expressed genes (DEGs) were identified (p-aj < 0.05), 507 up-regulated and 894 down-regulated (log₂ fold-change). 40 % of the DEGs were functionally annotated, identifying 8252 GO terms and 583 reference pathways of the KEGG ontology, where the immune response, oxidative stress response, and carbohydrate metabolism stand out. Possible mechanisms and metabolic pathways involved with the expression of these genes are proposed, according to their function and level of expression in each stage. The suggested hypotheses should be subjected to research from more specific approaches that consider the measurement of variables not evaluated in the present investigation.31 páginasapplication/pdf1 recurso en línea (archivo de texto)spaUniversidad de Bogotá Jorge Tadeo LozanoBiología marinaFacultad de Ciencias Naturales e IngenieríaUniversidad de Bogotá Jorge Tadeo LozanoExpeditio Repositorio Institucional UJTLTortugas marinas -- Sangre -- Análisis -- Santa Marta (Magdalena, Colombia)Tortugas marinas -- Especies -- Santa Marta (Magdalena, Colombia)Caretta caretta -- AnálisisCaretta caretta -- Tesis y disertaciones académicasTortugas marinas -- Especies -- Tesis y disertaciones académicasMarine turtles -- Reproductive aspectsMarine turtles -- ResearchAnálisis e identificación in silico de los genes expresados diferencialmente entre juveniles y adultos de la tortuga Caguama (Caretta caretta) relacionados con hipoxia y sistema inmune: primera aproximaciónIn silico analysis and identification of genes expressed differentially between juveniles and adults of the loggerhead turtle (caretta caretta) related to hypoxia and inmune system: first approachTrabajo de grado de pregradohttp://purl.org/coar/resource_type/c_46ecAfgan, E., D. Baker, B. Batut, M. van den Beek, D. Bouvier, M. Čech, J. Chilton, D. Clements, N. Coraor, B. Grüning, A. Guerler, J. Hillman-Jackson, V. Jalili, H. Rasche, N. Soranzo, J. Goecks, J. Taylor, A. Nekrutenko and D. Blankenberg. 2018. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses. Nucleic Acids Research. 46(1,2): 537-544 pAgarwal A, D. Koppstein, J. Rozowsky, A. Sboner, L. Habegger, L.W. Hillier, R. Sasidharan, V. Reinke, R.H. Waterston and M. Gerstein. 2010. Comparison and calibration of transcriptome data from RNA-Seq and tiling arrays. BMC genomics. 11(1):1 pAlvarez, M., A.W. Schrey and C.L. Richards. 2015. Ten years of transcriptomics in wild populations: what have we learned about their ecology and evolution?. Mol Ecol. 24(4):710–25 p.Andrews, S. 2018. FastQC A Quality control tool for high throughput sequence data. Babraham. Bioinfo. http://www.bioinformatics.babraham.ac.uk/projects/fastqc. 7/04/2022.Banerjee, S.M., J.A. Stoll, C.D. Allen, J.M. Lynch, H.S. Harris, L. Kenyon, R.E. Connon, E.J. Sterling, E. Naro-Maciel, K. McFadden, M.M. Lamont, J. Benge, N.B. Fernandez, J.A. Seminoff, S.R. Benson, R.L. Lewison, T. Eguchi, T.M. Summers, J.R. Hapdei, M.R. Rice, S. Martin, T. Todd, P.H. Dutton, G.H. Balazs and L.M. Komoroske. 2021. Species and population specific gene expression in blood transcriptomes of marine turtles. BMC Genomics. 22: 346 p.Bentley, B.P., B.J. Haas, J.N. Tedeschi and O. Berry. 2017. Loggerhead Sea turtle embryos (Caretta caretta) regulate expression of stress response and developmental genes when exposed to a biologically realistic heat stress. Molecular ecology. 26(11): 2978-2992 p.Block, B.A., I.D. Jonsen, S.J. Jorgensen, A.J. Winship, S.A. Shaffer and S.J. Bograd. 2011. Tracking apex marine predator movements in a dynamic ocean. Nature. 475: 86–90 p.Bolger, A.M., M. Lohse and B. Usadel. 2014. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics. PubMed. 30: 2114–2120 p.Cásale, P. and A.D. Tucker. 2017. Caretta caretta (amended version of 2015 assessment). The IUCN Red List of Threatened Species 2017: e.T3897A119333622. https://dx.doi.org/10.2305/IUC N.UK.2017-2.RLTS.T3897A119333622.en. 21/12/2021.Canada's Genomic Enterprise. 2022. Loggerhead Sea Turtle (Caretta caretta) genome sequencing and assembly (Canada's Genomic Enterprise), rCarCar2. https://www.ncbi.nlm.ni h.gov/data-hub/genome/GCF_023653815.1/. 25/10/2022.Chamorro, C. 2019. Análisis de datos de RNA-Seq empleando diferentes paquetes desarrollados dentro del proyecto Bioconductor para estudios de expresión génica diferencial. Creative Commons. 74 p.Cocci, P., M. Capriotti, G. Mosconi and F.A. Palermo. 2017. Effects of endocrine disrupting chemicals on estrogen receptor alpha and heat shock protein 60 gene expression in primary cultures of loggerhead sea turtle (Caretta caretta) erythrocytes. Environmental Research. 158: 616-624 pCocci, P., G. Mosconi, L. Bracchetti, J.M. Nalocca, E. Frapiccini, M. Marini, G. Caprioli, G. Sagratini and F.A. Palermo. 2018. Investigating the potential impact of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) on gene biomarker expression and global DNA methylation in loggerhead sea turtles (Caretta caretta) from the Adriatic Sea. Science of The Total Environment. 619–620: 49-57 p.Cocci, P., G. Mosconi and F.A. Palermo. 2022. Organic UV Filters Induce Toll-like-Receptors and Related Signaling Pathways in Peripheral Blood Mononuclear Cells of Juvenile Loggerhead Sea Turtles (Caretta caretta). Animals. 12(5): 594 p.Chow, J.C., N. Kyritsis, M. Mills, M.H. Godfrey, C.A. Harms, P.E. Anderson and A.M. Shedlock. 2021. Tissue and Temperature-Specific RNA-Seq Analysis Reveals Genomic Versatility and Adaptive Potential in Wild Sea Turtle Hatchlings (Caretta caretta). Animals. 11: 3013 pChegwidden, WR. and N.D. Carter. 2000. Introduction to the carbonic anhydrases. EXS. 90: 13-28 p.Conesa, A., S. Götz, J.M. García-Gómez, J. Terol, M. Talón and M. Robles. 2005. Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research. Bioinformatics. 21(18): 3674-3676 p.Denley, A., E.R. Bonython, G.W. Booker, L.J. Cosgrove, B.E. Forbes, C.W. Ward and J.C. Wallace. 2004. Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. Molecular Endocrinology. 18(10): 2502– 2512 p.Dolmán, A.J. 1990. “The Potential Contribution of Marine Resources to Sustainable Development in Small-Island Developing Countries”, in Beller, W., P. D'Ayala and P. Hein, (Eds), Sustainable Development and Environmental Management of Small Islands. Man and the Biosphere Series. Volume 5. UNESCO, Paris, and Parthenon Publishing Carnforth.Eckert, K.L., K.A. Bjorndal, F.A. Abreu-Grobois y M. Donnelly. 2000. Técnicas de Investigación y Manejo para la Conservación de las Tortugas Marinas. Grupo especialista en Tortugas Marinas. Unión Internacional para la Conservación de la Naturaleza y Comisión de Supervivencia de Especies. 4: 270 p.Frasca, D., A.M. Landin, R.L. Riley and B.B. Blomberg. 2008. Mechanisms for decreased function of B cells in aged mice and humans. J. Immunol. 180: 2741–2746 p.Gardner, S.C., M.D. Pier, R. Wesselman and J.A. Juarez. 2003. Organochlorine contaminants in sea turtles from the eastern Pacific. Marine Pollution Bulletin. 46: 1082-1089 p.Grings, M., M. Wajner and G. Leipnitz. 2020. Mitochondrial dysfunction and redox homeostasis impairment as pathomechanisms of brain damage in ethylmalonic encephalopathy: insights from animal and human studies. Cellular and Molecular Neurobiology. 42: 1-11 p.Guillemot, F., A. Billault, O. Pourquie, G. Behar, A.M. Chaussé, R. Zoorob, G. Kreibich and C. Auffray. 1988. A molecular map of the chicken major histocompatibility complex: the class II beta genes are closely linked to the class I genes and the nucleolar organizer. The EMBO journal. 7(9): 2775- 2785 p.Gu, Y.Z., J.B. Hogenesch and C.A. Bradfield. 2000. The PAS Superfamily: Sensors of Environmental and Developmental Signals. Annu Rev Pharmacol. 40: 519–561 p.Harman, D. 1956. Aging: A theory based on free radical and radiation chemistry. Journal of Gerontology 11: 298–300 pHawkes, L.A., A.C. Broderick, M.S. Coyne, M.H. Godfrey and B.J. Godley. 2007. Only some like it hot - quantifying the environmental niche of the loggerhead sea turtle. Divers. Distrib. 13: 447- 457Heikkilä, M., A. Pasanen, K.I. Kivirikko and J. Myllyharju. 2011. Roles of the human hypoxia inducible factor (HIF)-3α variants in the hypoxia response. Life Sciences. 68(23): 3885–3901Hernández-Fernández, J., A. Pinzón, L. and Mariño-Ramírez. 2017. De novo transcriptome assembly of loggerhead sea turtle nesting of the Colombian Caribbean. Genomics Data. 13: 18-20 p.Hernández-Fernández, J., A.M. Pinzón-Velasco, E.A. López-Barrera, M. Rodríguez-Becerra, J.L. Villanueva-Cañas, M. Alba, L. Mariño-Ramírez. 2021. De novo assembly and functional annotation of blood transcriptome of loggerhead turtle, and in silico characterization of peroxiredoxins and thioredoxins. PeerJ. 9: 32 p.Hochscheid, S., F. Bentivegna, M.N. Bradai and G.C. Hays. 2007a. Overwintering behaviour in sea turtles: dormancy is optional. Mar. Ecol. Prog. Ser. 340: 287-298 p.Hochscheid, S., C.R. McMahon, C.J.A. Bradshaw, F. Maffucci, F. Bentivegna and G.C. Hays. 2007b. Allometric scaling of lung volume and its consequences for marine turtle diving performance. Comp Biochem Physiol A. 148: 360–367 p.Hoekstra, L.A., T.S. Schwartz, A.M. Sparkman, D.A.W. Miller and A.M. Bronikowski. 2020. The untapped potential of reptile biodiversity for understanding how and why animals age. Funct Ecol. 34: 38– 54 p.Iverson, A.R., I. Fujisaki, M.M. Lamont and K.M. Hart. 2019. Loggerhead Sea turtle (Caretta caretta) diving changes with productivity, behavioral mode, and sea surface temperature. PloS one. 14(8): 19 p.Kamei, H. 2020. Oxygen and embryonic growth: the role of insulin-like growth factor signaling. General and Comparative Endocrinology. 294: 113473 pKeller, J.M., J.R. Kucklick, M.A. Stamper, C.A. Harms and P.D. McClellan-Green. 2004. Associations between organochlorine contaminant concentrations and clinical health parameters in loggerhead sea turtles from North Carolina, USA. Environ. Health Persp. 112: 1074-1079 p.Keller, J.M., P.D. McClellan-Green, A.M. Lee, M.D. Arendt, P.P. Maier, A.L. Segars, J.D. Whitaker, D.E. Keil and M.M. Peden-Adams. 2005. Mitogen-induced lymphocyte proliferation in loggerhead sea turtles: comparison of methods and effects of gender, plasma testosterone concentration, and body condition on immunity. Vet. Immunol. Immunopathol. 103: 269-281 p.Keller, J.M., P.D. McClellan-Green, J.R. Kucklick, D.E. Keil and M.M. Peden-Adams. 2006. Effects of organochlorine contaminants on loggerhead sea turtle immunity: comparison of a correlative field study and in vitro exposure experiments. Environ. Health. Persp. 114: 70-76 p.Kim, G. and R. Levine. 2005. Molecular determinants of S-glutathionylation of carbonic anhydrase 3. Antioxidants and Redox Signalling. 7: 849-854 pKim, D., B. Langmead and S.L. Salzberg. 2015. HISAT: a fast spliced aligner with low memory requirements. Nature Methods. 12(4): 357-360 p.Krivoruchko, A. and K.B. Storey. 2015. Turtle anoxia tolerance: biochemistry and gene regulation. Biochimica et Biophysica Acta (BBA)-General Subjects. 1850(6): 1188-1196 p.Kovaka, S., A.V. Zimin, G.M. Pertea, R. Razaghi, S.L. Salzberg and M. Pertea. 2019. Transcriptome assembly from long-read RNA-seq alignments with StringTie2. Genome Biology. 20(1): 1-14 p.Ku, H.H., U.T. Brunk and R.S. Sohal. 1993. Relationship between mitochondrial superoxide and hydrogen‐peroxide production and longevity of mammalian‐species. Free Radical Biology and Medicine. 15: 621–627 p.Lambert, A.J., H.M. Boysen, J.A. Buckingham, T. Yang, A. Podlutsky, S.N. Austad and M.D. Marca. 2007. Low rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms. Aging Cell. 6: 607–618 p.Lapennas, G.N. and P.L. Lutz. 1982. Oxygen affinity of sea turtle blood. Respiration physiology. 48(1): 59-74 p.Lee, J.S., W.O. Ward, D.C. Wolf, J.W. Allen, C. Mills, M.J. DeVito and J.C. Corton. 2008. Coordinated Changes in Xenobiotic Metabolizing Enzyme Gene Expression in Aging Male Rats. Toxicological Sciences. 106(1): 263-283 p.Lin, K., J.B. Dorman, A. Rodan and C. Kenyon. 1997. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science. 278(5341): 1319- 1322 p.Li, G.X., Y. Hirabayashi, B.I. Yoon, Y. Kawasaki, I. Tsuboi, Y. Kodama, Y. Kurokawa, J. Yodoi, J. Kanno and T. Inoue. 2006. Thioredoxin overexpression in mice, model of attenuation of oxidative stress, prevents benzene-induced hemato-lymphoid toxicity and thymic lymphoma. Exp Hematol. 34(12): 1687-1697 p.Li, C., L. Song, J. Zhao, L. Zhu, H. Zou, H. Zhang, H. Wang and Z. Cai. 2007. Preliminary study on a potential antibacterial peptide derived from histone H2A in hemocytes of scallop Chlamys farreri. Fish & Shellfish Immunology. 22(6): 663-672 p.Li, H., B. Handsaker, A. Wysoker, T. Fennell, J. Ruan, N. Homer, G. Marth, G. Abecasis and R. Durbin. 2009. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 25(16): 2078- 2079 p.Liao, Y., G.K. Smyth and W. Shi. 2014. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 30(7): 923-930 p.Love, M.I., W. Huber and S. Anderson. 2014. Moderated estimation of fold changes and dispersion of RNA-Seq data with DESeq. Genome Biol. 15(12): 550 p.Lutz, P.L. and T.B. Bentley. 1985. Respiratory Physiology of Diving in the Sea Turtle. Copeia. 1985(3): 671–679 pLutcavage, M.E., P.G. Bushnell and D.R. Jones. 1990. Oxygen transport in the leatherback sea turtle Dermochelys coriacea. Physiol. Zool. 63: 1012-1024 p.Lukacs, M.F., H. Harstad, U. Grimholt, M. Beetz-Sargent, G.A. Cooper, L. Reid, H.G. Bakke, R.B. Phillips, K.M. Miller, W.S. Davidson and B.F. Koop. 2007. Genomic organization of duplicated major histocompatibility complex class I regions in Atlantic salmon (Salmo salar). BMC genomics. 8(1): 1-16 p.Marco, A., C. Carreras y E. Abella. 2008. Tortuga boba – Caretta caretta. En: Enciclopedia Virtual de los Vertebrados Españoles. Carrascal, L. M., Salvador, A. (Eds.). Museo Nacional de Ciencias Naturales, Madrid. http://www.vertebradosibericos.org/.Marzio, R., J. Mauël and S. Betz-Corradin. 1999. CD69 and Regulation of the Immune Function. Immunopharmacology and Immunotoxicology. 21(3): 565-582 p.Mayne, B., A.D. Tucker, O. Berry y S. Jarman. 2020. Lifespan estimation in marine turtles using genomic promoter CpG density. Plos one. 15(7): 1-8 p.McDermaid, A., B. Monier, J. Zhao, B. Liu and Q. Ma. 2019. Interpretation of differential gene expression results of RNA-seq data: review and integration. Briefings in bioinformatics. 20: 2044–2054 p.Metzker, M.L. 2010. Sequencing technologies - the next generation. Nature reviews Genetics. 11(1): 31-46 p.Milton, S.L. 1994. The physiology of hypoxia and anoxia tolerance in three species of turtle: the loggerhead sea turtle (Caretta caretta), green sea turtle (Chelonia mydas), and freshwater Trachemys scripta. University of Miami. 175 p.Mu, Y., W. Li, Z. Wei, L. He, W. Zhang and X. Chen. 2020. Transcriptome analysis reveals molecular strategies in gills and heart of large yellow croaker (Larimichthys crocea) under hypoxia stress. Fish & shellfish immunology. 104: 304-313 p.Nath, A.K., J. Ma, Z.Z. Chen, Z. Li, M.D.C. Vitery, M.L. Kelley, R.T. Peterson, R.E. Gerszten and J.J. Yeh. 2020. Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish. The FASEB Journal. 34(1): 1546-1557 p.Niu, N., D.J. Schaid, R.P Abo, K. Kalari, B.L. Fridley, Q. Feng, G. Jenkins, A. Batzler, A.G. Brisbin, J.M. Cunningham, L. Li, Z. Sun, P. Yang and L. Wang. 2012. Genetic association with overall survival of taxane-treated lung cancer patients -a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study. BMC cancer. 12(1): 1-13 p.Ogg, S., S. Paradis, S. Gottlieb, G.I. Patterson, L. Lee, H.A. Tissenbaum, and G. Ruvkun. 1997. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 389: 994-999 pOlson, K.R., J.A. Donald, R.A. Dombkowski and S.F. Perry. 2012. Evolutionary and comparative aspects of nitric oxide, carbon monoxide and hydrogen sulfide. Respiratory physiology & neurobiology. 184(2): 117-129 p.Ozsolak, F. and P.M. Milos. 2011. RNA sequencing: advances, challenges, and opportunities. Nature Rev. Genet. 12: 87–98 p.Pappworth, I.Y., C. Hayes, J. Dimmick, B.P. Morgan, V.M. Holers and K.J. Marchbank. 2012. Mice expressing human CR1/CD35 have an enhanced humoral immune response to T-dependent antigens but fail to correct the effect of premature human CR2 expression. Immunobiology. 217(2): 147-157 p.Potter, C. and A.L. Harris. 2004. Hypoxia inducible carbonic anhydrase IX, marker of tumor: hypoxia, survival pathway and therapy target. Cell cycle. 3(2): 159-162 p.Quesada, V., S. Freitas-Rodríguez, J. Miller, J.G. Pérez-Silva, Z.F. Jiang, W. Tapia and C. López-Otín. 2019. Giant tortoise genomes provide insights into longevity and age-related disease. Nature ecology & evolution. 3(1): 87-95 p.Raymond, W., N.A. Vo and A. Kiyoshi. 2012. Transformations for the compression of FASTQ quality scores of next-generation sequencing data. Bioinformatics. 28(5): 628–635 p.Ritchie, M.E., B. Phipson, D. Wu, Y. Hu, C.W Law y W. Shi. 2015. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic acids research. 43(7): 47 p.Robinson, M.D., D.J. McCarthy and G.K. Smith. 2010. EdgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 26(1): 40-139 p.Rousselet, E., M. Levin, E. Gebhard, B.M. Higgins, S. DeGuise and C.A. Godard-Codding. 2013. Evaluation of immune functions in captive immature loggerhead sea turtles (Caretta caretta). Veterinary Immunology and Immunopathology. 156(1-2): 43-53 p.Robin, J.D., A.T. Ludlow, R. LaRanger, W.E. Wright and J.W. Shay. 2016. Comparison of DNA quantification methods for next generation sequencing. Scientific reports. 6(1): 1-10 p.Sancho, D., M. Gómez and F. Sánchez-Madrid. 2005. CD69 is an immunoregulatory molecule induced following activation. Trends in immunology. 26(3): 136-140 p.Schmidt, E. and H. Knackmuss. 1980. Chemical structure and biodegradability of halogenated aromatic compounds. Conversion of chlorinated muconic acids into maleoylacetic acid. Biochemical Journal. 192(1): 339-347 p.Schwartz, T.S. and A.M. Bronikowski. 2016. Evolution and function of the insulin and insulin like signaling network in ectothermic reptiles: some answers and more questions. Integrative and Comparative Biology. 56(2): 171-184 p.Seim, I., X. Fang, Z. Xiong, A.V. Lobanov, Z. Huang, S. Ma and V.N. Gladyshev. 2013. Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii. Nature communications. 4(1): 1-8 p.Shiina, T., H. Inoko and J.K. Kulski. 2004. An update of the HLA genomic region, locus information and disease associations. Tissue Antigens. 64: 631-649 p.Silagi, E.S., P. Batista, I.M. Shapiro and M.V. Risbud. 2018. Expression of carbonic anhydrase III, a nucleus pulposus phenotypic marker, is hypoxia-responsive and confers protection from oxidative stress-induced cell death. Scientific Reports. 8(1): 1-13 p.Sparkman, A.M., T.S. Schwartz, J.A. Madden, S.E. Boyken, N.B. Ford, J.M. Serb and A.M. Bronikowski. 2012. Rates of molecular evolution vary in vertebrates for insulin-like growth factor-1 (IGF-1), a pleiotropic locus that regulates life history traits. General and comparative endocrinology. 178(1): 164-173 p.Speakman, J.R., J.D. Blount, A.M. Bronikowski, R. Buffenstein, C. Isaksson, T.B.L. Kirkwood and C. Selman. 2015. Oxidative stress and life histories: Unresolved issues and current needs. Ecology and Evolution. 5: S745–S757 p.Steinmann, G.G. 1986 Changes in the human thymus during aging. Curr. Top.. Pathol. 75: 43-Storey, K.B. 2007. Anoxia tolerance in turtles: Metabolic regulation and gene expression. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. 147(2): 263- 276 p.Stutte, S., T. Quast, N. Gerbitzki, T. Savinko, N. Novak, J. Reifenberger, B. Homey, W. Kolanus, H. Alenius and I. Forster. 2010. Requirement of CCL17 for CCR7- and CXCR4-dependent migration of cutaneous dendritic cells. Proceedings of the National Academy of Sciences. 107(19): 8736-8741 p.Supuran, C.T. 2016. Structure and function of carbonic anhydrases. Biochem. J. 473: 2023– 2032 p.Su, S., C.W. Law, C. Ah-Cann, M.L. Asselin-Labat, M.E. Blewitt and M.E. Ritchie. 2017. Glimma: interactive graphics for gene expression analysis. Bioinformatics. 33(13): 2050-2052 p.Thankaswamy-Kosalai, S., P. Sen and I. Nookaew. 2017. Evaluation and assessment of read mapping by multiple next-generation sequencing aligners based on genome-wide characteristics. Genomics. 109(3-4): 186-191 p.Tenney, S.M., D. Bartlett, J.P Farber and J.E. Remmers. 1974. Mechanics of the respiratory cycle in the green turtle (Chelonia mydas). Respiration physiology. 22(3): 361-368 pTeelucksingh, S., S. Eckert and P. Nunes. 2010. Marine turtles, ecosystem services and human welfare in the marine ecosystems of the Caribbean Sea: a discussion of key methodologies. Études caribéennes. 15: 2–14 p.Ujvari, B. and T. Madsen. 2011. Do natural antibodies compensate for humoral immunosenescence in tropical pythons?. Funct. Ecol. 25: 813–817 p.van Dam R.P. and C.E. Diez. 1997. Diving behavior of immature hawksbills (Eretmochelys imbricata) in a Caribbean reef habitat. Coral Reefs. 16:133–138 p.Wang, Z., M. Gerstein and M. Snyder. 2009. RNA-seq: a revolutionary tool for transcriptomics. Nature Rev. Genet. 10: 57–63 p.Wu, D. and S.N. Meydani. 2008. Age‐associated changes in immune and inflammatory responses: impact of vitamin E intervention. Journal of leukocyte biology. 84(4): 900-914 p.Wykoff, C.C., N.J. Beasley, P.H. Watson, K.J. Turner, J. Pastorek, A. Sibtain, G.D. Wilson, H. Turley, K.L. Talks, P.H. Maxwell, C.W. Pugh, P.J. Ratcliffe and AL. Harris. 2000. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res. 60:7075–7083 p.Yu, Y., J.C. Fuscoe, C. Zhao, C. Guo, M. Jia, T. Qing, D.I. Bannon, L. Lancashire, W. Bao, T. Du, H. Luo, Z. Su, W.D. Jones, C.L. Moland, W.S. Branham, F. Qian, B. Ning, Y. Li, H. Hong, L. Guo, N. Mei, T. Shi, K.Y. Wang, R.D. Wolfinger and C. Wang. 2014. A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nature communications. 5(1): 1-11 p.Zhang, G., J. Zhang, X. Wen, C. Zhao, H. Zhang, X. Li and S. Yin. 2017. Comparative iTRAQ‐ Based Quantitative Proteomic Analysis of Pelteobagrus vachelli Liver under Acute Hypoxia: Implications in Metabolic Responses. Proteomics. 17: 17-18 p.Zimmerman, L.M., G.S. Clairardin, R.T. Paitz, J.W. Hicke, K.A. LaMagdeleine, L.A. Vogel and R.M. Bowden. 2013. Humoral immune responses are maintained with age in a long-lived ectotherm, the red-eared slider turtle. Journal of Experimental Biology. 216(4): 633-640 pZmienko, A., P. Jackowiak and M. Figlerowicz. 2011. Transcriptome sequencing: next generation approach to RNA functional analysis. BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology. 92(4): 311-319 pTHUMBNAILRivera-Forero Catalina Tesis_2023.pdf.jpgRivera-Forero Catalina Tesis_2023.pdf.jpgIM Thumbnailimage/jpeg6364https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/31047/6/Rivera-Forero%20Catalina%20Tesis_2023.pdf.jpg521bcfe28949358f545edb9133bbbdc7MD56open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-82938https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/31047/2/license.txtbaba314677a6b940f072575a13bb6906MD52open accessPermiso de publicación tesis.pdfPermiso de publicación tesis.pdfapplication/pdf627875https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/31047/4/Permiso%20de%20publicaci%c3%b3n%20tesis.pdf634efe5537aa3296497da87b3b00e62fMD54open accessORIGINALRivera-Forero Catalina Tesis_2023.pdfRivera-Forero Catalina Tesis_2023.pdfDocumento reservado / Confidential documentapplication/pdf1289432https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/31047/7/Rivera-Forero%20Catalina%20Tesis_2023.pdf41c6743359c96c37efc0d2c7f4921879MD57embargoed access|||2025-02-0120.500.12010/31047oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/310472024-05-13 08:37:05.047embargoed access|||2025-02-01Repositorio Institucional - Universidad Jorge Tadeo Lozanoexpeditiorepositorio@utadeo.edu.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 |