Análisis de la secuencia del genoma humano en pacientes con sospecha de enfermedad monogénica empleando tecnologías de secuenciación de nueva generación implementadas en Colombia

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dc.contributor.advisorBello Uyaban, Sandra Patriciaspa
dc.contributor.advisorRey Buitrago, Mauriciospa
dc.contributor.authorChavarro Moreno , Diego Alexanderspa
dc.contributor.researchgroupGenuino Gencell – Genética Clínica UNALspa
dc.coverage.countryColombiaspa
dc.coverage.tgnhttp://vocab.getty.edu/page/tgn/1000050
dc.date.accessioned2025-09-17T21:32:19Z
dc.date.available2025-09-17T21:32:19Z
dc.date.issued2025-09-16
dc.descriptionilustraciones, diagramas, fotografías, mapasspa
dc.description.abstractObjetivo. La presente investigación pretendió caracterizar las variantes genéticas y la relación genotipo fenotipo en una corte de pacientes con sospecha clínica de enfermedad monogénica mediante el análisis del genoma completo empleando tecnologías de secuenciación de siguiente generación implementadas en Colombia. Metodología. Este estudio es de tipo transversal observacional de tipo descriptivo en una corte de 106 pacientes recibidos en el laboratorio de referencia de Gencell sede Bogotá entre el periodo 2023 – 2024 bajo la solicitud médica para el análisis del genoma completo por la alta sospecha de enfermedad monogénica no diagnosticada mediante técnicas convencionales. La metodología incluyó la extracción de ácidos nucleicos, preparación de librerías de MGI, secuenciación en la plataforma DNBSeqT7 de MGI y el análisis bioinformático y clínico de las variantes patogénicas y probablemente patogénicas identificadas. La misma metodología fue aplicada a controles de referencia y muestras previamente caracterizadas para validar la plataforma de secuenciación y respaldar la calidad de los hallazgos diagnósticos. Resultados. Se identificaron un total de 11 variantes clasificadas como patogénicas (18.18%) y probablemente patogénicas (81.81%) en el 9.43% de los casos, estas variantes fueron de tipo Missense (36.36%), Frameshift (36.36%), Nonsense (9.09%) y de sitio canónico del splicing (18.18%); las variantes identificadas permitieron el diagnóstico de los síndromes de estomatocitosis hereditaria, deficiencia primaria de carnitina, ataxia espinocerebelosa tipo 42, síndrome cardio-urogenital, síndrome de Axenfeld – Reiger, síndrome ZTTK, pseudohipoaldosteronismo tipo IIE, retinitis pigmentosa y encefalopatía epiléptica y del desarrollo tipo VIB. Los resultados obtenidos se encuentran respaldados por el proceso de validación de la plataforma de secuenciación DNBSeqT7. Conclusión. Este estudio permitió el diagnóstico de 10 pacientes con sospecha clínica de enfermedad monogénica no diagnosticados mediante otras pruebas diferentes al análisis del genoma completo, demostrando su utilidad como herramienta diagnóstica integral para el diagnóstico de enfermedades monogénicas que cursan con fenotipos complejos en los cuales su aplicación contribuiría a reducir los tiempos de odisea diagnostica y aportará al desarrollo de la medicina personalizada y de precisión. (Texto tomado de la fuente).spa
dc.description.abstractObjective. This research aimed to characterize genetic variants and the genotype-phenotype relationship in a cohort of patients with suspected monogenic diseases through whole-genome analysis using next-generation sequencing technologies implemented in Colombia. Methodology. This study is a descriptive, observational, cross-sectional analysis of a cohort of 106 patients received at the Gencell reference laboratory in Bogotá between 2023 and 2024, under medical request for whole-genome analysis due to high suspicion of undiagnosed monogenic diseases using conventional techniques. The methodology included nucleic acid extraction, preparation of MGI libraries, sequencing on the MGI DNBSeq-T7 platform, and bioinformatic and clinical analysis of the pathogenic and likely pathogenic variants identified. The same methodology was applied to reference controls and previously characterized samples to validate the sequencing platform and support the quality of diagnostic findings. Results. A total of 11 variants classified as pathogenic (18.18%) and likely pathogenic (81.81%) were identified in 9.43% of the cases. These variants included missense (36.36%), frameshift (36.36%), nonsense (9.09%), and canonical splicing site (18.18%) mutations. The identified variants enabled the diagnosis of syndromes such as hereditary stomatocytosis, primary carnitine deficiency, spinocerebellar ataxia type 42, cardio-urogenital syndrome, Axenfeld-Rieger syndrome, ZTTK syndrome, pseudohypoaldosteronism type IIE, retinitis pigmentosa, and epileptic encephalopathy and developmental type VIB. The results are supported by the validation process of the DNBSeq-T7 sequencing platform. Conclusion. This study allowed the diagnosis of 10 patients with suspected monogenic diseases who had not been diagnosed through other tests apart from whole-genome analysis, demonstrating its utility as a comprehensive diagnostic tool for monogenic diseases presenting with complex phenotypes. Its application would contribute to reducing diagnostic odyssey times and advance the development of personalized and precision medicine.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Genética Humanaspa
dc.description.researchareaGenética clínicaspa
dc.format.extent119 páginasspa
dc.format.mimetypeapplication/pdf
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/88889
dc.language.isospa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Medicinaspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Medicina - Maestría en Genética Humanaspa
dc.relation.indexedBiremespa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.licenseAtribución-NoComercial 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subject.ddc610 - Medicina y salud::611 - Anatomía humana, citología, histologíaspa
dc.subject.decsGenomaspa
dc.subject.decsGenomeeng
dc.subject.decsFenotipospa
dc.subject.decsPhenotypeeng
dc.subject.decsGenotipospa
dc.subject.decsGenotypeeng
dc.subject.proposalEnfermedad monogénicaspa
dc.subject.proposalAnálisis del genoma completospa
dc.subject.proposalSecuenciación de siguiente generación (NGS)spa
dc.subject.proposalVariantes genéticasspa
dc.subject.proposalFenotipos complejosspa
dc.subject.proposalOdisea diagnósticaspa
dc.subject.proposalDiagnóstico molecularspa
dc.subject.proposalRelación genotipo – fenotipo.spa
dc.subject.proposalMonogenic diseaseeng
dc.subject.proposalWhole-genome analysiseng
dc.subject.proposalNext-generation sequencing (NGS)eng
dc.subject.proposalGenetic variantseng
dc.subject.proposalComplex phenotypeseng
dc.subject.proposalDiagnostic odysseyeng
dc.subject.proposalMolecular diagnosiseng
dc.subject.proposalGenotype-phenotype relationshipeng
dc.titleAnálisis de la secuencia del genoma humano en pacientes con sospecha de enfermedad monogénica empleando tecnologías de secuenciación de nueva generación implementadas en Colombiaspa
dc.title.translatedAnalysis of the human genome sequence in patients with suspected monogenic disease using next-generation sequencing technologies implemented in Colombiaeng
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.redcolhttp://purl.org/redcol/resource_type/TM
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dcterms.audience.professionaldevelopmentPúblico generalspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2

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Tesis de Maestría en Genética Humana
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Maestría en Genética Humana