Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico

ilustraciones

Autores:
Rodríguez Alvarino, Paula Estefanía
Tipo de recurso:
Fecha de publicación:
2023
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/84751
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/84751
https://repositorio.unal.edu.co/
Palabra clave:
610 - Medicina y salud::616 - Enfermedades
Secuenciación Completa del Genoma
Predisposición Genética a la Enfermedad
Enfermedades Genéticas Congénitas
Whole Genome Sequencing
Genetic Predisposition to Disease
Genetic Diseases, Inborn
Secuenciación del exoma completo
Diagnóstico
NGS
Pruebas genéticas
Genética
Fenotipo
Diagnostics
NGS
Exome sequencing
Genetic testing
Genomics
Phenotype
Rights
openAccess
License
Atribución-NoComercial-CompartirIgual 4.0 Internacional
id UNACIONAL2_9ec43308c507e10a2ff622b759973df9
oai_identifier_str oai:repositorio.unal.edu.co:unal/84751
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico
dc.title.translated.eng.fl_str_mv Diagnostic yield of trio and individual Whole Exome Sequencing in a group of Colombian patients with a suspected monogenic disease
title Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico
spellingShingle Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico
610 - Medicina y salud::616 - Enfermedades
Secuenciación Completa del Genoma
Predisposición Genética a la Enfermedad
Enfermedades Genéticas Congénitas
Whole Genome Sequencing
Genetic Predisposition to Disease
Genetic Diseases, Inborn
Secuenciación del exoma completo
Diagnóstico
NGS
Pruebas genéticas
Genética
Fenotipo
Diagnostics
NGS
Exome sequencing
Genetic testing
Genomics
Phenotype
title_short Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico
title_full Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico
title_fullStr Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico
title_full_unstemmed Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico
title_sort Rendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénico
dc.creator.fl_str_mv Rodríguez Alvarino, Paula Estefanía
dc.contributor.advisor.spa.fl_str_mv Gálvez Bermúdez, Jubby Marcela
Ospina Lagos, Sandra Yaneth
dc.contributor.author.spa.fl_str_mv Rodríguez Alvarino, Paula Estefanía
dc.subject.ddc.spa.fl_str_mv 610 - Medicina y salud::616 - Enfermedades
topic 610 - Medicina y salud::616 - Enfermedades
Secuenciación Completa del Genoma
Predisposición Genética a la Enfermedad
Enfermedades Genéticas Congénitas
Whole Genome Sequencing
Genetic Predisposition to Disease
Genetic Diseases, Inborn
Secuenciación del exoma completo
Diagnóstico
NGS
Pruebas genéticas
Genética
Fenotipo
Diagnostics
NGS
Exome sequencing
Genetic testing
Genomics
Phenotype
dc.subject.decs.spa.fl_str_mv Secuenciación Completa del Genoma
Predisposición Genética a la Enfermedad
Enfermedades Genéticas Congénitas
dc.subject.decs.eng.fl_str_mv Whole Genome Sequencing
Genetic Predisposition to Disease
Genetic Diseases, Inborn
dc.subject.proposal.spa.fl_str_mv Secuenciación del exoma completo
Diagnóstico
NGS
Pruebas genéticas
Genética
Fenotipo
dc.subject.proposal.eng.fl_str_mv Diagnostics
NGS
Exome sequencing
Genetic testing
Genomics
Phenotype
description ilustraciones
publishDate 2023
dc.date.accessioned.none.fl_str_mv 2023-10-03T20:18:08Z
dc.date.available.none.fl_str_mv 2023-10-03T20:18:08Z
dc.date.issued.none.fl_str_mv 2023
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/84751
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.none.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/84751
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.indexed.spa.fl_str_mv Bireme
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spelling Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Gálvez Bermúdez, Jubby Marcela203b46e3eecd4ceda2e147a0ccc96f76Ospina Lagos, Sandra Yaneth16b77c264a0d10629b62301adacc6e8eRodríguez Alvarino, Paula Estefanía5cb05ed1bf12de1063f117096aae70f22023-10-03T20:18:08Z2023-10-03T20:18:08Z2023https://repositorio.unal.edu.co/handle/unal/84751Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustracionesDurante los últimos años, la secuenciación del exoma completo ha tenido una gran aceptación para la evaluación de trastornos genéticos. Gracias al acceso a la secuenciación de siguiente o nueva generación (NGS), a las herramientas bioinformáticas y a los expertos profesionales, estas pruebas moleculares representan una herramienta diagnóstica de primera línea para muchas enfermedades genéticas. El objetivo de este estudio fue determinar el rendimiento diagnóstico de la secuenciación de exoma en trio e individual en un grupo de pacientes colombianos con sospecha clínica de enfermedad genética monogénica, así como el rendimiento diagnóstico por grupos de fenotipos, entre junio de 2020 y mayo de 2021. Se realizó un estudio descriptivo transversal, retrospectivo, aprobado por el comité de ética en investigación. Se revisaron las historias clínicas para obtener los datos clínicos y fenotípicos, y se realizó secuenciación de exoma completo en trio. El llamado de variantes se realizó utilizando las mejores prácticas de GATK, con la posterior anotación y filtrado utilizando términos de Human Phenotype Ontology (HPO) y las variantes se clasificaron utilizando las directrices del Colegio Americano de Genética Médica y Genómica (ACMG, por sus siglas en inglés) de 2015. Se realizaron análisis tanto de exoma individual como análisis de exoma en trio en cada caso. Los casos se consideraron positivos cuando se identificaron variantes patogénicas (P) o probablemente patogénicas (PP), con un mecanismo de herencia que explicaba el fenotipo del paciente. Además, los casos se estratificaron por grupos según el fenotipo clínico, para evaluar el rendimiento específico de la prueba. Se incluyeron un total de 100 casos. La edad media fue de 8.6 años, y siete casos eran hijos de padres consanguíneos. El rendimiento diagnóstico fue del 29% para el análisis de exomas únicos y del 32% para el análisis en trio. Entre los casos positivos, el 19% presentaba una enfermedad autosómica dominante, el 8% una enfermedad ligada al cromosoma X, el 4% una enfermedad autosómica recesiva y el 1% un trastorno de herencia digénica. Dos casos tenían hallazgos incidentales en los genes PMS2 y MSH6, y otros dos casos tenían condiciones monogénicas concomitantes. El fenotipo más prevalente fue el retraso del neurodesarrollo en el 47% de los individuos, con un rendimiento del 38.3%. El mayor rendimiento se encontró en la parálisis (71.3%), seguido de la hipoacusia (55.5%), la microcefalia (50%), la hipertensión pulmonar (50%) y las alteraciones hematológicas (50%). Los movimientos anormales tuvieron la tasa de diagnóstico más baja (10%). Este estudio mostró un rendimiento 3% mayor para el análisis del exoma en trío en comparación con el individual. Esto se explica principalmente por la identificación de variantes de novo y mutaciones heterocigotas compuestas confirmadas, que no pueden establecerse en los exomas únicos. El exoma trio mostró el mejor rendimiento en los fenotipos neurológicos, especialmente en individuos con parálisis. (Texto tomado de la fuente).During last years, Whole Exome Sequencing (WES) has had great acceptance for the evaluation of genetic disorders. Due to the access to next-generation sequencing (NGS), bioinformatics tools, and professionals’ experts, these molecular tests represent a first- tier diagnostic tool for many genetic diseases. The aim was to compare the diagnostic yield of singleton and trio WES in a Colombian cohort with clinical suspicion of a genetic disease, as well as the yield per phenotype groups, between June 2020 to May 2021. A cross-sectional descriptive, retrospective study, approved by an ethics board, was carried out. Medical records were reviewed to obtain phenotypic data and trio WES was performed. Variant calling was done using GATK best practices, with subsequent annotation and filtering using Human Phenotype Ontology (HPO) terms and variants were classified using the American College of Medical Genetics and Genomics (ACMG) 2015 guidelines. Analysis as singleton exome and trio exome were performed for every case. Cases were considered positive when pathogenic (P) or likely pathogenic (PP) variants were identified, with a mechanism of inheritance explaining the patient’s phenotype. Additionally, cases were stratified by groups according to the main clinical phenotype, to evaluate the specific yield of the test. A total of 100 cases were included. The average age was of 8.6 years, and seven cases were born of consanguineous parents. The diagnostic yield was 29% for singleton and 32% for trio WES. Among positive cases, 19% had an autosomal dominant disease, 8% an X-linked, 4% autosomal recessive, and 1% a digenic inheritance disorder. Two cases had incidental findings in PMS2 and MSH6 genes, and two other cases had concomitant monogenic conditions. The most prevalent phenotype was neurodevelopmental delay in 47% individuals, with a yield of 38.3%. The highest yield was found for paralysis (71.3%), followed by hypoacusis (55.5%), microcephaly (50%), pulmonary hypertension (50%) and hematologic alterations (50%). Abnormal movements had the lowest diagnostic rate (10%). This study showed a 3% better yield for trio exome analysis in comparison to singleton. This is mainly explained by the identification of de novo variants and confirmed compound heterozygous mutations, which cannot be established in singleton exomes. WES showed the best performance in neurological phenotypes, especially paralysis.MaestríaMagíster en Genética HumanaGenética clínicaxviii, 110 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en Genética HumanaFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::616 - EnfermedadesSecuenciación Completa del GenomaPredisposición Genética a la EnfermedadEnfermedades Genéticas CongénitasWhole Genome SequencingGenetic Predisposition to DiseaseGenetic Diseases, InbornSecuenciación del exoma completoDiagnósticoNGSPruebas genéticasGenéticaFenotipoDiagnosticsNGSExome sequencingGenetic testingGenomicsPhenotypeRendimiento diagnóstico de la secuenciación de exomas completos en trio e individual en una cohorte de pacientes colombianos con sospecha de enfermedad genética de origen monogénicoDiagnostic yield of trio and individual Whole Exome Sequencing in a group of Colombian patients with a suspected monogenic diseaseTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMBiremeDurmaz AA, Karaca E, Demkow U, Toruner G, Schoumans J, Cogulu O. 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European Journal of Human Genetics. el 1 de noviembre de 2018;26(11):1566–71.EstudiantesInvestigadoresMaestrosPúblico generalTHUMBNAIL1032459981.Tesis.pdf.jpg1032459981.Tesis.pdf.jpgGenerated Thumbnailimage/jpeg5822https://repositorio.unal.edu.co/bitstream/unal/84751/5/1032459981.Tesis.pdf.jpgf3ee223db3d89a1102135fd55cb1ca6fMD55ORIGINAL1032459981.Tesis.pdf1032459981.Tesis.pdfTesis de Maestría en Genética Humanaapplication/pdf1530976https://repositorio.unal.edu.co/bitstream/unal/84751/4/1032459981.Tesis.pdfcf3d04062d285d768fd1acd8d1774e36MD54LICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/84751/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51unal/84751oai:repositorio.unal.edu.co:unal/847512023-10-17 23:04:06.89Repositorio Institucional Universidad Nacional de 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